1 NO. 90-CI-6033            JEFFERSON CIRCUIT COURT
                                    DIVISION ONE (1)
 2 
   
 3 
   JOYCE FENTRESS, ET AL.                 PLAINTIFFS
 4 
   
 5 VS.
                DEPOSITION FOR PLAINTIFFS
 6 
   
 7 SHEA COMMUNICATIONS, ET AL.            DEFENDANTS
   
 8                 * * * * * * * * * *
   
 9 
   
10 DEPONENT:    JAMES G. KOTSANOS
   
11 
   DATE:        AUGUST 16, 1993
12 
   
13 
                   * * * * * * * * * *
14 
   
15 
   
16 REPORTER:     KATHY NOLD
   
17 
   
18                KENTUCKIANA REPORTERS
                        SUITE 260
19                730 WEST MAIN STREET
               LOUISVILLE, KENTUCKY  40202
20                   (502) 589-2273

                                                 Page 1

 1 
                   * * * * * * * * * *
 2 
   
 3            UNITED STATES DISTRICT COURT
              SOUTHERN DISTRICT OF INDIANA
 4                INDIANAPOLIS DIVISION
   
 5 IN RE ELI LILLY AND COMPANY  )
     Prozac Products Liability  )  MDL Docket No. 907
 6   Litigation                 )
   
 7                 * * * * * * * * * *
   
 8                   NO. 91-02496-A
   
 9 JACKIE LYNN BIFFLE, ET AL  )  IN THE DISTRICT
                              )  COURT OF
10 V.                         )  DALLAS COUNTY, TEXAS
                              )
11 ELI LILLY & COMPANY AND    )  14TH JUDICIAL
   DISTA PRODUCTS COMPANY     )  DISTRICT
12 
                   * * * * * * * * * *
13 
                     NO. 92-14775-E
14 
   RICHARD HAROLD CROSSETT, JR.,       ) IN THE
15 CHAD H. CROSSETT, AMY MICHELLE      ) DISTRICT
   CROSSETT AND KRISTEN ANN CROSSETT,  ) COURT OF
16 INDIVIDUALLY AND AS SURVIVORS OF    )
   AND ON BEHALF OF THE ESTATE OF      )
17 JOCQUETTA ANN CROSSETT, DECEASED    )
                                       )
18 V.                                  ) DALLAS COUNTY,
                                       ) TEXAS
19 ELI LILLY & COMPANY, DISTA          )
   PRODUCTS COMPANY, TEXAS             )
20 PSYCHIATRIC COMPANY, INC.           )
   D/B/A/ HCA WILLOW PARK              ) 101ST JUDICIAL
21 HOSPITAL, JAMES K. WITSCHY, M.D.,   ) DISTRICT
   AND DOUG BELLAMY, ED.D.             )

                                                 Page 2

 1 
                   * * * * * * * * * *
 2 
                     NO. A-921,405-C
 3 
   MARIA GUADALUPE REVES               ) IN THE
 4 INDIVIDUALLY AND AS NEXT            ) DISTRICT COURT
   FRIEND OF GRANT JULIAN REVES        ) OF
 5 A MINOR CHILD, AND ON BEHALF        )
   OF THE ESTATE OF CHRISTIAN          )
 6 MARIE REVES, DECEASED               )
                                       ) ORANGE COUNTY,
 7 V.                                  ) TEXAS
                                       )
 8 ELI LILLY & COMPANY, DISTA          )
   PRODUCTS COMPANY, RAVIKUMAR         )
 9 KANNEGANTI, M.D., HOSPITAL          )
   CORPORATION OF AMERICA, A           )
10 TENNESSEE CORPORATION, HEALTH       )
   SERVICES ACQUISITION CORP.,         )
11 A DELAWARE CORPORATION,             )
   HCA PSYCHIATRIC COMPANY, A          )
12 DELAWARE CORPORATION, TEXAS         )
   PSYCHIATRIC CO., INC.. A/K/A        )
13 AND/OR D/B/A HCA BEAUMONT           )
   NEUROLOGICAL HOSPITAL, AND HCA      )
14 HEALTH SERVICES OF TEXAS, INC.      ) 128TH JUDICIAL
   A/K/A AND/OR BEAUMONT               ) DISTRICT
15 NEUROLOGICAL HOSPITAL               )
   
16                 * * * * * * * * * *

                                                 Page 3

 1 
           IN THE UNITED STATES DISTRICT COURT
 2          FOR THE WESTERN DISTRICT OF TEXAS
                  SAN ANTONIO DIVISION
 3 
   ELIZABETH T. SANCHEZ,          )
 4 INDIVIDUALLY AND AS THE        )
   SURVIVING SPOUSE, MARGARET R.  )
 5 SANCHEZ, INDIVIDUALLY AND NEXT )
   OF FRIEND OF DEBRA JEAN        )
 6 SANCHEZ, VERONICA MARIE        )
   SANCHEZ, EDWARDO ESTEBAN       )
 7 SANCHEZ, AND MICHAEL ANTHONY   )
   SANCHEZ, CHILDREN; AND ALL ON  )
 8 BEHALF OF THE ESTATE OF        )
   EDWARDO SANCHEZ                )
 9                                )
   V.                             ) CIVIL ACTION NO.
10                                ) SA93CA367
   ELI LILLY AND COMPANY AND      )
11 DISTA PRODUCTS COMPANY         )
   
12                 * * * * * * * * * *
   
13         IN THE UNITED STATES DISTRICT COURT
           FOR THE SOUTHERN DISTRICT OF TEXAS
14                  HOUSTON DIVISION
   
15 MARIA SANCHEZ, INDIVIDUALLY    )
   AND AS NEXT FRIEND OF DEBORAH  )
16 SANCHEZ, VERONICA SANCHEZ,     )
   EDDIE SANCHEZ, AND MICHAEL     )
17 SANCHEZ, AND ON BEHALF OF THE  )
   ESTATE OF EDUARDO SANCHEZ      )
18                                )
   V.                             ) CIVIL ACTION NO.
19                                ) H-93-1469
   ELI LILLY AND COMPANY AND      )
20 DISTA PRODUCTS COMPANY, A      )
   DIVISION OF ELI LILLY AND      )
21 COMPANY                        )

                                                 Page 4

 1 
                   * * * * * * * * * *
 2 
   STATE OF NEW YORK
 3 
   SUPREME COURT        COUNTY OF JEFFERSON
 4 _____________________________________________
   
 5 STEPHANIE CAPONE, AS EXECUTOR OF THE
   ESTATE OF JOSEPH J. CAPONE, JR., AND
 6 STEPHANIE CAPONE, INDIVIDUALL,
                                     NOTICE TO TAKE
 7                   PLAINTIFF,      DEPOSITION UPON
                                     ORAL EXAMINATION
 8 
           VS.                       INDEX NO. 93-251
 9 
   ELI LILLY AND COMPANY, DISTA PRODUCTS
10 COMPANY, A DIVISION OF ELI LILLY AND
   COMPANY, FLOYD BAJJALY, M.D,
11 
                    DEFENDANTS.
12 _____________________________________________
   
13                 * * * * * * * * * *
   
14 SUPREME COURT OF TEH STATE OF NEW YORK
   COUNTY OF ORANGE
15 --------------------------------------X
   BRUCE R. MALEN AS EXECUTOR OF THE     : INDEX NO.
16 ESTATE OF BARBARA E. MALEN, AND OF    : 4119/92
   BRUCE R. MALEN, INDIVIDUALLY,         :
17                                       : HON. PETER
       PLAINTIFF                         : PATSALOS,
18                                       : J.S.C.
               -against-                 :
19                                       :
   ELI LILLY & COMPANY, DISTA PRODUCTS   :
20 COMPANY, A DIVISION OF ELI LILLY &    :
   COMPANY, BARRY SINGER AND UNITED      :
21 HOSPITAL,                             :
                                         :
22     DEFENDANTS.                       :
   --------------------------------------X
23 
                   * * * * * * * * * *

                                                 Page 5

 1 
   ---------------------------------X
 2 VALARIE J. FRIEDMAN AND DAVID    : SUPERIOR COURT
   FRIEDMAN, HER HUSBAND,           : OF NEW JERSEY
 3                                  : LAW DIVISION:
           PLAINTIFF,               : MIDDLESEX COUNTY
 4                                  : DOCKET NO.
                                    : L-3191-91
 5 VS.                              :
                                    :
 6 ELI LILLY & COMPANY; DISTA       :
   PRODUCTS INC, A DIVISION OF      :
 7 ELI LILLY & COMPANY; LISS        :
   PHARMACY; MADISON PHARMACY AND   :
 8 JOHN DOES NOS. 1-25 (UNKNOWN     :
   ENTITIES),                       :
 9                                  :
           DEFENDANTS.              :
10 ---------------------------------X
   
11                 * * * * * * * * * *
   
12 SUPREME COURT OF THE STAET OF NEW YORK
   COUNTY OF SUFFOLK
13 -------------------------------------x
   
14 RHOMDA L. HALA and JOSEPH L. HALA,   :
   
15                 Plaintiffs,          : Index No.
                                          14869/90
16  - against -                         :
   
17 ELI LILLY & COMPANY and DISTA        :
   PRODUCTS COMPANY, a DIVISION OF
18 ELI LILLY & COMPANY                  :
   
19                 Defendants.          :
   -------------------------------------x
20 
   
21                 * * * * * * * * * *

                                                 Page 6

 1 
      IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS
 2           COUNTY DEPARTMENT, LAW DIVISION
   
 3 PATRICIA BRACH,                    )
                                      )
 4                  Plaintiff         )
                                      )
 5       v.                           )No. 92 L 13369
                                      )
 6 ELI LILLY AND COMPANY, a foreign   )
   corporation; ALAN N. MILLER, M.D., )
 7 WILLIAM BRUINSMA, Psy.D., and      )
   CONDELL MEMORIAL HOSPITAL,         )
 8                                    )
                    Defendants.       )
 9 
                   * * * * * * * * * *
10 
      IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS
11          COUNTY DEPARTMENT - LAW DIVISION
   
12 RENATO DI SILVESTRO, Individually  )
   and as Special Administrator of    )
13 the Estate of JOHN DI SILVESTRO,   )
   Deceased,                          )
14                                    )
                    Plaintiff,        )
15                                    )
        v.                            ) No. 91 L 7881
16                                    )
   ROBERT L. NELSON, et al.,          )
17                                    )
                    Defendants,       )
18                                    )
   GEORGE MELNICK, M.D. and PETER     )
19 FINK, M.D.                         )
                                      )
20           Respondents in Discovery.)
   
21                 * * * * * * * * * *

                                                 Page 7

 1 
      IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS
 2           COUNTY DEPARTMENT, LAW DIVISION
   
 3 JOAN M. GRYER,                     )
                                      )
 4                    Plaintiff,      )
                                      )
 5      v.                            ) No. 92 L 7387
                                      )
 6 ELI LILLY AND COMPANY, et al.,     )
                                      )
 7                   Defendants.      )
   
 8 
                   * * * * * * * * * *
 9 
      IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS
10           COUNTY DEPARTMENT, LAW DIVISION
   
11 JENNIFER HAMMERLI, as Plenary      )
   Guardian of the Estate of RAY B.   )
12 HAMMERLI, a disabled person,       )
                                      )
13                    Plaintiff,      )
                                      )
14      v.                            ) No. 92 L 2365
                                      )
15 ELI LILLY AND COMPANY, THE         )
   UPJOHN COMPANY, DICKIE KAY, M.D.,  )
16 (former Respondent in Discovery),  )
   and RICHARD CZECHOWICZ (former     )
17 Respondent in Discovery),          )
                                      )
18                    Defendants.     )
   
19                 * * * * * * * * * *

                                                 Page 8

 1 
   IN THE CIRCUIT COURT OF THE SIXTH JUDICIAL CIRCUIT
 2             CHAMPAIGN COUNTY, ILLINOIS
   
 3 LINDA GARDNER, Individually and    )
   as Special Administrator of        )
 4 the Estate of SHANE GARDNER,       )
   deceased,                          )
 5                                    )
                       Plaintiff,     )
 6                                    )
        v.                            ) No. 91 L 1066
 7                                    )
   ELI LILLY AND COMPANY, a foreign   )
 8 corporation,                       )
                                      )
 9                     Defendant.     )
   
10 
                   * * * * * * * * * *
11 
        IN THE NINETEENTH JUDICIAL CIRCUIT COURT
12                LAKE COUNTY, ILLINOIS
   
13 JAMES E. SHEPPARD, Special         )
   Administrator of the Estate of     )
14 KENNETH K. SHEPPARD, Deceased,     )
                                      )
15                    Plaintiff       )
                                      )
16      v.                            ) No. 93 L 124
                                      )
17 GOOD SHEPHERD HOSPITAL, a          )
   corporation, DR. STEWART SEGAL,    )
18 DR. SANFORD SHERMAN, DR. BRUCE     )
   CARLSON, DR. R. BERGLUND, and ELI  )
19 LILLY & COMPANY, a corporation,    )
                                      )
20                    Defendants.     )
   
21                 * * * * * * * * * *

                                                 Page 9

 1 
        SUPERIOR COURT OF THE STATE OF CALIFORNIA
 2 
              FOR THE COUNTY OF LOS ANGELES
 3 
   DR. MARIUS SAINES, etc., et al.,    ) Case No:
 4                                     ) SC 008331
                       Plaintiffs,     )
 5                                     )
        vs.                            )
 6                                     )
   ELI LILLY & COMPANY, a corporation; )
 7 DISTA PRODUCTS COMPANY, a division  )
   of Eli Lilly & Company; and DOBS 1- )
 8 100, inclusive,                     )
                                       )
 9                     Defendants.     )
   ____________________________________)
10 
   
11                 * * * * * * * * * *

                                                 Page 10

 1       THE DEPOSITION OF JAMES G.  KOTSANOS, TAKEN
 2  AT THE OFFICE OF BAKER & DANIELS, 300 NORTH
 3  MERIDIAN STREET, SUITE 2700, INDIANAPOLIS,
 4  INDIANA 46204, ON AUGUST 16, 1993; SAID
 5  DEPOSITION TAKEN PURSUANT TO NOTICE IN ACCORDANCE
 6  WITH THE RULES OF CIVIL PROCEDURE.
 7                 * * * * * * * * * *
 8                A P P E A R A N C E S
 9 
   
10      NANCY ZETTLER
        COUNSEL FOR GROUP A PLAINTIFFS
11      LEONARD M. RING AND ASSOCIATES, P.C.
        111 WEST WASHINGTON AVENUE, SUITE 1333
12      CHICAGO, ILLINOIS  60602
   
13      LAWRENCE J. MYERS
        COUNSEL FOR ELI LILLY AND COMPANY
14      FREEMAN & HAWKINS
        4000 ONE PEACHTREE CENTER
15      303 PEACHTREE STREET, N.E.
        ATLANTA, GEORGIA  30308-3243
16 
        MARGARET M. HUFF
17      ELI LILLY AND COMPANY
        LILLY CORPORATE CENTER
18      INDIANAPOLIS, INDIANA  46285
   
19      MICHAEL D. KRAUSE
        COUNSEL FOR GOOD SHEPHERD HOSPITAL
20      415 WASHINGTON STREET, SUITE 214
        WAUKEGAN, ILLINOIS
21 
        MIGUEL A. RUIZ
22      COUNSEL FOR DEFENDANTS CZECHOWICZ, FINK, BRUINSMA
        CLAUSEN MILLER GORMAN CAFFREY & WITOUS
23      10 SOUTH LASALLE
        CHICAGO, ILLINOIS  60603

                                                 Page 11

 1      PAUL J. CLEMENTI
        COUNSEL FOR DR. DICKIE KAY
 2      HINSHAW & CULBERTSON
        222 NORTH LA SALLE STREET, SUITE 300
 3      CHICAGO, ILLINOIS  60601-1081
   
 4      KATHERINE L. LAWS
        COUNSEL FOR DRS. WITSCHY AND KANNEGANTI
 5      BAILEY AND WILLIAMS
        3500 NCNB PLAZA
 6      901 MAIN STREET
        DALLAS, TEXAS  75202-3714
 7 
        DOUGLAS C. BALLANTINE
 8      COUNSEL FOR DR. LEE COLEMAN
        OGDEN NEWELL & WELCH
 9      1200 ONE RIVERFRONT PLAZA
        LOUISVILLE, KENTUCKY  40202
10 
        PAUL SMITH
11      COUNSEL FOR PLAINTIFFS
        745 CAMPBELL CENTER 2
12      8115 NORTH CENTRAL EXPRESSWAY
        DALLAS, TEXAS  75206

                                                 Page 12

 1                      I N D E X
 2 
 3 DEPOSITION OF JAMES G. KOTSANOS
 4 
 5      DIRECT EXAMINATION BY MS. ZETTLER         14
 6      CROSS EXAMINATIONBY MR. SMITH            200
 7 
 8 
 9      CERTIFICATE                              316
10 
11      ERRATA                                   317
12 
13                      EXHIBITS
14 
15     PLAINTIFFS' EXHIBIT NO. 1                 138
16     PLAINTIFFS' EXHIBIT NO. 2                 172
17     PLAINTIFFS' EXHIBIT NO. 3                 191
18 
19 
20 
21 

                                                 Page 13

 1            COMES JAMES GEORGE KOTSANOS, CALLED BY
 2  THE PLAINTIFF, AND AFTER FIRST BEING DULY SWORN,
 3  WAS DEPOSED AND TESTIFIED AS FOLLOWS:
 4                 DIRECT EXAMINATION
 5 BY MS. ZETTLER:
 6            Q.      Could you state your full name,
 7  please?
 8            A.      James George Kotsanos.
 9            Q.      M.D. or Ph.D?
10            A.      M.D.
11            MS. ZETTLER:  Let the record reflect
12  that this is a discovery deposition of Dr. James
13  Kotsanos --
14            Q.      Did I pronounce that right?
15            A.      Right.
16            MS. ZETTLER:  -- taken pursuant to a
17  notice and the applicable state and local rules
18  of Kentucky.  Dr. Kotsanos, my name is Nancy
19  Zettler, I represent a number of plaintiffs in
20  the Fentress versus Shea Communications case,
21  that's the case that stems from the shootings by
22  Joseph Wesbecker at the Standard Gravure plant in
23  Louisville.
24            MS. LAWS:  We've been reserving

                                                 Page 14

 1  objections except as to the form of the question
 2  and responsiveness of the answer, and the
 3  objection of one defendant has been applicable to
 4  all defendants.
 5            MR. MYERS:  That's fine with us, and as
 6  stated in earlier depositions, the deposition of
 7  this witness and the other witnesses this month
 8  have been cross-noticed in the MBL proceedings
 9  and some related state court cases.
10            MS. ZETTLER:  And as we've been doing
11  in other depos, I'll renew my objection to the
12  cross-noticing of the deposition.
13            Also, before I forget, I would like to
14  make a quick record that I think everybody is
15  aware that Kathy Nold, the court reporter, is
16  related to Bill Nold, who is one of the lawyers
17  on the Fentress case.  I asked Ed Stopher about
18  it right when we began and he had no problems
19  with it, but I don't think we've ever made up a
20  record.  So you are aware of it, do you have a
21  problem with that?
22            MR. MYERS:  Yes, I'm keenly aware of it
23  and there is presently no objection, I don't
24  anticipate one.

                                                 Page 15

 1            Q.      Dr. Kotsanos, have you ever
 2  given a deposition before?
 3            A.      Yes.
 4            Q.      On how many occasions?
 5            A.      Two occasions.
 6            Q.      Can you tell me what those two
 7  occasions were?
 8            MR. MYERS:  Yes, go ahead.
 9            A.      They were both job related with
10  Eli Lilly and Company.
11            Q.      Were either of them related to
12  Fluoxetine hydrochloride?
13            A.      No.
14            Q.      When was the first time you
15  gave a deposition?
16            A.      Maybe four years ago.
17            Q.      Okay.  Can you tell me what
18  that was in relation to?
19            A.      It was in relation to one of
20  our antimicrobial drugs.
21            Q.      Is that a drug that's currently
22  on the market?
23            A.      Yes.
24            Q.      Can you tell me what the drug

                                                 Page 16

 1  was?
 2            A.      Cefazolin.
 3            Q.      Can you spell that?
 4            A.      C-E-F-A-Z-O-L-I-N.
 5            Q.      Was that litigation similar to
 6  this, where somebody was alleged that they were
 7  injured because of taking the drug and sued
 8  Lilly?
 9            A.      Yes.
10            Q.      How about the second occasion,
11  when did that occur?
12            A.      Maybe three years ago.
13            Q.      Okay.  And was that in regards
14  to a Lilly product?
15            A.      In regards to a Lilly product,
16  yes.
17            Q.      Which product?
18            A.      Penicillin.
19            Q.      Is it true that you're an
20  epidemiologist?
21            A.      I have training in
22  epidemiology.
23            Q.      Did you testify in either one
24  of those depositions as an epidemiologist?

                                                 Page 17

 1            A.      No.
 2            Q.      What capacity did you testify
 3  in those depositions?
 4            A.      I testified as the medical
 5  monitor of those products.
 6            Q.      When you say medical monitor,
 7  is that in relation to clinical trials that were
 8  performed on those products?
 9            A.      No.  They were marketed
10  compounds, and I was the monitor of safety and
11  efficacy data if it were generated for those
12  products.
13            Q.      Did you, at any time, work as
14  medical monitor for Fluoxetine?
15            A.      I worked not in the capacity of
16  a medical monitor, per se, but I have worked on
17  Fluoxetine.
18            Q.      Okay.  Since you've given
19  depositions on a couple of occasions, you
20  understand the ground rules as far as having to
21  speak out loud, and you can't shake your head and
22  say uh-huh, and things of that nature?
23            A.      You want me to verbalize all my
24  responses.

                                                 Page 18

 1            Q.      Right.  Also, if you don't
 2  understand any of my questions, then -- I'm not
 3  an epidemiologist so you probably will ask me to
 4  do this a lot, but just ask me to rephrase it and
 5  I'll try to make my question as understandable as
 6  possible, is that okay?
 7            A.      That's fine.
 8            Q.      If you answer the question,
 9  we're going to assume you understood it as asked.
10            A.      Okay.
11            Q.      If you need a break at any
12  time, just let me know and we'll take a break.
13  We usually take one in the morning and we have a
14  lunch break and we take one in the afternoon, but
15  if you need one at any other time, just let us
16  know, okay?
17            A.      Thanks.
18            Q.      When did you start working for
19  Lilly?
20            A.      I began working for Lilly five
21  years ago.
22            Q.      Can you give me an approximate,
23  like a month and a year?
24            A.      August, 1988.

                                                 Page 19

 1            Q.      Have you worked for Lilly
 2  continuously since that date?
 3            A.      Yes.
 4            Q.      Can you give us an idea what
 5  your educational background is, starting with
 6  after high school?
 7            A.      I have a Bachelor of Science
 8  degree, a Medical Doctor degree and a Master of
 9  Science degree.
10            Q.      Okay.  Where and when did you
11  get your Bachelor's?
12            A.      I received all of my degrees
13  from Ohio State University, the Bachelor's was
14  received in 1980.
15            Q.      And what -- did you have a
16  major?
17            A.      Chemistry.
18            Q.      Did you have any minors?
19            A.      No.
20            Q.      How about your M.D., when did
21  you receive that?
22            A.      1984.
23            Q.      And your Master's?
24            A.      I believe that was 1988.

                                                 Page 20

 1            Q.      And what was your Master's in?
 2            A.      Preventive medicine.
 3            Q.      Are you Board certified?
 4            A.      Yes.
 5            Q.      When did you become Board
 6  certified?
 7            A.      Officially by the Board in
 8  1989.
 9            Q.      In what area or areas?
10            A.      Preventive medicine.
11            Q.      What is preventive medicine?
12            A.      It's a science that
13  incorporates numerous disciplines, including
14  epidemiology, biostatistics, health
15  administration, environmental issues, clinical
16  epidemiology.
17            Q.      Is that an area of medicine
18  that would be practiced in the general public or
19  is that something more along the lines of
20  research?
21            A.      It can be both, it can be both
22  research and clinical.
23            Q.      If you were going to practice
24  on a clinical basis, how would that apply to the

                                                 Page 21

 1  treatment of a patient?
 2            A.      It's not very different from
 3  primary care, the focus is more on prevention.
 4            Q.      What's the difference between
 5  epidemiology and clinical epidemiology?
 6            A.      Epidemiology is a science that
 7  looks at the distribution of diseases and factors
 8  that effect that distribution.  Clinical
 9  epidemiology is the application of scientific
10  knowledge in the approach to patient care,
11  decision-making.
12            MS. ZETTLER:  Could you read that back?
13             (THE COURT REPORTER READ BACK THE
14              REQUESTED TESTIMONY.)
15            Q.      I guess I'm a little confused.
16  Could you explain what you mean by application of
17  scientific knowledge, isn't that done with every
18  area of medicine?
19            A.      Clinical epidemiology is --
20  what is the best way to define it for you.  It's
21  not different than usual approaches that
22  physicians take to patient care, if that's what
23  you're asking.
24            Q.      I guess I'm still a little

                                                 Page 22

 1  confused about the differences between the
 2  epidemiology and the clinical epidemiology then.
 3            A.      The epidemiology is the
 4  science, the clinical part is patient care.
 5            Q.      When you first started at Lilly
 6  in August of '88, what was your position?
 7            A.      I started as an associate
 8  clinical research physician.
 9            Q.      And were you assigned to any
10  particular division or area?
11            A.      Yes.
12            Q.      Which area was that?
13            A.      The division at the time, I
14  believe, was called the chemotherapy division.
15            Q.      How long were you a CRA in the
16  chemotherapy division?
17            MR. MYERS:  He didn't say he was a CRA.
18            A.      I just said associate clinical
19  research physician.
20            Q.      I'm sorry.
21            MR. MYERS:  You must have had CRA on
22  the brain or something.
23            Q.      Yes.  CRP, the initials --
24            A.      Actually, ACRP at the time.

                                                 Page 23

 1            Q.      How long were you an ACRP in
 2  the chemotherapy division?
 3            A.      Two years.
 4            Q.      And during that two-year period
 5  of time, did you work on Fluoxetine at all?
 6            A.      I do not believe so.
 7            Q.      You don't have to tell me the
 8  names of those drugs, but can you give me a
 9  general idea of the types of drugs you worked on
10  when you were an ACRP in chemotherapy?
11            A.      I worked on antibiotics
12  primarily.
13            Q.      Were psychotropic drugs dealt
14  with in the chemotherapy division or was that
15  another division?
16            A.      That was another division.
17            Q.      Which division was that back in
18  '88?
19            A.      I don't recall the name of the
20  division.
21            Q.      When you left the chemotherapy
22  division, where did you go?
23            A.      I believe I remained part of
24  the chemotherapy division regarding my home,

                                                 Page 24

 1  however I worked on different projects outside of
 2  antibiotics.
 3            Q.      Were you still an associate
 4  clinical research physician?
 5            A.      When?
 6            Q.      When -- let's see, I believe
 7  you testified earlier that you were an associate
 8  clinical research physician in the chemotherapy
 9  division for about two years starting in '88.
10  Are we still in --
11            A.      After two years, I became a
12  clinical research physician.
13            Q.      Is that approximately August of
14  '90?
15            A.      Yes.
16            Q.      And you remained -- did you
17  remain in the chemotherapy division?
18            A.      Yes.  I believe I was
19  functionally part of chemotherapy division,
20  however I worked on projects outside of the
21  chemotherapy division.
22            Q.      What projects did you work on?
23            A.      I worked on an insulin project
24  and I worked on, after that time, Fluoxetine

                                                 Page 25

 1  projects.
 2            Q.      When did you begin working on
 3  Fluoxetine projects?
 4            A.      I don't remember the exact
 5  time, I believe it was sometime in 1990.
 6            Q.      Why is it that you technically
 7  stayed in the chemotherapy division but worked on
 8  Fluoxetine, if you know?
 9            A.      I believe there's a lot
10  involved with shifting one's category, the
11  paperwork involved with doing it.
12            Q.      You mean as far as transferring
13  you to another division?
14            A.      Doing it on paper, I suppose,
15  there's probably a lot involved with that, so it
16  didn't seem like a necessary step, I presume.
17            Q.      Are you still technically in
18  the chemotherapy division?
19            A.      No.
20            Q.      Where are you now?
21            A.      I'm in the division of health
22  economics research.
23            Q.      When did you move to that
24  division?

                                                 Page 26

 1            A.      The division was formalized
 2  this year, so technically this year.
 3            Q.      And between 19 -- well, let me
 4  ask it this way:  When did you leave the
 5  chemotherapy division?
 6            A.      Well, that's difficult for me
 7  to answer because after 1990 I worked on projects
 8  in different areas, but I believe for salary
 9  purposes and others, I was always tied into the
10  division of chemotherapy, I believe, until we
11  formalized the division of health economics
12  research, and I'm now part of that division.
13            Q.      Have you worked with Fluoxetine
14  continuously since you began working on it
15  sometime in 1990?
16            A.      Not continuously.
17            Q.      Okay.  Why don't you tell me
18  the first time period that you worked on it, you
19  said sometime in 1990 until when?
20            A.      I believe the primary time I
21  worked on Fluoxetine was from about 1990 through
22  the first three quarters of 1991.  Actually, let
23  me -- I think it was up through the FDA advisory
24  committee meeting on anti-depressants, whenever

                                                 Page 27

 1  that date was.
 2            Q.      In September of 1991?
 3            A.      I believe.  Then I worked on
 4  Fluoxetine again, that I can recall, on more
 5  recent projects in the health economic research
 6  area over the past year, and perhaps even a
 7  little longer than that.  It's hard to recall the
 8  exact times.
 9            Q.      What did you work on between
10  the time you stopped working on Fluoxetine in
11  approximately September of '91 and sometime in
12  late '92?
13            A.      A lot of things.  I was the
14  coordinator of a group called the
15  pharmacoepidemiology group, and I worked on
16  building this group to the current division of
17  health economics research, so I was involved with
18  education and recruitment coordination of
19  European activities, just a lot of activities.
20            Q.      The pharmacoepidemiology group,
21  did they have any responsibilities with regards
22  to Fluoxetine when you were the coordinator?
23            A.      I was the coordinator even
24  before September of '91, so due to my

                                                 Page 28

 1  involvement, yes, the pharmacoepidemiology group
 2  was involved.
 3            Q.      That period of time where you
 4  were not working directly on Fluoxetine -- when
 5  you were not working on Fluoxetine from
 6  approximately September of '91 to late '92, did
 7  the group have any responsibility for Fluoxetine?
 8            A.      Well, there may have been
 9  carry-over work from some of the projects I had
10  been involved in, but I don't recall the exact
11  time period, so there's possibly some carry-over
12  work from former projects that I had worked on.
13  So the answer is yes.
14            Q.      So any responsibility that the
15  group would have had with Fluoxetine would have
16  come from your involvement?
17            A.      Primarily with my involvement.
18  In fact, there were some carry-over projects, I
19  recall that now, so yes.
20            Q.      Carry-over projects?
21            A.      Publications.
22            Q.      These are projects that were
23  ongoing after the advisory committee of September
24  of '91?

                                                 Page 29

 1            A.      Projects that may have been
 2  started before and then completed after, yes.
 3            Q.      Can you give me an example of
 4  some of those projects?
 5            A.      Yes.  One specific example is a
 6  publication of suicide mortality trends since
 7  Fluoxetine introduction, which we published in a
 8  scientific journal.
 9            Q.      What journal?
10            A.      American Journal of Public
11  Health.  It was actually a letter to the editor.
12            Q.      Was that letter sent under your
13  signature?
14            A.      I was the second author.
15            Q.      Who else was listed on the
16  letter?
17            A.      Dan Masica, Charles Beasley and
18  Jan Potvin.
19            Q.      What was the purpose of the
20  letter?
21            A.      It was to describe suicide
22  mortality rates in the United States in relation
23  to Fluoxetine prescriptions in the United States.
24            MR. SMITH:  Where was that published?

                                                 Page 30

 1            MS. ZETTLER:  The American Journal of
 2  Public Health.
 3            MR. SMITH:  The American Journal of
 4  Culture?
 5            MS. ZETTLER:  Public Health.
 6            Q.      Did you and other authors
 7  believe that there was a correlation between the
 8  marketing of Fluoxetine and a decrease in
 9  mortality rates, suicide mortality rates?
10            A.      I'm sorry, could you repeat the
11  last question?
12            Q.      Sure.  Did you and your
13  colleagues, Dr. Masica, Dr. Beasley and Dr.
14  Potvin believe that you could show a correlation
15  between the decrease in suicide mortality rates
16  in the United States and the use of Fluoxetine?
17            A.      The descriptive data showed
18  that the trends went in opposite directions,
19  there was a decrease in suicide mortality and an
20  increase in Fluoxetine prescriptions.
21            Q.      Do you believe that that was
22  directly related to the use of Fluoxetine as
23  opposed to maybe more people seeking treatment
24  for depression?

                                                 Page 31

 1            A.      I believe there are a number of
 2  factors for the decrease, and the findings were
 3  reassuring.
 4            Q.      Reassuring based on an
 5  increased prescription of Fluoxetine or
 6  reassuring that an increase seeking of treatment
 7  by people suffering from depression?
 8            A.      Reassuring that the mortality
 9  rate was decreasing.
10            Q.      Besides an increase in the
11  prescriptions of Fluoxetine, what other factors
12  did you take into consideration in coming to your
13  conclusions that there was a decrease in suicide
14  rates and an increase in Fluoxetine that
15  correlated?
16            A.      There were a lot of activities
17  ongoing in heightening awareness about the
18  disease depression, identifying depressed
19  patients and treating depressed patients in the
20  United States during this time period, activities
21  by the National Institutes of Mental Health, and
22  others, including -- I think that summarized it,
23  I think that's what we said in the article as
24  well.

                                                 Page 32

 1            Q.      The National Institute of
 2  Mental Health, I take it you're familiar with
 3  that organization?
 4            A.      Somewhat.
 5            Q.      Are you familiar with their
 6  depression campaign that they have been running
 7  recently?
 8            A.      I believe that's the one I'm
 9  referring to, what we referenced in the letter.
10            Q.      What time period did you take
11  into consideration in your study on mortality
12  versus Fluoxetine ingestion?
13            A.      I believe we looked at -- I
14  cannot recall if we started it in '86 or '87, but
15  either '86 and '87 through '91 or '92.  Again, I
16  don't recall the specific, I would have to refer
17  back to the letter.
18            Q.      To your knowledge, when did the
19  National Institute of Mental Health begin their
20  depression awareness campaign?
21            A.      Again, I don't recall the
22  specific dates.
23            Q.      Can you give me an idea, a
24  year?

                                                 Page 33

 1            A.      No.
 2            Q.      Was it before 1991?
 3            MR. MYERS:  He said he couldn't give
 4  you a specific date.
 5            MS. ZETTLER:  I have a right to refresh
 6  his recollection.
 7            A.      I'd have to refresh my memory
 8  with that information.
 9            Q.      Do you remember when the letter
10  was published in the American Journal of Public
11  Health?
12            A.      In 1992.
13            Q.      To your knowledge what, if any,
14  involvement in the National Institute of Mental
15  Health depression awareness campaign did Eli
16  Lilly have?
17            A.      I do not know.
18            Q.      Are you aware that they gave
19  educational grants to the National Institute of
20  Mental Health in support of the awareness
21  campaign?
22            A.      I guess I do not know.
23            Q.      Besides the letter published in
24  the American Journal of Public Health, what other

                                                 Page 34

 1  publications have you worked on since September
 2  of '91?
 3            MR. MYERS:  Any publications?
 4            MS. ZETTLER:  Fluoxetine related.
 5            A.      We published an abstract of
 6  bleeding events and Fluoxetine, and these are
 7  publications I was directly involved in.
 8            Q.      Where was that published?
 9            A.      It was the abstract book of the
10  American Federation of Clinical Research, I
11  believe is their name.
12            Q.      What's an abstract book?
13            A.      It's a book where they publish
14  abstracts of studies.
15            Q.      Is that a periodical
16  publication or is it more like a textbook type of
17  thing?
18            A.      Do you mean periodic
19  publication?
20            Q.      Right, is it a periodical?
21            A.      It's a periodical type
22  publication rather than a textbook publication.
23            Q.      How often does it come out?
24            A.      I believe it's quarterly.

                                                 Page 35

 1            Q.      Any other papers that you've
 2  been involved in?
 3            A.      Specifically with Fluoxetine?
 4            Q.      Right.  I'm still in the time
 5  period from September of '91 to the present.
 6            A.      I'm glad you clarified that
 7  because I don't recall if that particular
 8  abstract we just talked about occurred in that
 9  time period or not, I would need to refresh my
10  memory on that.
11            Q.      Okay.  Any specific papers you
12  recall being involved in in any way between
13  September of '91 and the present?
14            A.      No other papers published.
15            Q.      Okay.  How about papers that
16  weren't published or a pending publication?
17            A.      No other papers or pending
18  publication.
19            Q.      How about papers that you
20  worked on but never published?
21            A.      There were a number of reports
22  I worked on, but never published.
23            Q.      When you say report, you mean
24  reports for submission to regulatory agencies?

                                                 Page 36

 1            A.      Yes.
 2            Q.      Let's stick with publications
 3  right now.  Any publications that you worked on
 4  that were not published?
 5            A.      No.
 6            Q.      When I say worked on, I don't
 7  mean as a primary author, I mean in any capacity
 8  whatsoever.
 9            A.      I presume you mean worked on
10  with the intent to be an author, whether it's a
11  first, second, third or forth?
12            Q.      We can start with that, sure.
13            A.      No.
14            Q.      Were there any papers that you
15  worked on peripherally where you did not intend
16  or somebody else did not intend for you to be an
17  author that were published, if we can start with
18  were published?
19            A.      Sure.
20            Q.      Can you give me an idea of some
21  of those?
22            A.      I'm trying to recall.  I had
23  some involvement in the suicide meta-analysis
24  paper that was published in the British Medical

                                                 Page 37

 1  Journal in September, '91.
 2            Q.      That was -- the primary author
 3  on that is Dr. Beasley?
 4            A.      Yes.
 5            Q.      Okay.  Any others?
 6            A.      That were published?
 7            Q.      Yes, we'll start with
 8  published.
 9            A.      Not that I can recall.
10            Q.      Do you know if that
11  meta-analysis article that Dr. Beasley published
12  in the British Journal, did that cover just
13  suicidality or did that cover violence aggression
14  also?
15            A.      The British Medical Journal
16  article --
17            Q.      Right.
18            A.      -- focused on suicidality.
19            Q.      To your knowledge did Dr.
20  Beasley or anybody else on behalf of Eli Lilly
21  publish an article that studied the incidence of
22  violent aggressive behavior on people on
23  Fluoxetine?
24            A.      Not that I'm aware of.

                                                 Page 38

 1            Q.      To your knowledge were any such
 2  articles considered for publication or rejected?
 3            A.      Could you repeat your question,
 4  please?
 5            Q.      To your knowledge, was there
 6  ever an occasion where an article that studied
 7  the incidence of violent aggressive behavior with
 8  people on Fluoxetine ever considered, was a
 9  concept of doing an article like that ever
10  considered by somebody at Lilly?
11            A.      I believe that was considered.
12            Q.      Do you know if that was ever
13  implemented?  In other words, did somebody seek
14  to actually publish a paper regarding the
15  incidence of violent aggressive behavior on
16  Fluoxetine?
17            A.      I do not know to what level of
18  effort anyone at Lilly pursued that project.
19            Q.      Okay.  To your knowledge who
20  considered writing a paper on that subject,
21  aggressive violent behavior?
22            A.      The research physician who was
23  working on that was John Heiligenstein.
24            Q.      Do you know if he actually

                                                 Page 39

 1  began work on such an article?
 2            A.      I do not know if he began work
 3  on such an article for publication.
 4            Q.      Was there ever an in-house
 5  study done on the relationship between violent
 6  aggressive behavior and the use of Fluoxetine?
 7            A.      I believe data in that category
 8  of hostility, violence, were evaluated.
 9            Q.      Were you involved in the
10  evaluation of that data?
11            A.      No.
12            Q.      Were you involved in the
13  gathering of that data?
14            A.      No.
15            Q.      How is it that you were aware
16  that Dr. Heiligenstein at least at some point
17  considered studying the incidence of violent
18  aggressive behavior and the use of Fluoxetine?
19            A.      I was involved in the review of
20  his report that he wrote, and aware of his
21  evolving thoughts.
22            Q.      I'm sorry, his evolving
23  thoughts?
24            A.      Evolving thoughts at the time,

                                                 Page 40

 1  yes.
 2            Q.      When you say a review of Dr.
 3  Heiligenstein's report, what report is that?
 4            A.      It's a report that I believe
 5  was submitted to the FDA.
 6            Q.      Was that submitted as a
 7  separate report or was that submitted as part of
 8  the safety update?
 9            MR. MYERS:  When you say the safety
10  update --
11            MS. ZETTLER:  A, I'm sorry.
12            A.      I believe it was just part of a
13  safety update.
14            Q.      And at some point in time, Dr.
15  Heiligenstein or somebody at Lilly considered
16  publishing his report as a paper in a medical
17  journal?
18            A.      Again, like I said earlier, I
19  believe so.
20            Q.      Do you know why it was that
21  that report was never published?
22            A.      I do not know, I was not
23  involved in those discussions.
24            Q.      Who would have been involved in

                                                 Page 41

 1  those discussions?
 2            A.      Certainly John.
 3            Q.      Okay.  Anybody else?
 4            A.      Not that I'm aware of.
 5            Q.      To your knowledge is there a
 6  division or department at Lilly that would review
 7  potential articles for publication in journals?
 8            A.      What do you mean by division?
 9            Q.      Or a committee, or -- I'm just
10  trying to find out if there's some entity within
11  Lilly that would look at a prospective article
12  such as Dr. Heiligenstein's and make decisions on
13  whether or not the subject matter should be
14  pursued, for instance?
15            A.      Certainly if one writes an
16  article, they distribute copies for people to be
17  aware of and to see it and so to sign off on
18  articles before they're submitted for
19  publication.
20            Q.      Is there a regular group of
21  people that would look at such articles?
22            A.      Clearly your own line
23  management would look at the article.
24            Q.      Okay.  What do you mean when

                                                 Page 42

 1  you say your own line management, people up the
 2  ladder from you?
 3            A.      Certainly one's own boss would
 4  review the manuscript.
 5            Q.      Who would be Dr.
 6  Heiligenstein's boss?
 7            A.      At that time?
 8            Q.      Right.
 9            A.      I believe his boss was Dan
10  Masica.
11            Q.      Would Dr. Beasley have to sign
12  off on a report such as Dr. Heiligenstein's
13  violent aggressive behavior report?
14            A.      I don't think so.
15            Q.      How about Robert Zerbe?
16            MR. MYERS:  Before he answers, you're
17  talking about a report and a minute ago --
18            MS. ZETTLER:  I'm sorry, a publication.
19            MR. MYERS:  I think report meant some
20  kind of a regulatory body.
21            A.      So you mean manuscript?
22            Q.      Right.
23            A.      For publication?
24            Q.      Right.

                                                 Page 43

 1            A.      I do not recall now if someone
 2  at Zerbe's level would have signed off on that
 3  report, perhaps, but I do not know for sure.
 4            Q.      Is Dr. Beasley and Dr. Masica
 5  on the same level?
 6            A.      I'm sorry, who?
 7            Q.      Dr. Beasley and Dr. Masica.
 8            A.      At that time?
 9            Q.      Right.
10            A.      No.  At that time Dan Masica
11  was a division director and Dr. Beasley was not a
12  division director.
13            Q.      What was Dr. Beasley at that
14  time?
15            A.      I do not know his official
16  title.
17            Q.      Why would you have reviewed Dr.
18  Heiligenstein's violent aggressive behavior
19  report?
20            A.      Internal methodological peer
21  review.
22            Q.      Okay.  What do you mean by
23  internal methodological peer review?
24            A.      It's not unlike scientific

                                                 Page 44

 1  journals receiving manuscripts and sending them
 2  to outside scientists to review a paper for its
 3  methods, results.
 4            Q.      So what perspective within that
 5  internal methodological peer review process would
 6  be looking at the paper?  In other words, were
 7  you looking at it from an epidemiological
 8  perspective, a statistical perspective, what kind
 9  of perspective?
10            A.      Primarily an epidemiological.
11            Q.      Were you asked to give an
12  opinion as to whether or not a manuscript based
13  on Dr. Heiligenstein's report would be published
14  or submitted for publication?
15            A.      I do not think so.
16            MS. ZETTLER:  Can we take a quick
17  break?
18            MR. MYERS:  Sure.
19             (A SHORT RECESS WAS TAKEN.)
20            Q.      I think before we took a break,
21  you testified that you looked at Dr.
22  Heiligenstein's violent aggressive behavior
23  report from an epidemiological perspective;
24  correct?

                                                 Page 45

 1            A.      Yes.  Could I mention
 2  something?
 3            Q.      Sure.
 4            A.      During the break I thought
 5  about one of the answer I had given you
 6  previously.  I was not always part of the
 7  chemotherapy division before becoming part of the
 8  division of health economics research, I recall
 9  they did undertake the paperwork to make us part
10  of the division of neuropharmacology and
11  pharmacoepidemiology, so there was an
12  intermediary step there, just so you know.
13            Q.      So between the chemotherapy
14  division and the new division that was created
15  this year --
16            A.      Yes, we were part of the
17  division of neuropharmacology and
18  pharmacoepidemiology.
19            Q.      Okay.  And Fluoxetine fell
20  under, I believe, one of those two divisions of
21  that larger division of pharmacology and
22  neuropharmacology?
23            A.      I guess I don't know what you
24  mean by Fluoxetine fell under it.

                                                 Page 46

 1            Q.      Was that one division,
 2  neuropharmacology, and was it
 3  neuropsychopharmacology and psychopharmacology?
 4            A.      No, I said division of
 5  neuropharmacology and pharmacoepidemiology.
 6            Q.      Okay.  Is that division still
 7  in existence, neuropharmacology and
 8  pharmacoepidemiology division?
 9            A.      In a revised format.  Since the
10  pharmacoepidemiology part is no longer part of
11  it, I believe they shortened their name.
12            Q.      So now it's just the
13  neuropharmacology division?
14            A.      Well, I don't know if they use
15  that name.
16            Q.      Okay.  And the
17  pharmacoepidemiology division or a portion of
18  that division is now under the, what do you call
19  it, the -- I'm sorry, what's the division you're
20  working with now?
21            A.      Division of health economics
22  researchs.
23            Q.      And the pharmacoepidemiology
24  portion of the division is now under that?

                                                 Page 47

 1            A.      Well, we became the division of
 2  health economics research, we changed our name.
 3            Q.      Before we go on to the
 4  epidemiological perspective of Dr.
 5  Heiligenstein's study, could you give me an idea
 6  of what your responsibilities were as an
 7  assistant clinical research physician when you
 8  first started with Lilly in '88?
 9            A.      I was the medical monitor of a
10  clinical trial of an oral antibiotic and also
11  responsible for monitoring several marketed
12  antibiotic products.
13            Q.      What does a medical monitor do,
14  that's different than a clinical investigator;
15  correct?
16            A.      I don't know where the word
17  clinical investigator came from, but to help you
18  with a medical monitor definition, the medical
19  monitor is responsible for safety and efficacy of
20  the products assigned to them, whether they be
21  investigational products or marketed products.
22            Q.      Okay.  What do you mean when
23  you say they're responsible for safety and
24  efficacy of the product?

                                                 Page 48

 1            A.      Evaluation the safety data and
 2  efficacy data, evaluating published reports on
 3  safety or efficacy data, those types of
 4  activities.  I'm not even sure if the word
 5  medical monitor is formally defined at Lilly, but
 6  I use it.
 7            Q.      Did you have any
 8  responsibility, direct responsibility, over
 9  clinical trials of any of those drugs?
10            A.      I mentioned one, the oral
11  antibiotic, and that was at that time.
12            Q.      Did you actually run the
13  clinical trial yourself or did you oversee the
14  running of the clinical trial?  In other words --
15  well, let me ask you this:  Was that trial on
16  site or off site, was that at Lilly or off site?
17            A.      I guess I'm having a hard time
18  answering your question because I'm not sure what
19  you want to know.
20            Q.      I guess what was your
21  involvement in the clinical trial on the
22  antibiotic that we talked about earlier?
23            A.      I made sure that the
24  investigators participating in the trial followed

                                                 Page 49

 1  the protocol, I answered their questions about
 2  it, I answered questions from a medical
 3  standpoint, I was involved in evaluating the
 4  safety and efficacy data associated with that
 5  trial.
 6            Q.      And the clinical investigators
 7  that you worked with, were those people who were
 8  employed directly by Lilly or were they working
 9  like on a grant or contract basis outside of
10  Lilly?
11            A.      They were not direct employees
12  of Lilly, we worked with them on a grant basis.
13            Q.      And when you originally became
14  involved with Fluoxetine, what were your
15  responsibilities?
16            A.      I was primarily involved in
17  applying epidemiological methods and approaches
18  in the analysis of selected safety projects.
19            Q.      And I believe you testified
20  earlier that you became involved with Fluoxetine
21  sometime in 1990?
22            A.      As I said, thereabouts, because
23  I cannot recall the exact time.
24            Q.      It was prior to the FDA

                                                 Page 50

 1  advisory committee meeting in September of '91,
 2  though?
 3            A.      Yes.
 4            Q.      Did the work that you did on
 5  Fluoxetine prior to September of '91 relate in
 6  any way to preparation for that advisory
 7  committee meeting?
 8            A.      Yes.
 9            Q.      Can you give me an idea of what
10  some of your responsibilities regarding
11  preparation for the advisory committee meeting
12  were?
13            A.      I was involved in preparing
14  back-up materials in the event questions were
15  raised at the advisory committee meeting about
16  topics directly or indirectly related to the
17  focus of the advisory committee meeting.
18            Q.      And the focus of the advisory
19  committee meeting was suicidality and the use of
20  Fluoxetine?
21            A.      Correct, I believe that's
22  right.
23            Q.      Did they have a focus at all on
24  violent aggressive behavior and the use of

                                                 Page 51

 1  Fluoxetine at that meeting?
 2            MR. MYERS:  They?
 3            MS. ZETTLER:  The FDA.
 4            MR. MYERS:  Thank you.
 5            A.      I do not recall what the
 6  initial announcement said, I do not believe so,
 7  but I do not recall specificly what was
 8  specifically said in the announcement.
 9            Q.      Would you agree that to a
10  certain extent the subject matters relate, and
11  when I say subject matters, I mean suicidality
12  and violent aggressive behavior?
13            MR. MYERS:  Let me object to the form
14  in that I think it's overly broad.  When you say
15  relate, what do you mean?
16            MS. ZETTLER:  That they interrelate,
17  that there are elements of violent aggressive
18  behavior in suicidality.
19            A.      That's a complex question, I
20  don't know if I can answer that.
21            Q.      Why is it complex?
22            A.      There are many elements to the
23  disease depression, many components of it.  The
24  relation of any one component to another within

                                                 Page 52

 1  depression is hard to answer with a simple yes or
 2  no response.
 3            Q.      So in other words, given the
 4  complexity of the disease process of depression,
 5  it's difficult to relate certain behaviors
 6  directly to the disease?
 7            A.      No, that --
 8            MR. MYERS:  Before he answers, let me
 9  object to the form, I think he said it was
10  difficult to answer your question is what he
11  said.
12            A.      I was going to say no, that's
13  not what I said.
14            Q.      I guess I don't understand what
15  you mean by it's difficult, given the disease
16  process it's difficult to answer the question, I
17  guess I don't understand that.
18            A.      Can you repeat your initial
19  question again?
20            Q.      We'll have her read it back.
21             (THE COURT REPORTER READ BACK THE
22              REQUESTED TESTIMONY.)
23            Q.      The original question was
24  whether or not there was a relationship between

                                                 Page 53

 1  suicidality and violent aggressive behavior.
 2            A.      Right.
 3            Q.      I don't understand why the
 4  question is complex.
 5            A.      Well, I asked if you could
 6  repeat the initial question again because I think
 7  that's --
 8            Q.      Would you agree that to a
 9  certain extent violent aggressive behavior
10  relates to suicidality?  In other words, there's
11  a violent aggressive component to suicidality?
12            MR. MYERS:  Same objection as to the
13  form.  Go ahead and answer it if you can.
14            A.      Again, I find this area complex
15  and I don't believe I can give you an answer to
16  your question.
17            Q.      In Dr. Heiligenstein's violent
18  aggressive behavior report, he said you were
19  looking at it from an epidemiological
20  perspective.  Can you tell us what that entailed?
21            A.      I do not recall specifically
22  what elements I reviewed at the paper because
23  it's been quite a while ago.
24            Q.      Can you tell me generally?

                                                 Page 54

 1            A.      In general, if I review a
 2  manuscript I focus on the methodological approach
 3  used.  In other words, were the study objectives
 4  clearly defined, was a study population clearly
 5  defined and chosen, those sorts of issues.
 6            Q.      Did you find that in the case
 7  of Dr. Heiligenstein's report that the objectives
 8  were clearly defined?
 9            A.      I do not remember.
10            Q.      Do you recall what the
11  objectives were?
12            A.      No, I could not tell you what
13  they were specifically.
14            Q.      How about the patient
15  population, did you find that patient population
16  in Dr. Heiligenstein's violent aggressive
17  behavior report were clearly defined?
18            A.      Again, I would need to review
19  the paper in order to answer your questions --
20  or, I'm sorry, the report.
21            Q.      Do you recall what the patient
22  population was in that report?
23            A.      Again, I do not recall what the
24  specific patient population was in that report.

                                                 Page 55

 1            Q.      Obviously it was at least
 2  patients on Fluoxetine; correct?
 3            A.      Yes.
 4            Q.      Within that general category,
 5  do you recall, like, for instance what diseases
 6  they were being treated for?
 7            A.      No.
 8            Q.      Was it -- was depression
 9  involved, do you know?
10            A.      Again, I don't recall.
11            Q.      Did you attend any meetings at
12  which Dr. Heiligenstein's violent aggressive
13  behavior report was discussed?
14            A.      What type of meetings?
15            Q.      Any type of meetings.
16            A.      Depending on how you define
17  meetings.  We certainly had periodic internal
18  meetings to update each other on the work we're
19  doing, so yes.
20            Q.      Would you have departmental
21  meetings on a regular basis?
22            A.      There were internal meetings
23  scheduled.
24            Q.      Who would participate in these

                                                 Page 56

 1  meetings from different divisions, can you give
 2  me an idea of who the representatives were from
 3  the different divisions, if any?
 4            A.      The ones I recall most vividly,
 5  obviously, are those that are working on the
 6  different projects.  For example, John would be
 7  there and I would be there and the division
 8  director.  But outside of that, I cannot recall
 9  specifically who else was there.
10            Q.      And the division director at
11  the time that Dr. Heiligenstein was working on
12  this report was Dan Masica, right?
13            A.      Yes.
14            Q.      Do you recall having a meeting
15  with Dr. Heiligenstein and Dan Masica regarding
16  Dr. Heiligenstein's violent aggressive behavior
17  report?
18            A.      Can you clarify your question,
19  please?
20            Q.      Sure.  Do you specifically
21  remember attending a meeting -- start it this
22  way:  Do you specifically remember attending any
23  meeting where the subject matter was Dr.
24  Heiligenstein's violent aggressive behavior

                                                 Page 57

 1  report?
 2            A.      I think the only way I can
 3  answer your question is to say in routine
 4  meetings we would go over the different work
 5  everyone was doing, so, yes, I recall attending a
 6  meeting where this project was discussed, so --
 7            Q.      Okay.
 8            A.      -- yes.
 9            Q.      And besides Dr. Heiligenstein
10  and -- is Dan Masica an M.D.?
11            A.      Yes.
12            Q.      Dr. Masica and Dr.
13  Heiligenstein, do you recall anybody else being
14  present at that meeting or those meetings?
15            A.      There were nonphysicians in
16  attendance at the meetings on occasion, yes, but
17  I cannot recall specifically who these
18  individuals were.
19            Q.      Would these be like chemical
20  research associates or people of that nature?
21            A.      On occasion, yes.
22            Q.      Anybody else that would have
23  been possibly attending these meetings?
24            A.      People that had anything to do

                                                 Page 58

 1  with the projects would be present at the
 2  meetings.
 3            Q.      Do you ever recall any
 4  representative from the marketing department
 5  being at any of the meetings discussed in Dr.
 6  Heiligenstein's report?
 7            A.      Could you be more specific,
 8  please?
 9            Q.      Sure.  Would a marketing
10  representative be present at any of these
11  internal meetings, generally?
12            MR. MYERS:  Any meetings?
13            MS. ZETTLER:  Any meetings, generally.
14            A.      Well, at any meeting, the
15  answer is yes.
16            Q.      Would a marketing
17  representative be involved in a meeting
18  discussing a report such as Dr. Heiligenstein's
19  violent aggressive behavior report, not
20  specifically Dr. Heiligenstein's but something of
21  that nature?
22            A.      Could you repeat your question
23  one more time?
24            Q.      Let me ask it this way:  Dr.

                                                 Page 59

 1  Heiligenstein's violent aggressive behavior
 2  report was a post-marketing report; correct, it
 3  was done after approval of the use of Prozac for
 4  depression was given by the FDA, right?
 5            A.      If that is your definition of a
 6  post-marketing report, then yes, it was compiled
 7  after marketing of Prozac.
 8            Q.      To your knowledge did the
 9  marketing department at Lilly, and when I say the
10  marketing department I mean either
11  representatives of Dista or any arm of marketing
12  that may or may not be within Lilly itself, were
13  any of those types of people involved in any way
14  with either reporting or preparing of Dr.
15  Heiligenstein's violent aggressive behavior
16  report?
17            A.      I do not recall or know if any
18  marketing representives had any input or comment
19  on the specific project, but in general,
20  scientists would write the scientific reports at
21  Lilly.
22            Q.      Would the marketing department
23  have any input as to whether or not a certain
24  manuscript would be submitted for publication?

                                                 Page 60

 1            A.      They were never part of any
 2  sign-off or formal review that I'm aware of.
 3            Q.      Okay.  How about informally?
 4            A.      Even from an informal
 5  perspective, a scientific report was prepared and
 6  reviewed and commented on from the scientific
 7  perspective.
 8            Q.      So the answer is no?
 9            A.      I guess the way you worded your
10  question, the answer would be no, but clearly
11  reports would be shared internally,
12  cross-functionally, and not just limited to a
13  medical science side.
14            Q.      Okay.  Other than Dr. Beasley's
15  meta-analysis article and Dr. Heiligenstein's
16  violent aggressive behavior report, do you recall
17  working indirectly on any other manuscripts
18  published by Lilly with regards to Fluoxetine?
19            MR. MYERS:  Let me just object to the
20  form because you are now -- one was a report, one
21  was an article which was a manuscript at one
22  time.
23            MS. ZETTLER:  Well, we're still
24  limiting it to the manuscripts.

                                                 Page 61

 1            A.      Could you repeat it one more
 2  time?
 3            Q.      Sure.  Other than Dr.
 4  Heiligenstein's -- well, Dr. Heiligenstein's
 5  violent aggressive behavior report, which was
 6  never published; correct, as a manuscript?
 7            A.      Again, not that I'm aware of.
 8            Q.      But Dr. Beasley's suicide
 9  meta-analysis article was published; correct?
10            A.      Yes.
11            Q.      Right now I'm limiting my
12  questions to any manuscripts that you may or may
13  not have worked on, okay, not reports for
14  submission to regulatory agencies, but just any
15  manuscripts that you may have worked on that were
16  either published or to be published.
17            MR. MYERS:  Regarding Fluoxetine?
18            A.      I believe -- I guess I'm not
19  sure what you're specifically --
20            Q.      I don't want to confuse right
21  now a manuscript with a report for submission,
22  you know, like reports to the FDA.  Right now I
23  just want to focus on manuscripts.  I believe,
24  really, your definition of a manuscript was

                                                 Page 62

 1  something that would be submitted for
 2  publication?
 3            A.      Yes.
 4            Q.      That's what I want to focus on
 5  right now.
 6            A.      Papers that were submitted for
 7  publication.
 8            Q.      Right, is my category, as
 9  opposed to any reports that would have been
10  submitted to any regulatory agencies.
11            A.      Okay.
12            Q.      Okay?  Other than Dr. Beasley's
13  article, do you recall working directly or
14  indirectly on any other manuscripts that were to
15  be published regarding Fluoxetine?
16            MR. MYERS:  What time period?
17            Q.      Any time period throughout your
18  entire career working on Fluoxetine.
19            A.      I do not recall working on any
20  other reports that ultimately were submitted for
21  manuscripts for publication.  I could have, but I
22  do not remember.
23            Q.      Other than reports that were
24  eventually submitted for publication, did you

                                                 Page 63

 1  work on any manuscripts related to Fluoxetine?
 2  Earlier you testified that there was a letter
 3  that was published by Dr. Beasley and you and Jan
 4  Potvin, and I believe Dan Masica.  Did you work
 5  on any other articles, letters, things of that
 6  nature, that were either meant to be published or
 7  were actually published regarding Fluoxetine?
 8            A.      I do not recall.  I could have,
 9  but I do not recall ones where I was not an
10  author.
11            Q.      Any others besides the ones we
12  talked about already where you were an author?
13            A.      I believe I told you all of the
14  ones I worked on which were published.
15            Q.      Okay.  And that would be the
16  letter that we just talked about and Dr.
17  Beasley's article in the Brittish Medical
18  Journal?
19            MR. MYERS:  He wasn't an author on
20  that.
21            A.      I was not an author on Dr.
22  Beasley's manuscript in the British Medical
23  Journal.
24            Q.      I don't think we got past the

                                                 Page 64

 1  letter that was published in the American Journal
 2  of Toxicology.
 3            MR. MYERS:  Public Health.
 4            Q.      Public Health, sorry.
 5            A.      Well, I mentioned the abstract,
 6  I believe it's called the American Federation of
 7  Clinical Research.  I could be wrong about that
 8  title, I would need to review that abstract and
 9  journal, if you want to call it a journal, to
10  make sure that's all, but I believe I mentioned
11  all of them.
12            Q.      So the abstract and the letter
13  were the two that you were listed as an author;
14  correct?
15            A.      To the best of my knowledge,
16  those are the ones where I'm listed as an author,
17  and whether or not I worked on others that
18  ultimately were manuscripts submitted for
19  publication, I do not recall or know.
20            Q.      Okay.  How about we focus now
21  on reports that were submitted to regulatory
22  agencies, okay?  When I say regulatory agencies,
23  I don't mean just the FDA.
24            A.      Okay.

                                                 Page 65

 1            Q.      Besides Dr. Heiligenstein's
 2  violent aggressive behavior report, did you work
 3  on any other reports submitted to regulatory
 4  agencies regarding Fluoxetine?
 5            A.      Yes.
 6            Q.      Can you tell me about those?
 7            A.      What would you like to know
 8  about them?
 9            Q.      Start with subject matter,
10  Fluoxetine as it relates to what?
11            A.      Well, as part of a routine
12  safety review, I worked on just about any safety
13  category in terms of being involved in the
14  preparation of regulatory reports.
15            Q.      How often were regulatory
16  reports submitted to the FDA?
17            MR. MYERS:  Before he answers, let me
18  object to the form only to the extent that I
19  think I understand what you're asking him, but I
20  don't know whether you're asking him pursuant to
21  specific federal regulations, how often did Lilly
22  have to submit certain reports on certain
23  subjects to the FDA or any other regulatory
24  agency.  If that's what you're asking him, that's

                                                 Page 66

 1  certainly overly broad and would call on him to
 2  give you a recitation of what the regs say.
 3            Q.      You didn't start working on
 4  Fluoxetine until 1990; correct, sometime in 1990?
 5            A.      Thereabouts.
 6            Q.      Okay.  Is it your understanding
 7  that Lilly submitted periodic safety updates to
 8  the FDA regarding Fluoxetine?
 9            A.      Yes.
10            Q.      Okay.  And were you involved in
11  the preparation of those safety updates?
12            A.      Some of them.
13            Q.      When you say some of them,
14  would there be a reason that you were involved in
15  some and not involved in others?
16            A.      I suppose it depended on work
17  load distribution.
18            Q.      Okay.  You weren't assigned
19  just specific areas regarding safety, such as
20  suicidality and Fluoxetine as opposed to, say,
21  headaches and Fluoxetine, or something of that
22  nature?
23            A.      Again, I worked on a host of
24  different routine analyses for Fluoxetine, for

                                                 Page 67

 1  different safety categories.
 2            Q.      When you say safety categories,
 3  what do you mean?
 4            A.      Oh, just by categorization of
 5  terms.
 6            Q.      Adverse event terms?
 7            A.      Yes.
 8            Q.      So your assignments would be
 9  broken down as to event terms?
10            A.      To some degree, yes.
11            Q.      Would your responsibilities be
12  broken down by body system?  In other words,
13  would you be responsible for any central nervous
14  system related adverse events?
15            A.      Not necessarily again.
16            Q.      Okay.  Why don't you give me an
17  idea of some of the subject matters within the
18  term of safety that you worked on?
19            A.      I worked on bleeding events.
20            MR. SMITH:  Did you say bleeding
21  events?
22            THE WITNESS:  Yes.
23            A.      Maybe it would help you to just
24  say as part of some of the routine reports that

                                                 Page 68

 1  went in they were broken out by different body or
 2  disease areas, so the bleeding system would be
 3  one, the pulmonary system would be another,
 4  examples such as that.
 5            Q.      Okay.  For example, say, in the
 6  first quarter of 1992, Lilly got a greater number
 7  of reports of, say, tremor, from people on
 8  Fluoxetine.  Would you then be assigned a task to
 9  take a look at tremor as it relates to the use of
10  Fluoxetine from an epidemiological standpoint or
11  is it just a general overview of all adverse
12  events reported on a quarterly basis?
13            A.      As part of routine monitoring,
14  we would look at all of them, and then if there
15  were any trends, or anything in our medical
16  opinion needed to be further evaluated, we would
17  undertake those projects.  But as part of the
18  routine review, we look at all of them.
19            Q.      Would you report on all of
20  them?
21            MR. MYERS:  When you say report --
22            MS. ZETTLER:  Report to the FDA on all
23  of them, adverse events for a previous quarter.
24            A.      Yes, we would report on all of

                                                 Page 69

 1  them.
 2            Q.      Would it be a matter of going
 3  through the report and saying last quarter we
 4  only had ten reports of headaches, this quarter
 5  we have eleven reports of headaches, or is it
 6  more of a report generally that the incidence of
 7  reporting of certain events is about the same
 8  except in these areas, i.e., tremor, headache, or
 9  depending on what was reported for the previous
10  quarter?
11            A.      It was usually more than just a
12  review of the numbers of event, it would involve
13  a medical review of the records of these terms.
14            Q.      I guess what I'm trying to find
15  out is is a particular adverse event looked at
16  from the perspective of an increase in reporting
17  that adverse event, or does the medical review or
18  opinion, as you say, go to every single adverse
19  event that's reported during a quarter?
20            A.      I guess I didn't understand
21  that particular question.
22            Q.      Okay.  I guess what I'm trying
23  to find out, is you guys don't sit there every
24  quarter and say okay, we've got another report of

                                                 Page 70

 1  headache, but the percentage hasn't increased
 2  from last quarter so we're not going to report on
 3  it.
 4            A.      Well --
 5            Q.      I'm trying to understand what
 6  the procedure is.  Is there something that may
 7  alert you to take a closer look at a given
 8  adverse event as opposed to another adverse
 9  event?
10            A.      I cannot quote for you what the
11  regulations require.
12            Q.      Right.
13            A.      But we would do routine reviews
14  of adverse events.  We would pay particular
15  attention to serious adverse events, but we
16  evaluated all adverse events whether they were
17  serious or not.
18            Q.      For what purposes did you
19  evaluate all adverse events?
20            A.      Certainly the annual report to
21  the FDA would require a review of all adverse
22  events, but we would undertake evaluations
23  whenever we felt it was necessary.
24            Q.      Okay.  What do you mean when

                                                 Page 71

 1  you say review, you mean it's just a matter of
 2  saying oh, yes, here's another report of a
 3  headache, or do you go into a more in-depth
 4  analysis of, say, a causal relationship to the
 5  drug?
 6            A.      Adverse event reports always
 7  require medical judgment regardless of the
 8  seriousness of the adverse event, and any
 9  physician reviewing the adverse event reports
10  would certainly review and comment on each one.
11  And I guess I don't know how else to answer your
12  question.
13            Q.      Okay.  When you say medical --
14  any adverse event would require a medical
15  judgment, obviously a number of different
16  judgments can be made about a different adverse
17  event in the perspective of is it causally
18  related to the drug, is the event that's reported
19  by the reporter an accurate description of what
20  occurred or things of that nature, right?
21            A.      A number of factors that need
22  to be evaluated.  You've listed a couple, but
23  there are certainly numerous ones and they
24  usually can pertain to the specific event

                                                 Page 72

 1  depending on what kind of medical condition is
 2  being reported on, how much information is needed
 3  and details are needed to make a better
 4  assessment of it.
 5            Q.      Were you ever asked to review a
 6  given adverse event and render medical judgments
 7  regarding the adverse event?
 8            A.      Yes, I was.
 9            Q.      Give me an idea of what kinds
10  of medical judgments you've been asked to render.
11  It doesn't have to be a specific adverse event,
12  you can give me in general.
13            A.      Again, I cannot quote for you
14  what types of regulations we needed to follow,
15  however for adverse event reports, we would
16  assess its expectancy and relationship to the
17  drug therapy in general.
18            Q.      Okay.  When you say expectancy,
19  do you mean expectancy as it's defined by the FDA
20  or expectancy as an independent medical judgment?
21            A.      As defined by the FDA.
22            Q.      FDA regulations?
23            A.      Uh-huh.
24            Q.      What is your understanding of

                                                 Page 73

 1  what the FDA's definition of expected adverse
 2  event is?
 3            A.      I cannot give you their
 4  verbatim definition.
 5            Q.      I'm asking for your
 6  understanding of what it is.
 7            A.      My understanding is the term
 8  shows up in the package insert for a marketed
 9  compound.
10            Q.      If it's listed in the package
11  insert, it is considered expected; correct?
12            A.      Correct.
13            Q.      And the terms that are listed
14  in the package insert are put there in part by
15  the manufacturer; correct?
16            A.      Of course the package insert is
17  data driven.
18            Q.      By the manufacturer's data?
19            A.      Primarily, but not always.
20            Q.      My original question was that
21  the data listed came in part from the
22  manufacturer?
23            A.      Yes.
24            Q.      Now within that broad

                                                 Page 74

 1  definition of it if it appears in the package
 2  insert, it's considered expected.  Is there any
 3  other limitations, in other words does it have to
 4  be something that is listed as an adverse event
 5  for it to be expected?
 6            A.      Could you repeat that?
 7            Q.      I guess I'm just trying to
 8  narrow it down.  Is it virtually anything that's
 9  listed in the package insert is considered
10  expected or are there some other caveats, does it
11  have to be, for instance, overdose, does an
12  overdose have to be specifically listed in the
13  adverse event section of the package insert for
14  it to be considered?
15            A.      Let me make the following
16  qualification:  I haven't done this in several
17  years so I'm a little bit foggy on exactly how it
18  took place at the time I did it.  I remember
19  doing it -- being able to do it and understanding
20  it at the time, but now, after several years, I'm
21  a little bit hazy and I don't feel comfortable
22  answering that particular question.
23            Q.      Were you asked to make medical
24  judgments as to expectancy in relationship with

                                                 Page 75

 1  the study drug with regards to Fluoxetine?
 2            MR. MYERS:  Let me object to the form
 3  when you say the study drug.
 4            MS. ZETTLER:  Okay, the drug.
 5            A.      Yes.
 6            Q.      And this expectancy criteria
 7  was applied to Fluoxetine as well as other drugs
 8  at Lilly; correct?
 9            A.      Other Lilly drugs, yes.
10            Q.      The expectancy was applied to
11  Fluoxetine also, the definition of expectancy?
12            A.      Maybe I didn't understand what
13  you just said.
14            Q.      I'm just trying to find out --
15  well, let me ask you this:  Did you make these
16  medical judgments with regards to other drugs
17  manufactured by Lilly, besides Fluoxetine?
18            A.      Yes.
19            Q.      So was the same definition of
20  expected event applied to Fluoxetine that was
21  applied to the other drugs?
22            A.      I recall that, I seem to recall
23  that it was, yes.
24            Q.      Did you have an understanding

                                                 Page 76

 1  that there was a definition with regards to the
 2  seriousness of an adverse event?
 3            A.      I know there's a definition for
 4  seriousness of an event based on FDA regulations,
 5  but I cannot tell you at this time what it is
 6  now.
 7            Q.      There are various categories of
 8  events that are considered automatically serious;
 9  correct, such as death, congenital anomalies,
10  hospitalization, things of that nature?
11            A.      Again, there are certain
12  categories that met a seriousness definition,
13  yes.
14            Q.      Do you recall what any of those
15  categories are?
16            A.      I believe you mentioned a
17  couple such as death and hospitalization.
18            Q.      How about overdose, is that
19  considered a serious adverse event?
20            A.      I don't recall now.
21            Q.      Do you have any specific
22  recollection of working on any given quarterly
23  safety reports?
24            A.      Any type of quarterly safety

                                                 Page 77

 1  report or do you mean a regulatory report?
 2            Q.      Let's start with regulatory
 3  reports.
 4            A.      Yes, I worked on regulatory
 5  quarterly reports.
 6            Q.      Do you remember any specific
 7  quarterly report related to Fluoxetine that you
 8  worked on?
 9            A.      I worked on several, so I
10  cannot really address any particular one for you
11  at this point unless there's any you wanted me to
12  address.
13            Q.      Do you recall working on any
14  specific safety issue as reported in a quarterly
15  report, for instance you mentioned earlier that
16  you worked on the issue of bleeding.  Do you
17  recall any other issues that you worked on with
18  regards to Fluoxetine?
19            MR. MYERS:  Is the subject matter
20  quarterly reports now?
21            MS. ZETTLER:  The safety reports, the
22  quarterly safety reports that he worked on a
23  number of them.
24            A.      Again, I worked on a diverse

                                                 Page 78

 1  number of different adverse event terms in the
 2  safety quarterly reports.
 3            Q.      What I'm asking for is an idea
 4  of examples of some of the other -- some examples
 5  of some of the other adverse events that you
 6  worked on?
 7            A.      Well, in the hematological
 8  category, clearly I worked on bleeding events, I
 9  worked on other events within the hematological
10  category, I worked on pulmonary events and
11  different events within the pulmonary category.
12            Q.      Did you work on central nervous
13  system events, that category?
14            A.      I would need to review the
15  reports to see if any of the terms I worked on
16  fell underneath that category in order to answer
17  you.
18            Q.      Did you work on any body as a
19  whole category?
20            A.      It's possible.
21            Q.      Did you work on suicidality?
22            A.      In the quarterly safety
23  reports?
24            Q.      Right.

                                                 Page 79

 1            A.      Typically not.
 2            Q.      Did you work on hostility?
 3            A.      Typically not.
 4            Q.      Who did?
 5            A.      The psychiatrists would work on
 6  those.
 7            Q.      When you say the psychiatrists,
 8  who do you mean, like Dr. Masica?
 9            A.      No.  For example John
10  Heiligenstein or Charles Beasley.
11            Q.      Anybody else?
12            A.      Dr. Wheadon.
13            Q.      That's David Wheadon?
14            A.      Yes.  That's all I can recall
15  right now.
16            Q.      How about Louise Levine?
17            A.      At the time I was working on
18  them, I don't recall her working on them.
19            Q.      How about Dr. Jamie Street?
20            A.      I recall Dr. Street working on
21  them, although I was just listing the
22  psychiatrists for you.
23            Q.      Okay.  And to your knowledge
24  she's not a psychiatrist; correct?

                                                 Page 80

 1            A.      To my knowledge, that's
 2  correct.
 3            Q.      Any other doctors, regardless
 4  of their specialty, that would work on
 5  suicidality quarterly reports?
 6            A.      Only one other I can recall is
 7  Dr. David Goldstein.
 8            Q.      Is Dr. Goldstein still with
 9  Lilly?
10            A.      Dr. David Goldstein is, the one
11  I'm referring to.
12            Q.      Any other Dr. Goldstein that
13  worked on Fluoxetine?
14            A.      Not that I'm aware of.
15            Q.      Any other Dr. Goldsteins that
16  were at Lilly or are at Lilly?
17            A.      I don't know.
18            Q.      I thought you were making a
19  differentiation between David Goldstein and maybe
20  somebody else?
21            MR. MYERS:  Just like Robert Taylor.
22            Q.      Dr. Kotsanos, you said earlier
23  that you were not an epidemiologist; correct?
24            A.      I'm sorry?

                                                 Page 81

 1            Q.      You're not an epidemiologist,
 2  therefore you're not Board certified as an
 3  epidemiologist?
 4            A.      I said I was trained in
 5  epidemiology and I'm Boarded in preventive
 6  medicine.
 7            Q.      And under that category of that
 8  specialty, epidemiology is included?
 9            A.      It's a component of preventive
10  medicine training.
11            Q.      Is there a specialty, can you
12  get Board certified in epidemiology?
13            A.      Not that I'm aware of.
14            Q.      Besides yourself, are there any
15  other epidemiologists on staff at Lilly that
16  worked on Fluoxetine or are working on
17  Fluoxetine?
18            A.      At the time I worked on
19  Fluoxetine, there were no people that worked on
20  it that I'm aware of that claimed they were
21  epidemiologists, however the application of
22  epidemiological science can be done by anyone
23  that has an understanding or has a background in
24  the area.

                                                 Page 82

 1            Q.      Was there anybody at Lilly
 2  while you worked on Fluoxetine that did act as an
 3  epidemiologist with regards to Fluoxetine?
 4            A.      What do you mean by act as an
 5  epidemiologist?
 6            Q.      Were you charged with -- you
 7  said earlier that you looked at Dr.
 8  Heiligenstein's violent aggressive behavior
 9  report from an epidemiological point of view,
10  right?
11            A.      Yes.
12            Q.      Was there anybody else charged
13  with that type of responsibility, in other words
14  to review reports or manuscripts with an eye
15  towards epidemiology?
16            A.      Before I answer that question,
17  I just would like to clarify.  I wasn't charged
18  with the responsibility to review his manuscript
19  or other manuscripts or -- I'm sorry, his report
20  or other reports.  So -- and I'm unaware of
21  anyone else being charged with the
22  responsibility, so the answer would be no.
23            Q.      If you weren't charged with the
24  responsibility of reviewing Dr. Heiligenstein's

                                                 Page 83

 1  report, how is it that you came to review it?
 2            A.      As I mentioned earlier, in a
 3  general perspective.  It's like a peer review
 4  process, if you have a -- if a journal receives a
 5  manuscript that's epidemiologically based or
 6  statistically based or based on a particular
 7  disease area, they're going to send it out to
 8  people that have background experience or
 9  training in that area to review that manuscript.
10  In a similar vein, I presume John respected my
11  scientific background enough to ask me to review
12  it.
13            Q.      Was there anybody else at Lilly
14  while you worked on Fluoxetine that had a
15  background in epidemiology that would be able to
16  review a report from that perspective?
17            A.      I believe so.  I think a lot of
18  the scientists at Lilly have general
19  methodological backgrounds and training that they
20  can think and evaluate a report and/or
21  manuscript, thinking about the basics of such a
22  study.
23            Q.      Was there anybody at Lilly that
24  if you wanted somebody to review a report or

                                                 Page 84

 1  manuscript from the epidemiological perspective
 2  that you would give the report to?
 3            A.      At that time or now?
 4            Q.      Let's start at that time.
 5            A.      There are so many good
 6  scientists at Lilly that think and approach
 7  problems from the scientific method, that I could
 8  think of hand fulls of them who I would ask to
 9  review a report I had written.
10            Q.      Who would be at the top of your
11  list?
12            A.      I suppose I would target the
13  report by the disease area it fell into as well
14  as some degree of the types of methods I
15  employed.
16            Q.      Let's start with depression.
17  Who would you go to if you wanted somebody to
18  look at it from an epidemiological perspective,
19  besides yourself?
20            A.      I suppose I would at least have
21  it reviewed by any one of the psychiatrists and
22  the statiscians.
23            Q.      The psychiatrists would be
24  people we talked about earlier, Dr.

                                                 Page 85

 1  Heiligenstein, Dr. Beasley and Dr. Wheadon?
 2            A.      Yes, if it were on depression.
 3            Q.      How about statisticians, which
 4  statisticians?
 5            A.      Again, the statisticians at
 6  Lilly are all very good, any one of them that had
 7  free time to be available to review it, I would
 8  have had them do it.
 9            MR. SMITH:  Are we reserving objections
10  as to the responsiveness of the answer and
11  self-serving comments in the answer?  We've got
12  to make them now.
13            MR. MYERS:  We're not reserving those,
14  all except as to form and responsiveness.
15            MS. LAWS:  At this deposition, we are
16  making objections to the form of the question and
17  responsiveness of the answer if they're not
18  waived.
19            MR. SMITH:  Are you the judge?
20            MS. LAWS:  We're just trying to clarify
21  the agreement.  We've been objecting to the form
22  and responsiveness of the answers in the
23  deposition.
24            MR. SMITH:  When they say all

                                                 Page 86

 1  scientists at Lilly are very good, that's a
 2  necessary type objection, even in Texas.
 3            MS. LAWS:  Well, you said I'm not the
 4  judge.
 5            MR. MYERS:  Go ahead.
 6            THE WITNESS:  I'm answering the
 7  questions as honestly as I can.
 8            Q.      With regards to statisticians,
 9  are there -- to your knowledge, was there a group
10  of statisticians that worked on Fluoxetine as
11  opposed to other products?
12            A.      I don't know the specific
13  answer to that, although I know some of the
14  statisticians have worked on Fluoxetine.  In
15  other words, I don't know if their sole
16  responsibilities were Fluoxetine or not.
17            Q.      Give me the names of the
18  statisticians you worked with on Fluoxetine?
19            A.      Mary Sailor, Ben Rampy, Greg
20  Enas, just for starters.
21            Q.      Any others?
22            A.      Well, there are a lot of
23  statisticians at Lilly, Charlie Sampson.
24            Q.      How about Bruce Dornseif?

                                                 Page 87

 1            A.      Bruce Dornseif, yes.
 2            Q.      Any others that you can think
 3  of?
 4            A.      That I worked with, not that I
 5  can think of right now.  I might as time goes on.
 6            Q.      Any others that you knew worked
 7  on Fluoxetine that you did not work with
 8  directly?
 9            A.      The only other name that comes
10  to mind is Doug Faries.
11            Q.      Can you spell the last name?
12            A.      I don't know how to spell it,
13  F-A-R-I-E-S, maybe, I'm guessing.
14            Q.      Is he still at Lilly?
15            A.      I think so.
16            Q.      Now, how about now, if you
17  wanted somebody to look at a report or manuscript
18  from an epidemiological standpoint who would you
19  go to now?
20            A.      Our particular health economics
21  research division has grown quite large and we
22  have recruited a lot of excellent scientists that
23  there are several within the company, within our
24  group, that I would ask to review it.

                                                 Page 88

 1            Q.      I'm still talking about
 2  Fluoxetine.
 3            A.      Oh, well, you said from an
 4  epidemiological perspective.  I certainly
 5  wouldn't count on the individuals I'm thinking of
 6  to review it from a disease specific approach
 7  necessarily.
 8            Q.      Is there anybody in your group
 9  now that you would go to with regards to
10  Fluoxetine and depression?
11            MR. MYERS:  To make the kind of review
12  you were talking about?
13            MS. ZETTLER:  Right, from an
14  epidemiological standpoint.
15            A.      Again, there are any number of
16  them from an epidemiological perspective I would
17  say I feel comfortable with their comments, but
18  if I wanted them to comment on the disease and
19  interpretation of those results, I certainly may
20  couple it with the psychiatrist.
21            Q.      Give me an idea of some people
22  you would go to now, some psychiatrists.
23            A.      Almost all of them.
24            Q.      Give me some names.

                                                 Page 89

 1            A.      Gosh.  Don Bushing, Tom Hughes,
 2  Lee Bowman, I mean just about anyone in our
 3  group.
 4            Q.      How many people of that nature
 5  in your group would have an epidemiological
 6  background?
 7            A.      Maybe five or so.
 8            Q.      Could you go through those
 9  names again?
10            A.      They're fairly new additions,
11  but Tom Hughes, Lee Bowman, Don Bushing, who else
12  did I say?
13            Q.      You went so fast, I didn't
14  catch it.
15            A.      That's just a few of them,
16  there are others.
17            Q.      Any of these people that you
18  know have responsibilities with regards to
19  Fluoxetine at this time, and I'm not talking
20  about Fluoxetine related just to depression?
21            A.      Yes.
22            Q.      Who?
23            A.      Don Bushing is one who is
24  assigned in our group to work on products in the

                                                 Page 90

 1  CNS and depression area, Dan Russell is working
 2  on a specific Fluoxetine project.
 3            Q.      When did Mr. Russell start
 4  working on a specific Fluoxetine project within
 5  your division?
 6            A.      He's working on managing an
 7  outside consultant to do a project for us.  It's
 8  actually a project that involves decision
 9  analysis.
10            Q.      Decision analysis.  What's
11  decision analysis?
12            A.      I would have to request that we
13  bring in a decision analyst to answer your
14  question, but it's essentially a process to frame
15  a problem, identify uncertanties about parameters
16  and use some statistical packages to incorporate
17  these parameters and uncertainties to make the
18  best decision possible.
19            Q.      And this is related to one
20  outside study?
21            A.      Once the contract is signed,
22  yes.
23            Q.      Is this study related to
24  Fluoxetine and suicide?

                                                 Page 91

 1            A.      No.
 2            Q.      Is it related to Fluoxetine and
 3  depression?
 4            A.      It's related to the cost
 5  effectiveness of Fluoxetine.
 6            Q.      In what context, cost
 7  effectiveness of prescribing Fluoxetine as
 8  opposed to other anti-depressants?
 9            A.      It looks at the -- it would
10  look at the -- depending on the design, and
11  obviously this is at the discretion of the
12  outside consultant groups.  Given that a contract
13  is signed, it would be looking at the cost
14  effectiveness of Fluoxetine presumably to other
15  anti-depressants.  But again, it's depending on
16  the design.
17            Q.      Is the potential cost of
18  litigation taken into consideration in this
19  study?
20            A.      No.  Again, though, that would
21  be dependent on the outside consultant group, but
22  I'm unaware of them having any plans to do
23  something like that.
24            Q.      Is this going to involve a

                                                 Page 92

 1  clinical trial administering Fluoxetine to
 2  patients?
 3            A.      No, it's a model new project.
 4            Q.      Modeling project?
 5            A.      Decision analysis modeling.
 6            Q.      You act like I know what you're
 7  talking about, and I don't.
 8            A.      You need to find a decision
 9  analyst to help you.
10            MR. SMITH:  What are decision analysts?
11            THE WITNESS:  Somebody who's been
12  trained in this methodology that I just described
13  to the level of my appreciation of it.
14            Q.      What would you call a study
15  like this, modeling project?
16            A.      I would describe it as a --
17  probably a retrospective study, but a model, yes.
18            Q.      To your knowledge, have any
19  other retrospective studies with regards to
20  Fluoxetine been performed by Lilly since you
21  became involved with the drug?
22            MR. MYERS:  Before he answers, let me
23  object to the form when you say other
24  retrospective studies, you mean studies like the

                                                 Page 93

 1  one he just told you about or any kind?
 2            MS. ZETTLER:  Any kind of a
 3  retrospective study.
 4            A.      That have been undertaken by
 5  Lilly?
 6            Q.      Anybody on Lilly's behalf, by
 7  Lilly or anybody on Lilly's behalf.
 8            A.      One could claim that the --
 9  when you use the term retrospective, it has
10  certain meanings.
11            Q.      Define retrospective for me,
12  what's a retrospective study?
13            A.      It's a study -- I think maybe
14  the simplest way to put it is it's a study that's
15  not prospective.  In other words, you do not
16  identify a number of patients or people to be
17  part of an ongoing prospective collection of
18  data, but you're using an existing data base or
19  an existing collection of data on patients that
20  you would analyze, and that's why I categorize
21  the modeling project under that.
22            Q.      Would you agree that Dr.
23  Beasley's meta-analysis report was based on a
24  retrospective analysis of information gathered

                                                 Page 94

 1  throughout clinical trials on Fluoxetine?
 2            A.      That's a prospective study,
 3  however a historical prospective study.  Some
 4  people would call them retrospective cohort
 5  analyses.  We're getting into semantics here and
 6  I don't know how much to help you.
 7            Q.      I want to be able to ask you
 8  questions so that you can understand them and
 9  give me as accurate an answer as possible, so I
10  guess we need to try to define some of these
11  terms.  What would be the difference between a
12  retrospective study, as you just defined it a
13  couple of minutes ago, and Dr. Beasley's
14  meta-analysis study?
15            A.      Well, there are different types
16  of retrospective studies, there are case control
17  studies, there are historical cohort studies, and
18  there are what I would call models as being part
19  of retrospective studies.  And of the three, I
20  would believe that a historical cohort or
21  historical prospective study is one of the
22  strongest because you're able to determine
23  incidence rates out of them.
24            Q.      So are you saying that Dr.

                                                 Page 95

 1  Beasley's meta-analysis report was based on data
 2  that had been and was currently being collected
 3  by Lilly with regards to suicidality?
 4            A.      Could you repeat that question,
 5  please?
 6            Q.      I guess I don't understand how --
 7  what was the pool of information that Dr. Beasley
 8  worked with when he wrote the meta-analysis?
 9            A.      Clinical trial data.
10            Q.      Clinical trial -- data from
11  clinical trials that had been completed or
12  clinical trials that were ongoing, or both?
13            A.      I do not recall the specific
14  patient population, I would need to review the
15  methods of the paper in order to answer your
16  question.
17            Q.      You worked on that paper,
18  didn't you?
19            A.      I think I mentioned I worked on
20  some parts of that project.
21            Q.      When you say that project, what
22  do you mean?
23            A.      Oh, from a methodological
24  standpoint my participation was defined from a

                                                 Page 96

 1  methodological standpoint.  Usually by asking
 2  questions such as what your definition of X or
 3  what is your -- you know, just methodological
 4  questions.
 5            Q.      So in other words, what's your
 6  definition of suicidal ideation, for instance?
 7            A.      Sure, that's all part of it.
 8            Q.      When you say asking what your
 9  definition, would somebody ask you what your
10  definition was or would you ask somebody else
11  what their definition was?
12            A.      It goes back to what we
13  discussed before about doing methodological
14  reviews of approaches to studies or reports that
15  people have written, it's just asking all the
16  fundamental basic questions.
17            Q.      What questions did Dr. Beasley
18  ask with regards to the meta-analysis report?
19            A.      I don't know if he asked me any
20  specific questions.  I'm only describing my
21  involvement based on your prior question.
22            Q.      So he would say -- for instance
23  he would say well, Dr. Kotsanos, I want to know
24  if there was a greater incidence of suicidal

                                                 Page 97

 1  ideation on people who had previous suicidal
 2  ideation, would it be that type of thing or --
 3  because I don't understand what you mean when you
 4  say asking questions.
 5            A.      It's just part of the
 6  scientific approach to any study, just
 7  identifying all the fundamental components of a
 8  study up front.  It was a team approach and team
 9  discussion to the approach to any analysis or any
10  study.
11            Q.      What were the fundamental
12  components of Dr. Beasley's study?
13            A.      Again, it's been several years
14  since I worked on it.  I think it's just fair to
15  say that it goes back to a general approach to
16  always thinking about the basics in doing any
17  type of study or writing a report.
18            Q.      What are the basics?
19            A.      The scientific method is making
20  sure you have an introduction, a method section,
21  a result section and a discussion section.
22            Q.      I think you're not being very
23  responsive at all here.
24            MR. MYERS:  Go ahead and ask him

                                                 Page 98

 1  another question and see.
 2            MS. ZETTLER:  I think he can be
 3  responsive, I just don't think he is being
 4  responsive.
 5            MR. MYERS:  The problem may be with the
 6  question.
 7            MS. ZETTLER:  I think he's taking it
 8  way too broad.
 9            A.      For example, if you wanted to
10  say well, the introduction ultimately has a
11  review of the -- it frames the issue, has a
12  review of the literature, is there significant
13  rationale to undertake what's being undertaken,
14  what are the objectives, are the objectives clear
15  enough, are they specific enough, can they be
16  answered by the design that's put forward.  Then
17  let's look at the design, is the design clear
18  enough such that it would ultimately answer the
19  objectives or hypothesis of the study, those
20  types of questions.  And I think it's just a
21  process and a methodological approach.
22            Q.      Do you recall what the
23  objectives of Dr. Beasley's study were?
24            A.      Vaguely, but I would feel more

                                                 Page 99

 1  comfortable reviewing it.
 2            Q.      Give me what your recollection
 3  is on what the objectives were?
 4            A.      I cannot quote for you verbatim
 5  the objectives or the study hypothesis, but there
 6  was a look for an association of suicidality in
 7  depressed patients who were on Fluoxetine or
 8  Tricyclics or on placebo therapy.
 9            Q.      Was that the only objective, in
10  other words to compare those three groups, or was
11  there analyses of the incidence of suicidality in
12  Fluoxetine alone also?
13            A.      That could have been one of the
14  stated objectives, I do not recall, although that
15  would be tied into the evaluation of an
16  association because one would be looking at the
17  incidence rates.
18            Q.      Do you remember what the
19  patient population was that was studied in that
20  report?
21            A.      I cannot give you the specific
22  population, although I know it involved clinical
23  trials of Fluoxetine, clinical trial patients on
24  Fluoxetine.

                                                 Page 100

 1            Q.      Okay.  Is it your understanding
 2  that during the period of time where Dr.
 3  Beasley's report was being generated that
 4  Fluoxetine was being studied with patients
 5  suffering from various diseases, not just
 6  depression?
 7            A.      I'm sorry, can you repeat that
 8  one more time?
 9            Q.      Sure.  Is it your understanding
10  that during the time when Dr. Beasley's report
11  was being written, worked on, that Fluoxetine was
12  being studied for treatment of diseases or
13  syndromes other than depression?
14            A.      By your question, are you
15  asking were other clinical trials ongoing
16  evaluating Fluoxetine in the use in other
17  disorders besides depression?
18            Q.      Right, but not just ongoing,
19  that had been completed and were ongoing.  In
20  other words, Fluoxetine was being studied for use
21  with obesity; correct?
22            A.      Uh-huh.
23            Q.      You have to say yes or no.
24            A.      Yes, I'm sorry.

                                                 Page 101

 1            Q.      Obsessive-compulsive disorder?
 2            A.      Yes.
 3            Q.      Bulimia nervosa?
 4            A.      Yes.
 5            Q.      Alcoholism?
 6            A.      I think so, but I cannot recall
 7  exactly.
 8            Q.      Smoking cessation?
 9            A.      Yes.
10            Q.      A whole bunch of different
11  diseases other than depression; correct?
12            A.      Yes.
13            Q.      Or conditions?
14            A.      Yes.
15            Q.      I don't know if you want to
16  call smoking a disease.
17            MR. SMITH:  It would speak more in
18  light of obsessive-compulsive.
19            Q.      To your memory, in Dr.
20  Beasley's report, were people in clinical trials
21  related to those other indicated uses taken into
22  consideration as part of the patient population,
23  or was it just limited to depression?
24            A.      For the specific meta-analysis,

                                                 Page 102

 1  I believe the population were depressed patients,
 2  but I would want to review that paper just to
 3  make sure my answer is completely accurate.
 4            Q.      Okay.  So to your knowledge or
 5  to your memory, the patient population included
 6  depressed patients in clinical trials?
 7            A.      Yes.
 8            Q.      Okay.  Do you know if any
 9  spontaneous reports of adverse events were taken
10  into consideration in the analysis?
11            A.      Do you mean for the
12  meta-analysis paper?
13            Q.      Right.
14            A.      Because this was a clinical
15  trial, I believe the attempted suicides or
16  suicides were identified, some through adverse
17  event reports, others through the mechanism by
18  which they define, additional ways of defining
19  suicidality.
20            Q.      Okay.  Maybe my question wasn't
21  clear.  Do you have an understanding as to what a
22  spontaneous adverse event report is?
23            A.      I believe I have an
24  understanding, although I couldn't give you a

                                                 Page 103

 1  regulatory definition for it.
 2            Q.      Okay.  What is your
 3  understanding of what a spontaneous adverse event
 4  report is?
 5            A.      Well, interpretation of a
 6  spontaneous adverse event report is very broad
 7  and that is any event the patient mentions in
 8  relation to a therapy they had or have been
 9  taking.
10            Q.      In Dr. Beasley's study, the
11  meta-analysis, were adverse events that were
12  reported by people outside of the clinical trial
13  process considered?  In other words, after the
14  drug was on the market, and a patient or patients
15  reported that they suffered an adverse event,
16  were those types of adverse events or those
17  sources of adverse events taken into
18  consideration?
19            A.      Again, I would feel more
20  comfortable reviewing the manuscript, however I
21  believe the study was done with that clinical
22  trial population and the data collected during
23  that clinical trial, whether they were Ham-D
24  analyses or reports of adverse events or suicide

                                                 Page 104

 1  attempts or actual suicides.
 2            Q.      Okay.  Clinical trials that
 3  were taken into consideration, were those
 4  strictly United States clinical trials or were
 5  those international clinical trials also?
 6            A.      Again, regarding the
 7  manuscript, I must defer to my prior statement,
 8  it was, as I recall, just U.S. clinical trials.
 9            Q.      Why were the international
10  clinical trials not taken into consideration, if
11  you know?
12            A.      My involvement did not go
13  beyond the U.S. clinical trial data analysis.  I
14  cannot comment specifically on international
15  populations being included in the study.
16            Q.      Did you have any understanding
17  as to why the international studies were not
18  taken into consideration?
19            A.      I recall them being taken into
20  consideration, the international trials, although
21  I cannot give you any specifics because I do not
22  know any specifics about the evaluation of
23  international, outside of U.S. data, versus just
24  U.S. data.

                                                 Page 105

 1            Q.      So now your testimony is that
 2  they were taken into consideration in the
 3  meta-analysis article by Dr. Beasley?
 4            MR. MYERS:  Before he answers, let me
 5  object to the form because you mischaracterized
 6  his testimony.  He just testified a minute ago
 7  that they were taken into consideration, and two
 8  minutes ago he testified that the patient
 9  population included on U.S. clinical trials.  So
10  I think maybe the problem is in your definition
11  of taken into consideration, and that's where the
12  breakdown is.
13            Q.      Okay, let's go on.  When you
14  said taken into consideration, what do you mean?
15            A.      There were a number of clinical
16  trials of Fluoxetine undertaken, both in the U.S.
17  and outside of the U.S.
18            Q.      Okay.
19            A.      And the meta-analysis paper had
20  obviously the U.S. population, and at the time of
21  my involvement I know that there was discussion
22  to work on the international data, although I was
23  not involved in that component.
24            Q.      When you say work on

                                                 Page 106

 1  international data, what do you mean?
 2            A.      Again, it's been a while and I
 3  was not involved in that particular part of the
 4  project, but I believe there were discussions on
 5  doing similar analyses with international data,
 6  and I don't know the feasibility and issues that
 7  were discussed at that time because I wasn't
 8  involved in those discussions.
 9            Q.      To your knowledge, was the
10  international data collected for review with
11  regards to the meta-analysis study?  In other
12  words, if Dr. Beasley had decided to do an
13  analysis of the international clinical trial data
14  in support of his paper, would that information
15  have been available to him?
16            MR. MYERS:  This is a hypothetical now?
17            MS. ZETTLER:  Right.
18            MR. MYERS:  At what point in time?
19            MS. ZETTLER:  When he was working on
20  the paper.
21            MR. MYERS:  He who, he, Dr. Kotsanos or
22  or Dr. Beasley?
23            MS. ZETTLER:  Dr. Beasley.
24            A.      I do not know how readily

                                                 Page 107

 1  available the feasibility and the practicality of
 2  assembling international data.  At that time the
 3  U.S. study as ongoing, but I do not know Charles'
 4  thought process and everything that he undertook
 5  while doing that.
 6            Q.      Was the U.S. clinical trial
 7  data collected in a data base at Lilly?
 8            A.      The U.S. clinical trial data
 9  were on a data base at Lilly, yes, I believe.
10            Q.      And what was the purpose of
11  putting that data on a data base?
12            A.      That's a hard question for me
13  to answer because I believe it's necessary to
14  have your data assembled in some fashion,
15  computerized fashion, for analyses of safety and
16  efficacy as part and parcel of clinical trials.
17            Q.      Okay.  How about the
18  international clinical trials, wouldn't you want
19  to collect the data for the same reason?
20            A.      Because I didn't have any
21  involvement in the international trials or how
22  the data were collected or where they existed, I
23  don't know the answer to your question because I
24  don't know how they existed.

                                                 Page 108

 1            Q.      For what reasons would they
 2  perform clinical trials outside the U.S. other
 3  than to collect data with regards to the study
 4  drug?
 5            A.      For submission to other foreign
 6  countries for approval of the drug in that
 7  particular country.
 8            Q.      Okay.  So the clinical trials
 9  would be run country specific?
10            MR. MYERS:  I object to the form, what
11  do you mean by country specific?
12            MS. ZETTLER:  For submission -- for the
13  information to be submitted to a regulatory
14  agency for that particular country.
15            A.      It may be, sure.
16            Q.      To your knowledge, is there
17  some reason why Dr. Beasley wouldn't or couldn't
18  analyze the international clinical trial data in
19  support of his meta-analysis article?
20            MR. MYERS:  Before he answers, let me
21  object to the form because it assumes Dr. Beasley
22  would not or could not do that and I don't know
23  that there's been any testimony that he would or
24  could not by this witness.

                                                 Page 109

 1            A.      I don't know.
 2            Q.      Let's talk about outpatient
 3  population again as it relates to Dr. Beasley's
 4  article.  I think you've testified that there's a
 5  broad category of depressed patients in clinical
 6  trials; correct, that was the broad category with
 7  regards to the patient population that Dr.
 8  Beasley looked at?
 9            A.      Help me with the use of the
10  term broad category, do you mean more than just
11  depressed patients but other disorders as well or --
12            Q.      No, let me -- if I
13  mischaracterize your testimony, please tell me
14  that I'm mischaracterizing it, but my
15  understanding of your testimony earlier is that
16  at least part of the components of the patient
17  populations that Dr. Beasley looked at were
18  clinical trial participants who were suffering
19  from depression; correct?
20            A.      Yes.
21            Q.      Other than those two fairly
22  broad categories, do you remember any other
23  elements of the patient population?  In other
24  words, did they have to be in double-blind

                                                 Page 110

 1  placebo controled studies?
 2            A.      Again, that would pertain to
 3  the methods of the paper and the methods of the
 4  analyses defining which protocols or studies
 5  would be part of an analysis, a meta-analysis,
 6  and clearly all that would need to be defined in
 7  advance.  I would be guessing to say yes or no
 8  without reviewing, again, the paper.
 9            Q.      Other than the broad categories
10  of depressed clinical trial participants, do you
11  recall any other elements of the patient
12  population that narrowed it down at all?
13            MR. MYERS:  I object to the form,
14  narrowed it down to what, from where to where?
15            MS. ZETTLER:  Narrowed it down from the
16  broad categories of clinical trial participants
17  who were suffering from depression.
18            A.      I believe they were controlled
19  trials, which means that there was always more
20  than one treatment arm.
21            Q.      Okay.
22            A.      And probably a number of other
23  factors such as ones you mentioned, but I would
24  want to review the methods before I could

                                                 Page 111

 1  actually answer that.
 2            Q.      Are you familiar with what
 3  exclusion criteria are in protocols?
 4            A.      You mean in the depression
 5  protocols?
 6            Q.      Just in general, what the term
 7  exclusion criteria means?
 8            A.      I'm familiar with that, yes.
 9            Q.      Are you aware that in some of
10  the depression trials at least one of the
11  exclusion criteria was anybody that was a serious
12  suicidal risk?
13            MR. MYERS:  I object to the form only
14  to the extent that I don't know that that's a
15  precise use of terminology.
16            MS. ZETTLER:  It is.
17            MR. MYERS:  Same objection.
18            A.      Could I have you repeat it one
19  more time?
20            Q.      Sure.  Are you aware that in at
21  least some of the clinical trials that were
22  performed on Fluoxetine, one of the exclusion
23  criteria was anyone who was a serious suicidal
24  risk?

                                                 Page 112

 1            MR. MYERS:  Same objection, go ahead
 2  and answer it if you can.
 3            A.      It's been a while since I
 4  remember discussing the methods of this paper,
 5  and then the exclusion criteria of each of the
 6  individual protocols.  I vaguely seem to recall a
 7  discussion along those lines, although I would
 8  think that particular issue would be a matter of
 9  medical judgment of each investigator if in fact
10  it existed.
11            Q.      What I'm trying to find out is
12  if Dr. Beasley narrowed his study down to people
13  who were included in clinical trials suffering
14  from depression, and then fell under another
15  criteria.  In other words, we talked about
16  controlled trials, participated in controls
17  trials.  Were there any other factors that were
18  taken into consideration to narrow down that
19  patient population for the study?
20            MR. MYERS:  Before he answers, let me
21  object to the form to the extent you're asking
22  him what Dr. Beasley considered.  Since it's Dr.
23  Beasley's paper and not his paper, it may call
24  upon him to speculate.

                                                 Page 113

 1            Q.      And this witness has already
 2  testified that he was asked to review that paper
 3  from an epidemiological standpoint, and part of
 4  epidemiology is working with patient populations;
 5  correct, Dr. Kotsanos?
 6            A.      I would like to clarify.  I
 7  don't recall saying I was asked to review the
 8  paper from an epidemiological standpoint, I
 9  remember saying that for the Heiligenstein paper
10  or report.  In this case, I think I mentioned
11  that I was involved in part of the project and I
12  was involved in working through the approach to
13  the problems, and I don't believe I was ever a
14  formal or even informal reviewer of Dr. Beasley's
15  paper for submission.
16            Q.      Okay.  Would you agree that the
17  results of a study can be changed by virtue of
18  studying a different patient population?  In
19  other words, the results of the study that you
20  look at for a patient population that includes an
21  A criteria may be different than the patient
22  population that includes a B criteria?
23            A.      On a general theoretical
24  ground, I would have to say with that general

                                                 Page 114

 1  type of question, possibly, but without specifics
 2  it's hard for me to answer any particular
 3  question.
 4            Q.      Well, for instance, say you
 5  were studying the incidence of suicidality on
 6  patients on Fluoxetine against patients who were
 7  taking Imiprimine, the results of that study
 8  would be different than or at least theoretically
 9  would be different than a study comparing
10  Fluoxetine with Elavil; correct?
11            A.      That's a very theoretical
12  question, it's hard for me to answer.  I'm having
13  a hard time giving you an answer on that one.
14            Q.      Would you agree that various
15  drugs have different adverse events that are
16  associated with them?
17            A.      In general, I agree that drugs
18  can have different adverse event profiles than
19  each other, yes.
20            Q.      And part of the reason that you
21  do a study, a comparitor study, with the drug
22  like Fluoxetine and another anti-depressant is to
23  determine the differences and efficacy and safety
24  between those two drugs; correct?

                                                 Page 115

 1            A.      If those are the study
 2  objectives, then, yes.
 3            Q.      So if Dr. Beasley were to do a
 4  meta-analysis of patients on Fluoxetine as
 5  compared with patients on placebo, and a
 6  particular tricyclic, not a group of tricyclics,
 7  the results of the study as far as a comparison
 8  of percentages of various adverse events may vary
 9  if you were to compare it with another tricyclic?
10            MR. MYERS:  Let me object to the form
11  only to the extent of what Dr. Beasley would or
12  wouldn't do because I think that would call on
13  him to speculate as to how Dr. Beasley would
14  conduct the study.
15            A.      I seem to recall on this
16  particular meta-analysis, each particular
17  protocol were analyzed individually of each
18  other.
19            Q.      For what purpose?
20            A.      For one of the primary outcomes
21  that I stated, I believe to be the primary focus
22  of the meta-analysis, and I think that's part of
23  the paper.  But again, I need to review that.
24            Q.      What was the primary focus of

                                                 Page 116

 1  Dr. Beasley's paper again?
 2            A.      As I recall, without having
 3  reviewed it again, he was looking at the
 4  association of suicidality between treatment
 5  groups.
 6            Q.      Okay.  And those treatment
 7  groups were Fluoxetine placebo and tricyclics?
 8            A.      Right.
 9            Q.      When you say each protocol was
10  analyzed individually, what do you mean?
11            A.      You can pull all the protocols
12  together and get a larger sample size and look at
13  the outcome, and then you can separate out each
14  study and look at them individually as well, and
15  I believe the paper actually reported on both
16  methods.  So addressing your specific question
17  about, you know, breaking out the tricyclics as a
18  group in the individuals, I think that was done
19  in the paper, but I would need to review it.
20            Q.      But the protocols that were
21  reviewed were strictly protocols that compared
22  Fluoxetine placebo and tricyclics; correct?
23            A.      One protocol would, for
24  example, compare Fluoxetine and a particular

                                                 Page 117

 1  tricyclic, another protocol may do Fluoxetine and
 2  placebo, another protocol may do Fluoxetine, a
 3  specific tricyclic and placebo.  So there were
 4  multiple protocols.
 5            Q.      The protocols that include at
 6  least two of those three criteria or three
 7  groups?
 8            A.      Again, I would need to review
 9  the paper, but they were controlled trials where
10  at least they had one other treatment arm.  So it
11  could have been a placebo or could have been a
12  tricyclic.
13            Q.      Okay.  What's --
14            MR. SMITH:  I'm sorry, motion for
15  sanctions.
16            (DISCUSSION OFF THE RECORD.)
17            Q.      Could the size of the sample
18  make a difference in the results?
19            MR. MYERS:  I object to form, which
20  sample?
21            MS. ZETTLER:  The patient sample.
22            A.      You mean in the meta-analysis
23  of the Beasley paper or other studies?
24            Q.      Let's take it generally in any

                                                 Page 118

 1  study, is there a potential difference in the
 2  results that correlates to the size of the
 3  sample?
 4            A.      There's a certain statistical
 5  procedure that's undertaken to calculate a sample
 6  size required for the studies, and if you want me
 7  to walk you through that, I would actually defer
 8  you to a statistician, but there's an approach
 9  that's used to size a study.
10            Q.      Do you recall what approach was
11  used in Dr. Beasley's article?
12            A.      I do not for that particular
13  one.
14            Q.      When you said earlier that you
15  recall that there was an analysis of all of the
16  protocols pooled --
17            A.      Uh-huh.
18            Q.      -- as well as an individual
19  analysis of the protocols?
20            A.      Uh-huh.
21            Q.      When you say individual
22  analysis of protocols, are you saying that all of
23  the Fluoxetine placebo trials were analyzed as
24  one?

                                                 Page 119

 1            A.      I seem -- again, I really want
 2  to look at the paper again, but I seem to recall
 3  that in the final paper that there was a report
 4  of each individual protocol, but I would need to
 5  look at that again.
 6            Q.      Do you remember how many
 7  protocols were involved in that?
 8            A.      More than a dozen, fifteen,
 9  sixteen, seventeen, I don't remember the exact
10  number.
11            Q.      More than twenty?
12            A.      I don't remember the exact
13  number.
14            Q.      Okay.  More than fifty?
15            MR. MYERS:  He said he didn't know.
16            MS. ZETTLER:  I'm trying to refresh his
17  recollection.
18            MR. MYERS:  Let me just say this:  As
19  relates to the paper, if you have the paper there
20  it might help this along if you show him the
21  paper.
22            MS. ZETTLER:  I'm asking for his
23  recollection.
24            MR. MYERS:  Then he has to give you the

                                                 Page 120

 1  caveat that he's got to see the paper, I think.
 2            MS. ZETTLER:  That's fine.
 3            A.      Okay.  As long as you don't
 4  mind, I don't mind.
 5            Q.      Do you have a recollection if
 6  it was more than fifty trials that were taken
 7  into consideration?
 8            A.      I gave you an idea where I
 9  thought it was, but without looking at the paper --
10            Q.      Somewhere between fifteen and
11  twenty?
12            A.      Yes, but without looking at the
13  paper, it's hard for me to recall.
14            Q.      Do you have any knowledge of
15  how many clinical trials were run on Fluoxetine
16  world wide with regards to depression?
17            A.      I do not recall that.
18            Q.      Do you know if it was more than
19  a hundred?
20            A.      I don't know that.
21            Q.      Do you know with regards to Dr.
22  Beasley's paper if any other indicated uses were
23  involved other than depression?
24            A.      Repeat that again, I'm sorry, I

                                                 Page 121

 1  was distracted.
 2            Q.      Do you know with regards to Dr.
 3  Beasley's paper, were any other indicated uses
 4  involved, any trials on any other indicated uses,
 5  like we talked about earlier, obesity, bulemia,
 6  things of that nature?
 7            A.      Used for what purpose?
 8            Q.      As part of Dr. Beasley's
 9  meta-analysis.
10            A.      I believe the meta-analysis
11  focused on depressed patients.
12            Q.      Was Dr. Beasley's meta-analysis
13  manuscript article a result of a report that was
14  written for the purposes of submission to a
15  regulatory agency?
16            A.      The manuscript came about as
17  work done on submission of an analysis to a
18  regulatory agency.
19            Q.      Was that submission related to
20  the advisory committee meeting in September of
21  1991?
22            A.      I believe the submission of the
23  suicidality report to the FDA came before there
24  was an advisory committee meeting scheduled, but

                                                 Page 122

 1  I don't recall for certain.
 2            Q.      Okay.  Would the parameters of
 3  the patient population that Dr. Beasley worked
 4  with in the meta-analysis, would that be set out
 5  in the paper itself?
 6            A.      Whatever objectives and
 7  analyses were planned would be in the paper, yes,
 8  should be.
 9            Q.      So in other words he would say
10  something to the effect of so many patients from
11  double-blind placebo controlled clinical trials
12  were analyzed for purposes of blah blah blah?
13            A.      That's correct.
14            MR. MYERS:  That was a for instance?
15            MS. ZETTLER:  The blah blah blah part
16  especially, Larry.
17            A.      I should be careful how I
18  respond to blah blah blahs.
19            Q.      Did you work on any reports for
20  regulatory agencies specifically related to
21  suicidality and the use of Fluoxetine, other than
22  the quarterly statements, safety reports, that we
23  talked about earlier?
24            A.      Again, I was involved in the

                                                 Page 123

 1  quarterly safety reports, but to restate,
 2  typically the psychiatrist reviewed those
 3  components that you mentioned.
 4            Q.      Okay.
 5            A.      And also, again I was involved
 6  in the meta-analysis, some part of project as
 7  we've been over.
 8            Q.      So the part of that project
 9  that was reported to the FDA at some period of
10  time you worked on that also?
11            A.      Right.  That was in the very
12  up-front component, the very thought process and
13  planning.
14            Q.      Okay.  So it was more of a
15  matter of setting up the objectives and goals of
16  the study as opposed to actually analyzing data?
17            A.      Methodological approach,
18  correct.
19            Q.      Other than those two things we
20  talked about, did you work on anything else with
21  regards to suicidality?
22            A.      The paper that -- or the letter
23  to the editor of the American Journal of Public
24  Health, that one.

                                                 Page 124

 1            Q.      Did that stem from a report to
 2  the FDA?
 3            A.      I don't believe it did, I think
 4  it was just a component of additional analyses we
 5  were undertaking to get a better picture of what
 6  was going on.
 7            Q.      Other than those things that we
 8  just talked about, did you work on anything else
 9  at Lilly for purposes of reporting to a
10  regulatory agency that dealt with Fluoxetine and
11  the issue of suicidality?
12            A.      Just signing off on sixteen
13  thirty-nines or adverse event reports, and I
14  believe that probably covers it, although to the
15  best of my recollection at this time.
16            Q.      Are you aware of any ongoing
17  studies with regards to Fluoxetine at this time?
18            MR. MYERS:  Any?
19            MS. ZETTLER:  Any.
20            MR. MYERS:  Any.
21            MS. ZETTLER:  Any.
22            A.      I do not know what kind of
23  ongoing studies, if any, are taking place for
24  Fluoxetine.

                                                 Page 125

 1            Q.      Okay.
 2            A.      I do know, and I presume you
 3  mean clinical trials?
 4            Q.      Start with clinical trials.
 5            A.      Clinical trials, and that's my
 6  answer, I do not know.  But obviously this cost
 7  effectiveness modeling project I'm aware of,
 8  which is ongoing through our group.
 9            Q.      How about any papers that are
10  in the works, any manuscripts, do you know of any
11  manuscripts in the works at this time regarding
12  Fluoxetine?
13            A.      I'm unaware of any manuscripts
14  in the works, although this triggered my thought
15  to your former question.  There are some other
16  trials I'm aware of that are not -- there again,
17  these cost effectiveness and different outcome
18  projects that are ongoing, one with a large
19  health maintenance organization in the northwest.
20            Q.      What do you mean when you say
21  different outcomes?
22            A.      Well, outcomes in addition to --
23  actually I don't know the specific objectives of
24  the study that's ongoing to the health

                                                 Page 126

 1  maintenance organization, although I do know that
 2  they're looking at cost effectiveness and quality
 3  of life as two of their outcomes.
 4            Q.      What do you mean when you say
 5  quality of life?
 6            A.      Quality of life is a very
 7  holistic approach to patients which looks at more
 8  than just physical, mental and social function,
 9  it looks at patient well-being.  There are
10  different survey devices used to measure quality
11  of life of patients.
12            Q.      Is that something that's
13  included in efficacy and safety studies on drugs?
14            A.      Although I'm sure this point is
15  debatable, one could argue that quality of life
16  is an additional efficacy measure, but that's
17  open for scientific debate.
18            Q.      I guess I don't understand what
19  you mean by quality of life as it applies to
20  Fluoxetine.  Is it something that's above and
21  beyond curing of depression or treating of
22  depression or is it something that's intrinsic in
23  the treatment of the disease that it's prescribed
24  for?

                                                 Page 127

 1            A.      Clearly there are a number of
 2  outcomes of the disease one can measure, and a
 3  disease has impact on a patient, many different
 4  kinds of impact.  And one can measure, and does
 5  measure, certain -- and this is in general, this
 6  discussion, certain defined outcomes which may
 7  answer a particular question.  They can add
 8  outcomes such as quality of life to look at a
 9  broader picture of the impact of interventions on
10  the impact of the disease on the patient.  So
11  that ultimately a health care provider has more
12  information about a disease and the impact
13  certain therapies have on the disease so that
14  they can make the best decision they can with all
15  of this information.  Quality of life is just one
16  additional outcome measure that's been looked at
17  lately, cost effectiveness are others, to change
18  an environment out there that triggers these
19  additional outcome studies.
20            Q.      Are you saying comparing the
21  use of Fluoxetine as opposed to, say,
22  psychotherapy?
23            MR. MYERS:  Are you asking if that's
24  what they're doing or are you asking for an

                                                 Page 128

 1  example?
 2            MS. ZETTLER:  For an example.
 3            A.      One could think of any
 4  examples.  One could probably think of any
 5  example, but then it would be a question of is it
 6  a feasible study and does if make sense, I would
 7  have to go through the whole thought process to
 8  figure out the type of study you would want to
 9  do.
10            Q.      Give me an example of the
11  quality of life as an outcome on a study.
12            A.      There are many domains of
13  quality of life.  There are physical function
14  domains.  For example, what are the activities of
15  daily living of the patient, can they button
16  their buttons and get dressed by themselves in
17  the morning, can they walk, can they run, thus
18  can they exercise.  There are social function
19  domains, what is their interpersonal relations,
20  their friendships, there are emotional domains of
21  quality of life, such as anxiety, stigma,
22  perception of their disease.  There's symptoms
23  that contribute to domains of quality of life,
24  such as pain, pain is a big one.  So outcomes

                                                 Page 129

 1  could look at any one of those domains or all of
 2  them collected together and one could make
 3  comments on these domains of quality of life,
 4  it's a very holistic look at patient care.
 5            Q.      In the study that described
 6  this, it was somewhere out west, northwest?
 7            A.      Uh-huh.
 8            Q.      Do you know what domains of
 9  quality of life they're looking at?
10            A.      Again, I'm -- it's a grant
11  study.  So we don't have any control over the
12  design of the study, in fact I've never seen the
13  protocol, the final protocol, but in some of the
14  initial discussions and preliminary protocols, I
15  recall them mentioning quality of life as an
16  outcome.  But whether or not they're actually
17  doing that in the actual study, I don't know
18  because I haven't seen the final protocol from
19  them.
20            Q.      Do you remember any specifics
21  about the quality of life that they were looking
22  at or is it quality of life in general?
23            A.      There are different types of
24  quality of life.  I don't know, the answer is I

                                                 Page 130

 1  don't know, but there are different types of
 2  quality of life, just general quality of life to
 3  each specific quality of life questions.  And we
 4  could probably spend a week talking about quality
 5  of life.
 6            Q.      Are you familiar with a man
 7  named Peter Kramer?
 8            A.      I'm familiar, I believe I'm
 9  familiar with that name, Peter Kramer.
10            Q.      Are you familiar with his book,
11  Listening to Prozac?
12            A.      I'm familiar he wrote that
13  book, I've never read the book.
14            Q.      Do you have an understanding of
15  what the subject matter of the book is?
16            A.      Aside from reading newspapers,
17  I don't have a good feel for what his premise
18  was.
19            Q.      When you say that the study of --
20  the quality of life study is a grant study, what
21  do you mean?
22            A.      It means that we provide the
23  funding to an outside agency as a grant, and then
24  they're responsible for the design,

                                                 Page 131

 1  implementation, analysis and reporting of the
 2  data.
 3            A.      What's the outside agency
 4  that's involved in the quality of life study?
 5            A.      It's a health maintenance
 6  organization.
 7            Q.      HMO?
 8            A.      Yes.
 9            Q.      Do you know what group or
10  hospital it's connected to, if any?
11            A.      Yes, I do.
12            Q.      Who is it, what is it?
13            A.      It's Group Health Cooperative.
14            Q.      Okay.  Other than the cost
15  effectiveness model we talked about earlier and
16  the quality of life study, are you aware of any
17  other ongoing studies with regards to Fluoxetine
18  at this time?
19            A.      One other study, and I don't
20  know the status of the study, I don't know if
21  it's still ongoing, but it's -- I believe it's an
22  overdose study conducted at -- I don't remember
23  the investigator's name, I'm sorry.
24            Q.      Is it an institutional study or

                                                 Page 132

 1  is it an outpatient study, inpatient or
 2  outpatient study?
 3            A.      I don't know the details of the
 4  study.
 5            Q.      What are the objectives, do you
 6  know?
 7            A.      I don't know those either.
 8            Q.      Do you know if there's a
 9  comparitor drug involved?
10            A.      I don't know the design of the
11  study.
12            Q.      Okay.  How is it that you're
13  familiar with the study?
14            A.      I was involved in discussions
15  in the very beginning of my time working on
16  Prozac, and even before then, of design of a
17  descriptive overdose study, but -- and I know
18  that one is ongoing, but how that design of the
19  study evolved and took place over time, not being
20  directly involved in it, I don't know the
21  details.
22            Q.      Do you know what area of the
23  country this is being performed in or areas?
24            A.      That's a good question.  I

                                                 Page 133

 1  don't know how many centers are participating in
 2  this and where they're located, but I'm pretty
 3  sure it's just a U.S. study.
 4            Q.      Do you know whether or not it's
 5  a single or multi-center study?
 6            A.      Again, I don't know.
 7            Q.      Okay.  Do you know who at Lilly
 8  is working on this study in-house?
 9            A.      It was John Heiligenstein.
10  Whether or not he's still overseeing it, I don't
11  know.
12            Q.      Are you familiar with the term
13  rechallenging?
14            A.      You mean regarding
15  pharmaceutical use?
16            Q.      Right.
17            A.      Yes.
18            Q.      What does that mean with
19  regards to pharmaceutical use?
20            A.      To me it means administering
21  drug to a patient, stopping the administration,
22  and then over a period of time, however defined,
23  placing them on the medication again.
24            Q.      For what purpose?

                                                 Page 134

 1            A.      I guess that can vary, but
 2  looking at the affect of the drug on the patient.
 3            Q.      Okay.  Have you heard of the
 4  phrase rechallenging as it relates to adverse
 5  events?
 6            A.      Well, sure, I've heard the
 7  expression.
 8            Q.      Okay.  How would you utilize
 9  rechallenging with regards to adverse events?
10            A.      During my years at Lilly and
11  signing off on adverse event reports, I saw
12  reports for different drugs, patients that were
13  on the drug developed an event, whatever, the
14  drug was stopped, the event may or may not have
15  resolved, and started back on and persisted,
16  worsened, whatever.
17            Q.      Okay.
18            MR. MYERS:  Excuse me.
19            (DISCUSSION OFF THE RECORD.)
20            Q.      Are you aware of any
21  rechallenging studies that were performed with
22  regards to Fluoxetine?
23            A.      None that I'm aware of.
24            Q.      Are you aware of any

                                                 Page 135

 1  rechallenging studies that were considered with
 2  regards to Fluoxetine?
 3            A.      I'm aware of discussions that
 4  took place.
 5            Q.      Okay.  Were you involved in
 6  those discussions?
 7            A.      Peripherally, not directly.
 8            Q.      What was your involvement in
 9  those discussions?
10            A.      I think I mentioned routine
11  meetings to you where we presented status of our
12  projects, and I seem to recall discussions taking
13  place, although my exposure was brief and
14  limited.
15            Q.      Okay.  Are you aware that the
16  FDA personnel suggested to Eli Lilly personnel
17  that a rechallenging study be done with regards
18  to Fluoxetine and suicidal ideation?
19            MR. MYERS:  Before he answers, let me
20  object to the form to the extent it assumes a
21  fact that I don't think would be in evidence in
22  this case, and I also object to the form and the
23  use of the term suggest as being awfully vague.
24  But if you can answer, go ahead.

                                                 Page 136

 1            A.      I'm trying to recall whether or
 2  not any were suggested.  I remember vaguely
 3  discussions about it, but I don't recall
 4  specifically if there was any written request or
 5  verbal request to do that.  But vaguely, it
 6  seemed like there were discussions, but I don't
 7  recall any more than that.
 8            Q.      There were discussions
 9  regarding an FDA request that a rechallenge study
10  be performed?
11            A.      Vaguely it seems there were
12  some discussions along those lines, but I don't
13  remember any specifics.
14            Q.      Okay.
15            MS. ZETTLER:  Let's take a lunch break.
16             (A LUNCH BREAK WAS TAKEN.)
17            Q.      Before we went to lunch we were
18  talking about a rechallenge protocol, a
19  rechallenge study, that you said you had some
20  vague memory of it being requested by the FDA to
21  perform; is that correct?
22            A.      I said I had a vague memory of
23  a discussion about it.
24            Q.      To your knowledge was a

                                                 Page 137

 1  rechallenge study ever done on Fluoxetine?
 2            A.      Not that I'm aware of.
 3            Q.      Do you have any knowledge as to
 4  whether or not a proposed rechallenge study was
 5  thought about or turned down or scrapped?
 6            MR. MYERS:  Thought about by?
 7            MS. ZETTLER:  People at Lilly.
 8            A.      Again, I'm aware of discussions
 9  that seem to have taken place about rechallenge
10  studies, but not being part of the specific
11  discussions I don't remember the pros and cons
12  and reasons for and against and everything else.
13             (PLAINTIFFS' EXHIBIT NO. 1 WAS
14              MARKED FOR IDENTIFICATION AND
15              RECEIVED IN EVIDENCE.)
16            Q.      Have you had a chance to review
17  Exhibit Number 1, Doctor?
18            A.      I have.
19            Q.      Does this refresh your
20  recollection with regards to a rechallenge
21  protocol that was performed by Lilly regarding
22  Fluoxetine and suicidality?
23            A.      This refreshes my memory about
24  this particular memo.

                                                 Page 138

 1            Q.      Okay.  What is -- this memo was
 2  written by you, wasn't it?
 3            A.      This memo was written by me,
 4  that's right.
 5            Q.      Did you attend the meeting with
 6  the FDA discussing a Fluoxetine rechallenge
 7  protocol?
 8            A.      I attended this meeting, yes.
 9            Q.      Tell us about the Fluoxetine
10  rechallenge protocol?  What was the purpose of
11  the protocol?
12            A.      I remember that I attended a
13  meeting and I remember I was asked to write a
14  summary of the meeting which is what this is.
15  But other than what's in the memo, I cannot
16  really address whether or not the specific
17  protocol was further developed or carried out or
18  what because I wasn't involved in that.
19            Q.      Okay.  At the beginning of the
20  memo you say at the FDA meeting Lilly agreed to
21  do the following projects:  One, proceed with the
22  rechallenge study.  Tell me about the particulars
23  of the rechallenge study, what was the objective
24  of the study?

                                                 Page 139

 1            A.      Well, again, getting back to
 2  what I said, I summarized the meeting although
 3  I'm not -- I wasn't the one who was designing any
 4  particular protocol.
 5            Q.      Okay.  From reading this
 6  memorandum, can you recall what the objective of
 7  the study was?
 8            A.      I would only be guessing if I
 9  said what the specific objectives were.  However,
10  if I recollect, I remember discussions that took
11  place afterwards that there were ethical issues
12  in doing such a study.
13            Q.      Let's start with my original
14  question.  Can you tell us generally, from this
15  memorandum, what the objective of the study was?
16            A.      Not from this memorandum.
17            Q.      The study had something to do
18  with suicidality; correct?
19            A.      I believe that's right.
20            Q.      Okay.  What ethical problems
21  would be entailed in conducting a rechallenge
22  Fluoxetine study on the issue of suicidality?
23            A.      It seems to me, at least what I
24  seem to recall from discussion is, a primary

                                                 Page 140

 1  outcome of suicide, looking for that seemed to be
 2  a problem.
 3            Q.      Why?
 4            A.      Because -- obviously because of
 5  the outcome.  The issues were how would you do
 6  such a study safely and monitor patients.
 7            Q.      In other words, it was a
 8  problem of putting a patient at risk of
 9  committing suicide?
10            A.      These are all vague
11  recollections of the discussions that took place.
12  I remember this meeting and I remember
13  summarizing this, but I don't have and I wasn't
14  involved in any design of a rechallenge study.
15  Vague recollections of discussions that took
16  place were about the ethics of such a study, and
17  I guess not having been involved in more detail
18  of it, I can't give you more specifics of what
19  was said.
20            MS. ZETTLER:  Can you read that back?
21             (THE COURT REPORTER READ BACK THE
22              REQUESTED TESTIMONY.)
23            Q.      What outcome were you talking
24  about, Doctor?

                                                 Page 141

 1            A.      Suicide, suicidality.
 2            Q.      Suicidality or actual
 3  accomplished suicide?
 4            A.      Again, that would tie into what
 5  the objectives of the study were, and I can't
 6  remember the specifics.
 7            Q.      Do you remember the risk of
 8  somebody becoming suicidalal while on a
 9  rechallenge on Fluoxetine being a concern during
10  this meeting?
11            A.      I don't recall that being a
12  concern during this meeting.
13            Q.      Were any ethical considerations
14  discussed at this meeting on May 13th, 1991?
15            MR. MYERS:  Other than what he's
16  already told you?
17            MS. ZETTLER:  From his recollection.
18  He says he remembers the meeting, he was there.
19            A.      None others that I recall just
20  from looking at the memo.
21            Q.      Does it seem to you, Doctor,
22  that the potential obvious outcome as you stated
23  it would be something that would be apparent to
24  the people that were at this May 13th, 1991

                                                 Page 142

 1  meeting?
 2            MR. MYERS:  Before he answers, let me
 3  object to the form as to what was apparent to
 4  persons at the meeting other than him because
 5  that would call upon him to speculate as to what
 6  was apparent to them.
 7            A.      This summary apparently
 8  summarizes my impression of the discussion that
 9  took place, I don't know how to answer your
10  question any better.
11            Q.      What I'm asking you is these
12  people here that attended this or the people that
13  attended this FDA meeting, wouldn't that outcome
14  be obvious to them as it is to you?
15            MR. MYERS:  Before he answers, let me
16  object to the form.  I don't know that he's
17  testified as to who was at the meeting yet.
18            A.      I was actually just going to
19  say that I didn't list who was at the meeting,
20  and thus I don't recall if the people addressed
21  on this list were at the meeting.
22            Q.      Obviously there were people
23  from the FDA at the meeting; correct?
24            A.      Yes.

                                                 Page 143

 1            Q.      And there were people from
 2  Lilly at the meeting; correct?
 3            A.      Yes.
 4            Q.      And if you look at the second
 5  page of your memo, the second to the last
 6  paragraph, you say Dr. Leber mentions.  Dr Leber
 7  is Dr. Paul Leber?
 8            A.      Yes.
 9            Q.      And he was the director of
10  neuropsychopharmacology at the FDA?
11            A.      I don't recall his specific
12  title at the time, I think that's his title now.
13            Q.      Okay.  Do you recall that it
14  would be apparent to Dr. Leber at the time of
15  this meeting on May 13, 1991, that one of the
16  obvious outcomes of doing a rechallenge study
17  with suicidality is that somebody may become
18  suicidal on the study?
19            MR. MYERS:  Object to the form again,
20  you're asking him to speculate as to what would
21  be apparent to Dr. Leber, that's not within his
22  personal knowledge.
23            A.      I can't do that, I can't
24  speculate on that.

                                                 Page 144

 1            Q.      It was obvious to you that that
 2  was one of the possible outcomes; correct?
 3            A.      Again, not being involved in
 4  the design of the study and what took place,
 5  rechallenge study, that was, I believe, one of
 6  the objectives being discussed, was to look at
 7  rechallenge of suicidality.
 8            Q.      If you weren't involved in
 9  this, why were you at this meeting?
10            MR. MYERS:  Objection to the form, he
11  didn't say he wasn't involved in it at all, he
12  told you what the extent of his involvement was.
13            Q.      You can answer my question.
14            A.      You know, I don't recall the
15  specific objectives of this meeting between Lilly
16  and the FDA, although this memo summarizes the
17  discussion or at least part of the discussion
18  that took place.
19            Q.      Okay.  I object to this answer
20  as being nonresponsive.  Please answer my
21  question.  If you weren't involved in the
22  development of protocol, why were you at this
23  meeting?
24            MR. MYERS:  Wait a minute, let me

                                                 Page 145

 1  object to the form.  The question you asked him
 2  one question ago was why did you write the memo,
 3  not why were you at the meeting.  So what is the
 4  question?
 5            MS. ZETTLER:  The question I asked
 6  before is why was he at the meeting if he wasn't
 7  involved in the protocol.
 8            MR. MYERS:  No, ma'am, you asked him
 9  why he wrote the memo.
10            MS. ZETTLER:  Okay, Larry, it's a new
11  question.
12            MR. MYERS:  What is the question?
13            Q.      If you weren't involved in
14  writing the protocol, why were you at this
15  meeting?
16            A.      Again, that would be dependent
17  on the specific objectives of the meeting.
18            Q.      You can't tell from this
19  memorandum what the specific objectives of the
20  meetings were?
21            A.      I didn't outline what the
22  objectives of the meeting were in this memo.  I
23  don't even know if this is a formal meeting
24  minute summary.

                                                 Page 146

 1            Q.      Do you have any reason to
 2  believe that you did not write this?
 3            A.      No, I know I wrote this.
 4            Q.      And at the top you say FDA
 5  meeting to discuss Fluoxetine rechallenge
 6  protocol, comma, May 13th, 1991; correct?
 7            A.      Uh-huh.
 8            Q.      So it looks like the topic of
 9  the meeting was discussing the Fluoxetine
10  rechallenge protocol; correct?
11            A.      Per this topic, that's what it
12  says, but there may have been a lot of agenda
13  items for the meeting which would be good to see
14  formal minutes to see what other things were --
15            Q.      This doesn't say that, does it,
16  it says FDA meeting to discuss Fluoxetine
17  rechallenge protocol.
18            MR. MYERS:  Object, he's answered that
19  already, he said that's what it says.
20            Q.      That's what it says, right,
21  Doctor?
22            A.      That's what it says, and you're
23  asking why I was at the meeting, and I expressed
24  that it would be helpful to know the full

                                                 Page 147

 1  objectives of the meeting.
 2            Q.      You have no recollection
 3  whatsoever why you were at that meeting?
 4            MR. MYERS:  Object to the form, that's
 5  not what he said.  He hasn't said he has no
 6  recollection of why --
 7            Q.      Okay.  Do you have any
 8  independent recollection without the formal
 9  agenda -- formal meeting minutes, as to why you
10  were at that meeting?
11            A.      Well, one of the things I had
12  been involved in, which my best guess is why I
13  was there, was the discussion of a modified scale
14  for suicidal ideation revised for use in trials,
15  and I was involved somewhat with discussions in a
16  revised modified scale for suicidal ideation.
17            Q.      And this is the MSSIR that's
18  talked about in paragraph number two?
19            A.      That's correct.
20            Q.      What was your involvement with
21  the MSSIR?
22            A.      At the time, we were talking
23  about ways to try to measure suicidal ideation,
24  different ways to measure suicidal ideation above

                                                 Page 148

 1  and beyond ways that had been done, and we looked
 2  at different instruments that existed, and this
 3  was one we hit upon as an additional possible
 4  measurement tool.
 5            Q.      Okay.  When you say other
 6  measures of suicidality, you're talking about the
 7  Hamilton depression rating scale; correct?
 8            A.      Right.
 9            Q.      And is there some reason you
10  were going to use the MSSIR in a rechallenge
11  protocol as opposed to using the Hamilton
12  depression rating scale?
13            MR. MYERS:  Before he answers, let me
14  object to the form.  I don't think he said they
15  were going to use one instead of the other, he
16  just said they were looking at additional scales.
17            MR. SMITH:  Larry, let her ask her
18  questions.
19            MR. MYERS:  I'm just objecting to the
20  form, Mr. Smith.
21            A.      The -- this was one possibility
22  to be used in addition to ways that had been
23  done, that's correct.
24            Q.      You were considering using the

                                                 Page 149

 1  MSSIR in addition to the Hamilton depression
 2  rating?
 3            A.      It was one option being
 4  explored, that's right.
 5            Q.      What were some of the other
 6  options?
 7            A.      This was the primary one that I
 8  remember being involved in the discussions.
 9            Q.      Do you remember any others?
10            A.      Gee, there were others
11  described and discussed by psychiatrists, but I
12  don't recall them.
13            Q.      Which psychiatrists?
14            A.      The Lilly psychiatrists.
15            Q.      Heiligenstein, Beasley and
16  Wheadon?
17            A.      Right.
18            Q.      Any others?
19            A.      Not that I recall.
20            Q.      What did you mean under number
21  one, looks like bullet two -- or bullet one, it
22  says we need to collect data to characterize the
23  patients who are both enrolled and not enrolled
24  in this study?

                                                 Page 150

 1            A.      That's not very clear, the
 2  thought wasn't very well developed in that one
 3  bullet point.  I honestly cannot reconstruct what
 4  the thought process was on that.
 5            Q.      Why would you have patients
 6  involved in a study who were not enrolled in the
 7  study?
 8            A.      As I say, it's not very clearly
 9  written so I don't recall the thought.
10            Q.      Was a portion of this
11  rechallenge study to be a retrospective analysis
12  of clinical trial data?
13            A.      I don't believe so.
14            Q.      What patient population did you
15  intend on drawing upon for the rechallenge study?
16            A.      Again, not being involved in
17  designing the rechallenge study, I cannot say.
18            Q.      At what point in the
19  development was this protocol at when you had
20  this meeting on May 13th, 1991?
21            A.      I believe I recall seeing
22  preliminary drafts of one.
23            Q.      Okay.  From reading those
24  preliminary drafts, do you have a recollection as

                                                 Page 151

 1  to what the objective of the study was?
 2            A.      No.
 3            Q.      On the third bullet point,
 4  under number one, you say we agree to have a
 5  rechallenge protocol ready to go by September
 6  1st, 1991 and to provide data after the first
 7  quarter which would provide information on six
 8  months of experience.  What does that mean?
 9            A.      Well, it apparently outlines a
10  time line, although based on what was written,
11  there aren't more clearly defined, you know,
12  description of what was to take place.
13            Q.      Do you have an understanding of
14  what the term pilot study means?
15            A.      I believe I do.
16            Q.      What is a pilot study?
17            A.      A pilot study is a small scale
18  study conducted to assess the feasibility of
19  doing a larger scale trial of a similar design,
20  and to assure that the methods of such a study
21  are as well developed as they can be.  The pilot
22  study allows one to make revisions to the study
23  design and revisions to the data collection
24  elements so that the large scale study would be

                                                 Page 152

 1  feasible, practical and basically doable.
 2            Q.      Was a pilot rechallenge study
 3  ever done on Fluoxetine and suicidality?
 4            A.      None that I'm aware of.
 5            Q.      And what you're referring to in
 6  the third bullet line down here, are you
 7  referring to a pilot study?
 8            A.      I do not know that.
 9            Q.      Pardon?
10            A.      It's not clear from what's
11  written, so I do not know that.
12            Q.      To your knowledge, was this
13  rechallenge protocol ever performed?
14            A.      Not that I am aware of.
15            Q.      Do you know why?
16            A.      No.
17            Q.      Who would know why?
18            A.      Probably one of the
19  psychiatrists.
20            Q.      The three that we talked about
21  earlier?
22            A.      Yes.
23            Q.      Beasley, Heiligenstein and
24  Wheadon?

                                                 Page 153

 1            A.      Yes.
 2            Q.      How about some of these other
 3  people listed up here, like W.L. Thompson, is he
 4  a doctor, medical doctor?
 5            A.      W.L. Thompson is a medical
 6  doctor, yes.
 7            Q.      Is he a psychiatrist?
 8            A.      No.
 9            Q.      How about A.J. Weinstein, is he
10  a psychiatrist?
11            A.      He is not a psychiatrist that I
12  am aware of.
13            Q.      Is he a neurologist?
14            A.      No.
15            Q.      What area of medicine does Dr.
16  Thompson specialize in?
17            A.      Well, I can't really address
18  all his areas of specialization.
19            Q.      Do you know if he's Board
20  certified in any area?
21            A.      I believe he is.
22            Q.      What area?
23            A.      That, I cannot address.
24            Q.      You cannot address it because

                                                 Page 154

 1  you won't or you don't know?
 2            A.      Because I don't know.  My
 3  presumption is it's critical care medicine, but
 4  we would have to check on that.
 5            Q.      Any other psychiatrists on this
 6  list?
 7            A.      Wheadon, Beasley, and I believe
 8  that's it.
 9            Q.      How about Dr. Zerbe?
10            A.      No.
11            Q.      In the second paragraph, number
12  two, says incorporate the modified scale for
13  suicidal ideation revised in ongoing and planned
14  U.S. and UK clinical trials.  Do you know if that
15  was in fact ever done?
16            A.      I was involved in the initial
17  discussions on use of the MSSIR, in fact even
18  talking to outside consultants about it.  But I
19  do not know if it ever proceeded because my
20  involvement was limited in that regard.
21            Q.      You were talking outside
22  consultants, but you don't know if they ever
23  incorporated the MSSI into any of these other two
24  trials?

                                                 Page 155

 1            A.      That's right.
 2            Q.      Who were the other consultants
 3  you were talking to?
 4            A.      There was one from Brown
 5  University, I cannot remember if his name Ivan is
 6  his first name or last name, but that's the name
 7  I remember.
 8            Q.      Anybody else?
 9            A.      No.
10            Q.      Who developed the MSSIR?
11            A.      I don't know.
12            Q.      Who would know whether or not
13  the MSSIR was incorporated into the planned and
14  ongoing U.S. and UK clinical trials?
15            A.      Presumably one of the
16  psychiatrists.
17            Q.      Under number three on the
18  second page, you state in the second full
19  sentence:  In particularly asked if Dr. Ticher
20  had reviewed this scale or if we could share it
21  with Dr. John Cole, the second author.
22            A.      Yes.
23            Q.      To your knowledge, did Dr.
24  Teicher or Dr. Cole ever review that scale?

                                                 Page 156

 1            A.      I'm unaware if they did.
 2            Q.      Who is Barbara Stanwick?
 3            A.      Honestly I don't recall who
 4  Barbara Stanwick is, not at this time.
 5  Presumably a psychiatrist, but I don't know.
 6            Q.      Who to your knowledge would
 7  have primary responsibility for developing the
 8  protocol for the rechallenge study?
 9            A.      At that time it was probably
10  Charles Beasley, although it could have been any
11  one of the three psychiatrists.
12            Q.      Why is it that you weren't
13  involved in developing the protocol, if you know?
14            A.      It was probably a question -- I
15  mean I don't recall the exact answer to that,
16  although it was probably a question of work load
17  distribution and also expertise in the area.
18            Q.      What do you mean under the
19  third bullet point under number three where it
20  says the FDA did not have a problem if we gave
21  the MSSIR to other companies to use in their
22  clinical trials?
23            A.      Well, at the time it
24  undoubtedly had a meaning, but I don't recall

                                                 Page 157

 1  what that meaning is now.
 2            Q.      What do you mean other
 3  companies, are you talking other companies who
 4  are doing clinical trials on Fluoxetine?
 5            A.      That's a possible answer, or
 6  just other trials on depression.
 7            Q.      Depression in general or
 8  depression as it relates to other
 9  anti-depressants?
10            A.      I don't know.
11            Q.      To your knowledge did Lilly
12  ever work with any outside companies on studies
13  related totally to depression?
14            MR. MYERS:  Object to the form, what do
15  you mean by outside companies?
16            MS. ZETTLER:  Other companies, let's
17  use that.
18            A.      I'm unaware if they have, if
19  Lilly has.
20            Q.      Could other companies mean
21  other companies related to Lilly such as other
22  divisions or affiliates?
23            A.      I guess anything is possible,
24  you know, any answer like that is possible.

                                                 Page 158

 1            Q.      The fourth project listed in
 2  the memo is descriptive study of patients
 3  reported to develop intensive violent suicidal
 4  thoughts.  Do you know if that study was ever
 5  done?
 6            A.      Not that I'm aware of.
 7            Q.      Was there a particular patient
 8  population that you were going to look at in this
 9  study?
10            A.      Well, short of having the
11  details captured in the text here, I can't
12  recall.
13            Q.      Why did you write this memo?
14            MR. MYERS:  I object to the form, he's
15  already told you that, he's already answered that
16  question.
17            MS. ZETTLER:  I don't believe he has.
18            A.      Yes, I wrote it as a summary of
19  the meeting, of the discussion that took place at
20  the meeting.
21            Q.      Why did you have to write this
22  if there were detailed minutes of the meeting?
23            MR. MYERS:  I object to the form, he
24  didn't say there were detailed minutes.

                                                 Page 159

 1            MS. ZETTLER:  Yes, he did.
 2            A.      I don't recall if I said
 3  detailed or not, but -- that's a good question.
 4  I can't recall if I was specifically asked to
 5  write them.
 6            Q.      Well, you wrote it and you sent
 7  it to a number of people, didn't you?
 8            A.      That's correct.
 9            Q.      Are you in the habit of writing
10  things on your own without being asked to and
11  sending it out to a number of different people?
12            A.      I don't recall for this
13  specific memo.
14            Q.      How about other memos, is that
15  your habit?
16            MR. MYERS:  Is what his habit?
17            MS. ZETTLER:  To write a memorandum to,
18  looks like, ten or twelve-odd people regarding a
19  subject matter when he hasn't been asked to?
20            A.      I do what I believe is
21  necessary with my job.
22            Q.      Do you believe that this was
23  necessary if somebody else was writing up the
24  meeting minutes?

                                                 Page 160

 1            A.      At the time that this was
 2  written, my presumption is I was unaware of
 3  anyone writing the meeting minutes.
 4            Q.      So you wrote this strictly from
 5  your own memory?
 6            A.      This particular memo, yes.
 7            Q.      Are you aware whether or not
 8  anybody did write up formal meeting minutes for
 9  this meeting?
10            A.      My presumption is it's
11  possible, they could have been written as formal
12  meeting minutes.
13            Q.      It's possible that they
14  couldn't have also, right?
15            A.      Right, but my presumption is
16  they probably were.
17            Q.      You've never seen the formal
18  meeting minutes for this meeting?
19            A.      I was not always a recipient of
20  formal meeting minutes.
21            MR. SMITH:  That's not what she asked
22  you, she said you've not seen any other formal
23  meetings minutes.
24            A.      I don't recall any formal

                                                 Page 161

 1  meetings minutes from this meeting.
 2            Q.      If formal meeting minutes were
 3  written up, would they be contained in your file?
 4            MR. MYERS:  Object to the form only
 5  because --
 6            MS. ZETTLER:  I think it's simple and
 7  straight forward.
 8            MR. MYERS:  No, it isn't.  What if the
 9  FDA wrote the meeting minutes, since the FDA was
10  the other party at the meeting, for instance.
11            A.      I'm unaware if so.
12            Q.      You're unaware of what?
13            A.      What I thought your question
14  was.
15            Q.      My question was:  If there were
16  formal meeting minutes written, would they be
17  contained in your file?
18            A.      I'm sorry.  If I received a
19  copy, yes, they would be in my file.
20            Q.      Is there any reason why you
21  would not have received a copy?
22            A.      As I said, I did not always
23  receive all the meeting minutes.
24            Q.      In what situations would you

                                                 Page 162

 1  not receive meeting minutes?
 2            A.      Well, there are always lots of
 3  activities ongoing, some of which I was involved
 4  in, others I wasn't involved in, and clearly it's
 5  an administrative issue to try to get minutes out
 6  to everybody that either has a need to know or
 7  should know.  So I would be on the receiving end
 8  of those things which I would be specifically
 9  working on, although not all the time would I get
10  a copy of such minutes.
11            Q.      You were involved in this
12  meeting, weren't you?
13            A.      Yes.
14            Q.      And you felt it necessary to
15  write up a summary of what you believe occurred
16  at the meeting, didn't you?
17            A.      I did.
18            Q.      But you wouldn't be involved
19  enough to get a copy of the meeting minutes if
20  they were written up?
21            A.      Again, if they were and I did
22  get a copy and I had them in my file, then you
23  should have a copy in your file, I presume.
24            MS. ZETTLER:  I think that's a pretty

                                                 Page 163

 1  strong presumption.
 2            Q.      Under number four it says that
 3  Dr. Stadel suggested a pilot study on patients
 4  who developed intense violent suicidal thoughts.
 5  To your knowledge was that pilot study ever done?
 6            A.      Again, not that I'm aware of.
 7            Q.      Who would know that?
 8            A.      Once again, I would need to
 9  defer to one of the psychiatrists.
10            Q.      What do you mean in this last
11  sentence under number four, the main concern of
12  Dr. Leber is that he failed to find the syndrome
13  in this descriptive study, then what have we
14  shown?
15            A.      My presumption is -- again,
16  without more text to describe what is going on by
17  this one sentence, is that if you don't find this
18  syndrome of intensive violent suicidal thoughts,
19  then you don't have a descriptive study,
20  obviously, because that's what you're looking
21  for.
22            Q.      If you don't find a syndrome in
23  who?
24            A.      It's not detailed in this

                                                 Page 164

 1  summary.
 2            Q.      Severely depressed patients?
 3            A.      The presumption is that's the
 4  population, although it's not detailed in this
 5  memo.
 6            Q.      Garden variety depressed
 7  patients?
 8            MR. MYERS:  I object to the form, I
 9  don't know if that's a medical or scientific
10  term.
11            MR. SMITH:  Apparently being used by
12  your employees.
13            MR. MYERS:  What is?
14            MS. ZETTLER:  Garden variety patients.
15            MR. MYERS:  Direct him to that, and see
16  if that's what he means.
17            Q.      In the next full paragraph, Dr.
18  Leber mentioned that it may be worthwhile to
19  determine what the risk, paren, incidence, close
20  paren, is of the development of these symptoms in
21  garden variety patients treated for the first
22  time with Fluoxetine versus other agents.  What's
23  a garden variety patient?
24            A.      That's a good question, one

                                                 Page 165

 1  that I don't know the answer to.
 2            Q.      You wrote that, didn't you?
 3            A.      I did, I wrote it two years
 4  ago.
 5            Q.      Did somebody tell you to answer
 6  questions based on your lack of memory in these
 7  depositions, Doctor?
 8            A.      Nobody has.
 9            Q.      Did anybody suggest to you that
10  that would be appropriate?
11            A.      Nobody has.
12            Q.      Why is it that you don't
13  remember something like a rechallenge study on
14  suicidality in patients with Fluoxetine?
15            MR. MYERS:  Before he answers, let me
16  object to the form.  He has testified about it to
17  the extent he does recall it, so your
18  characterization that he does not recall it is
19  inaccurate.
20            Q.      Doctor, did anybody ever tell
21  you in response to questions to listen to your
22  attorney's objections --
23            MR. MYERS:  Don't answer that question
24  as to any discussion you had with me or any other

                                                 Page 166

 1  lawyer for Lilly, don't answer that.  Ask another
 2  question.
 3            Q.      Why is it that you don't
 4  remember details about the rechallenge protocol
 5  when you were obviously involved?
 6            A.      Well, I answered as well as I
 7  can answer based on a review of this memo and
 8  previous discussions that we had.
 9            Q.      Let's talk about central
10  nervous system disorders.  Were you involved in
11  any studies on central nervous system disorders
12  with regards to Fluoxetine?
13            A.      Can you be more specific on
14  central nervous system disorders?
15            Q.      Movement disorders, were you
16  involved in study of movement disorders as they
17  related to the use of Fluoxetine?
18            A.      Yes.
19            Q.      Which studies?
20            A.      We did a routine review of the
21  movement disorder adverse events?
22            Q.      A routine review?
23            A.      Yes.
24            Q.      Why was a routine review done?

                                                 Page 167

 1            A.      It's part of our ongoing
 2  surveillance and maintenance and evaluation of
 3  different adverse event terms that we believe
 4  should be investigated further.
 5            Q.      Earlier you said you did a
 6  routine review, now you're saying that events
 7  that should be investigated further.  Is that one
 8  and the same or is there a difference?
 9            MR. MYERS:  I object to the form, I
10  think earlier he talked about both before the
11  lunch break.
12            A.      All adverse events are
13  evaluated, but upon evaluation there are some
14  that may require further investigation, either
15  due to the nature of the description of the event
16  or an increase in the event or for a number of
17  reasons.
18            Q.      Tell me what a routine review
19  entails?
20            A.      A routine review involves
21  evaluation of all event terms, aggregations of
22  event terms, and if further detailed
23  investigation is necessary, then it's taken --
24  undertaken.

                                                 Page 168

 1            Q.      What is aggregation of event
 2  terms?
 3            A.      Besides looking at each adverse
 4  event term or each adverse event report
 5  individually, they're clustered with other
 6  adverse event terms that are similar or the same,
 7  to see if there are any specific trends or
 8  descriptive data that indicates a hypothesis.
 9            Q.      So in other words, grouping
10  under specific body systems?
11            A.      That's part of it, sure.
12            Q.      Tell me the criteria that
13  indicate that you need to review an adverse event
14  or aggregation of adverse events in greater
15  detail?
16            A.      Each investigation differed,
17  but it's usually tied into the specific disease
18  process or event that's ongoing.
19            Q.      Give me an example?
20            A.      For example, in movement
21  disorders, we wanted to look further on the issue
22  of dyskinesia and we wanted to make sure that we
23  had as broad a capture of all dyskinesia cases as
24  we could find, hence we clustered a large number

                                                 Page 169

 1  of movement disorders, a number of different
 2  terms, to see if we could have complete data
 3  captured.  That's an example.
 4            Q.      Why did you want to look at
 5  dyskinesia?
 6            A.      I don't recall exactly what
 7  triggered dyskinesia as something we wanted to
 8  look at further, but the point is we undertook a
 9  more detailed analysis of it.
10            Q.      Was the number of adverse
11  events related to dyskinesia that were reported
12  trigger the further analysis of dyskinesia?
13            A.      Well, actually I believe the
14  dyskinesia example was one where it was an
15  ongoing project that was evaluated prior to my
16  involvement in it.  And it was a continuation of
17  that evaluation to follow up on all the cases to
18  see the resolution of the dyskinesia, and that
19  was part of it.
20            Q.      What do you do in follow-up?
21            A.      You contact the physicians to
22  see -- to get more medical information about each
23  of the patient reports.
24            Q.      Did you contact the patients

                                                 Page 170

 1  themselves?
 2            A.      No.
 3            Q.      Why not?
 4            A.      Because our approach is to go
 5  through the physician to get detailed -- as
 6  detailed medical information as we can.
 7            Q.      Why is your approach to go
 8  through the physician as opposed to contacting
 9  the patient?
10            A.      Well, first of all, one can get
11  the most detailed medical information, accurate
12  medical information, from a physician.
13            Q.      Are all physicians qualified to
14  render opinions on dyskinesia?
15            MR. MYERS:  I object to the form,
16  that's not what he said.
17            MS. ZETTLER:  That's my question, I'm
18  asking him.
19            A.      Whether or not all physicians
20  are qualified to render an opinion on dyskinesia,
21  the reporting physician and the physician that
22  takes care of the patient is certainly qualified
23  to comment on the patient's medical history,
24  medications they are taking, outcomes.  Thus we

                                                 Page 171

 1  contact the physicians.
 2             (PLAINTIFFS' EXHIBIT NO. 2 WAS
 3              MARKED FOR IDENTIFICATION AND
 4              RECEIVED IN EVIDENCE.)
 5            Q.      Have you had at chance to
 6  review Exhibit 2, Doctor?
 7            A.      Yes.
 8            Q.      Do you recognize Exhibit 2?
 9            A.      I don't recall it specifically,
10  but I do know I received it based upon the
11  address list.
12            Q.      Whose handwriting is this on
13  the corrections area?
14            A.      I was trying to figure that
15  out, in fact I was hoping that there would be a
16  name at the end, but there wasn't.  I presume
17  it's a note from Katie Copley-Merriman, although
18  this does not look like her handwriting.
19            Q.      Okay.  Was Lilly studying
20  tardive dyskinesia as it related to suicidal
21  ideation?
22            A.      No.
23            Q.      What does this person mean down
24  here where it says comments reviewed for

                                                 Page 172

 1  reference to suicide acts or ideation only?
 2            MR. MYERS:  Before he answers, let me
 3  object to the form of him commenting or
 4  interpreting what some writer other than he
 5  meant.
 6            A.      My presumption is that the
 7  comment section of the case report forms, that
 8  that is the data collection elements in the
 9  clinical trials, were reviewed with reference to
10  suicidal acts or ideation and not tardive
11  dyskinesia.
12            Q.      Are you familiar with the
13  disease called akathesia or a syndrome called
14  akathesia?
15            A.      I'm familiar with the term.
16            Q.      What is akathesia?
17            A.      Perceived restlessness.
18            Q.      Perceived by whom?
19            A.      The patient.
20            Q.      What is tardive dyskinesia?
21            A.      It's a chronic involuntary
22  movement disorder seen in patients exposed to
23  neuroleptic drugs or that is drugs used for the
24  treatment of schizophrenia.

                                                 Page 173

 1            Q.      Is Prozac considered a
 2  neuroleptic drug?
 3            A.      No.
 4            Q.      Why not?
 5            A.      Actually, if it is, I'm unaware
 6  of it being referred to as one.  Prozac is
 7  considered a selective seritonin uptake
 8  inhibitor, whereas neuroleptic drugs impact the
 9  dopamine system or dopamine receptors.
10            Q.      And there are various drugs
11  that are considered neurolectics that have
12  different actions than the dopamine structures,
13  right?
14            A.      There are different neuroleptic
15  drugs that have similar mechanism of action on
16  the dopamine receptors.
17            Q.      So calling a drug a neuroleptic
18  is like classifying Prozac as an anti-depressant,
19  isn't it, it's a much broader category?
20            A.      That's probably correct,
21  although it would be helpful to review a textbook
22  of pharmacology to make sure all of our
23  definitions are correct.
24            Q.      Akathesia is a condition that

                                                 Page 174

 1  has been related to the use of neurolectics,
 2  isn't it?
 3            A.      It's one of the events reported
 4  in association with neuroleptic use, yes.
 5            Q.      And suicidal ideation has been
 6  related to both akathesia and tardive dyskinesia,
 7  haven't they?
 8            A.      Repeat your question?
 9            Q.      Sure.  I'll break it down.
10  Suicidal ideation has been related to the
11  condition of akathesia; correct?
12            A.      I'm unaware of it being
13  associated with -- suicidal ideation being
14  associated with akathesia.
15            Q.      Are you aware of tardive
16  dyskinesia being associated with suicidal
17  ideation?
18            A.      I'm unaware of data supporting
19  that.
20            Q.      Are you aware that data has
21  been published that talks about an association
22  between tardive dyskinesia and suicidal ideation?
23            A.      Correct, I'm unaware of any
24  data published supporting that premise.

                                                 Page 175

 1            Q.      Are you aware of any data
 2  published supporting the premise that akathesia
 3  is related to suicidal ideation?
 4            A.      I seem to recall a few case
 5  reports, I believe, in the literature, but that's
 6  the best recollection I have.
 7            Q.      Did you work with some
 8  consultants on the issue of tardive dyskinesia
 9  and movement disorders related to the use of
10  Fluoxetine; correct, outside consultants?
11            A.      We worked with outside
12  consultants regarding movement disorders in
13  relation to Fluoxetine.
14            Q.      Movement disorders in general
15  or any one in particular?
16            A.      We looked broadly at movement
17  disorders.
18            Q.      Tell me who those consultants
19  were?
20            A.      Drs.  Harold Clemens and Bill
21  Glazier.
22            Q.      Anybody else?
23            A.      Those are the two in which I
24  was involved.

                                                 Page 176

 1            Q.      Any other names that you can
 2  remember whether or not you were involved with
 3  them directly?
 4            A.      If there were others involved
 5  in looking at movement disorders outside the time
 6  I worked on it, I'm unaware of it.
 7            Q.      Have you ever heard the name
 8  Jan Fawcett, M.D.?
 9            A.      Yes.
10            Q.      Do you know Dr. Fawcett?
11            A.      I do not know him personally, I
12  only know of him.
13            Q.      What is it that you know about
14  him?
15            A.      I believe he's a psychiatrist,
16  I know he's published extensively in the area of
17  depression.
18            Q.      To your knowledge, has Dr.
19  Fawcett ever performed a clinical trial on
20  Fluoxetine?
21            A.      I don't know if he has or he
22  hasn't.
23            Q.      To your knowledge has he ever
24  consulted with Lilly on the issue of Fluoxetine

                                                 Page 177

 1  as it relates to suicide or suicidal ideation?
 2            A.      I believe he has.
 3            Q.      In what capacity?
 4            A.      I'm not being flippant, but I
 5  believe as a consultant on depression and
 6  suicidality.
 7            Q.      Depression as it relates to
 8  suicidality?
 9            A.      I believe it was on just what I
10  said, on depression and suicidality.
11            Q.      I need you to be a little more
12  specific, Doctor.  Do you mean the incident rate
13  of depression or suicidality and the disease
14  process of depression or the incidence of suicide
15  with regards to Fluoxetine in patients who are
16  depressed?
17            MR. MYERS:  Are those the only two
18  alternatives he has?
19            MS. ZETTLER:  So far.
20            A.      I believe he was involved in
21  the discussion of the disease depression, its
22  incidence, the outcomes.  Anymore specific
23  involvement, such as on the issue of specific
24  treatments and the outcomes of depression, I do

                                                 Page 178

 1  not know to what capacity he was involved as a
 2  consultant.
 3            Q.      Did he consult in any way on
 4  the incidence of depression on patients on
 5  Fluoxetine?
 6            MR. MYERS:  Wait a minute, the
 7  incidence of depression?
 8            Q.      I'm sorry, suicide.
 9            A.      Can we take a quick
10  five-minutes break?
11            Q.      Sure.  Why don't you answer
12  that question first.
13            A.      Okay, repeat it, please, since
14  we both started to twist words around.
15            Q.      Okay.  To your knowledge did
16  Dr. Fawcett consult on the issue of suicidality
17  and the use of Fluoxetine?
18            A.      I remember Dr. Fawcett being
19  involved in discussions on the disease
20  depression, and I know that Lilly had a number of
21  outside psychiatric consultants consulted on the
22  issue.  Whether or not Dr. Fawcett was asked to
23  specifically address the issue of Fluoxetine and
24  suicidality, I don't know his specific

                                                 Page 179

 1  involvement.
 2            Q.      Okay.
 3             (A SHORT RECESS WAS TAKEN.)
 4            Q.      Is it your understanding that
 5  Lilly investigated the relationship between
 6  movement disorders and the use of Fluoxetine?
 7            A.      Yes.
 8            Q.      What was your involvement in
 9  that investigation?
10            A.      My involvement was to work with
11  one of the psychiatrists to identify all movement
12  disorder terms that we believed would capture any
13  events of dyskinesia, and then to identify two
14  outside experts and ask them to review these
15  reports and give us their evaluation and
16  assessment on categorizing these movement events
17  into different types.  And obviously they were
18  all patients who had been on Fluoxetine.
19            Q.      Okay.  Do you mean categorize
20  them in different types of movement disorders?
21            A.      We told them to focus on
22  dyskinesia or possible dyskinesias.
23            Q.      Did any of your consultants say
24  there was a correlation between the use of

                                                 Page 180

 1  Fluoxetine and dyskinesia?
 2            A.      I don't recall if they
 3  specifically said that, but we were most
 4  interested in their perception of different types
 5  of dyskinesia, tardive versus non-tardive.
 6            Q.      What's the difference between
 7  tardive versus non-tardive dyskinesia?
 8            A.      As I recall, the outside
 9  experts seemed to reference a definition by
10  Schooler and Kane of tardive dyskinesia being the
11  development and persistence of dyskinesia
12  involuntary movements, after three months
13  continuous or accumulative discontinuous use of
14  neuroleptic drugs.
15            Q.      What about dyskinesia?
16            A.      Dyskinesia is involuntary
17  movement disorders.
18            Q.      Is it associated with the
19  length of time that they're exposed to a
20  neuroleptic?
21            A.      Dyskinesia just describes the
22  involuntary movement disorder, tardive dyskinesia
23  incorporates the time frame.
24            Q.      And prolonged exposure to

                                                 Page 181

 1  neurolectics.
 2            A.      Neurolectics, per Schooler and
 3  Kane definition.
 4            Q.      Do you disagree with that
 5  definition?
 6            A.      No, I do not disagree with the
 7  definition.
 8            Q.      What movement -- when you say
 9  you helped with determining movement disorder
10  terms, are you talking about the ELECT adverse
11  event terms?
12            A.      Yes.
13            Q.      What terms did you guys decide
14  were related to movement disorder?
15            A.      Well, we had over a dozen terms
16  identified, I seem to recall.  I couldn't list
17  them all for you, but there were numerous ones,
18  such as tremor, extra-parametal syndrome,
19  dyskinesia.
20            Q.      Dystonia?
21            A.      If that was an ELECT term, yes,
22  that was one of them.
23            Q.      Akathesia?
24            A.      I believe I said that one.

                                                 Page 182

 1  Could have been hypertonia in there and
 2  hypotonia, but I cannot recall with certainty.
 3            Q.      Restlessness?
 4            A.      That may have been one of the
 5  terms, I do not recall specifically.
 6            Q.      Agitation?
 7            A.      I would have to look at our
 8  list again that we use to generate all the terms.
 9            Q.      Who was the psychiatrist you
10  worked with on the tardive dyskinesia issue?
11            A.      Well, the outside consultant
12  psychiatrist was Dr. Glaser.
13            Q.      How about in-house?
14            A.      Charles Beasley.
15            Q.      Other than -- if I
16  mischaracterize your testimony, please let me
17  know, but other than submitting the case reports
18  to the outside consultants, was there anything
19  else done to study the relationship between
20  Fluoxetine and movement disorders?
21            A.      Clearly we spent a lot of time
22  following up with physicians who reported
23  movement events to get more information about the
24  patients and further describing the types of

                                                 Page 183

 1  movement events they reported.
 2            Q.      Were there any cases of
 3  movement disorder that arose during the clinical
 4  trials?
 5            A.      Well, there were reports of
 6  movement disorders during the clinical trials.
 7            Q.      How many reports, if you know?
 8            A.      I do not know.
 9            Q.      Did you take into consideration
10  information from international clinical trials as
11  well as United States clinical trials?
12            A.      I believe the project we
13  undertook in reviewing the spontaneous adverse
14  event data included review of the international
15  reports as well.
16            Q.      Did any of those cases that
17  were submitted to the outside consultants include
18  international clinical trial participants?
19            A.      I don't recall the answer to
20  that.  I'm tempted to say they were just
21  post-marketing events, but I do not recall with
22  certainty.  There may have been more -- they may
23  have included clinical trial reports, but I don't
24  recall specifically.

                                                 Page 184

 1            Q.      How many cases were submitted
 2  to the outside consultants for review?
 3            A.      Well, there were about two
 4  dozen that we wanted them to focus on, but I
 5  think there were more like a total of around two
 6  hundred or so that we submitted in aggregate to
 7  the consultants to review.  And again, that
 8  number is an approximation, I think there's a
 9  wide range of error on that, could be plus or
10  minus a hundred and fifty, I don't recall with
11  exact certainty.
12            Q.      Who decided which of the cases
13  to submit to the outside consultants?
14            A.      Well, we took them all and
15  submitted them to the consultants.
16            Q.      When you say took them all,
17  what do you mean?
18            A.      We defined a time period in
19  which events were reported to us, and for all the
20  identified event terms of movement disorders, we
21  compiled all of those up to the date that we were
22  working on it and sent them to the outside
23  consultants.
24            Q.      You set a date as to when the

                                                 Page 185

 1  adverse events would be submitted from -- in
 2  other words to January 1, 1991 or something like
 3  that?
 4            A.      Whatever date we started
 5  working on it, we would say give us all the event
 6  terms reported up until today.  And clearly, as
 7  we would get more adverse event terms, we would
 8  always evaluate them.  But for purposes of the
 9  outside consultant review, we had to have some
10  limit, but our own internal ongoing review
11  continued.
12            Q.      Do you remember what the
13  cut-off date was?
14            A.      No.
15            Q.      Does July of 1990 sound
16  familiar?
17            A.      Truthfully, no, I don't
18  remember the cut-off date.
19            Q.      Who decided on the cut-off
20  date?
21            A.      Well, it was the date we
22  started working on it, so whatever date that was.
23  And it's hard to reconstruct now, I mean there's
24  a lot involved in doing these types of projects

                                                 Page 186

 1  and it's possible -- now I'm starting to view the
 2  question, it's possible that as we revised terms,
 3  we may have even rerun our data base again to
 4  later dates, but I would need to refresh my
 5  memory and the methods used.
 6            Q.      How many consultants, outside
 7  consultants, worked on the movement disorder
 8  issue?
 9            A.      Two.
10            Q.      Two that you worked directly
11  with or two, period?
12            A.      Two that I worked directly
13  with.
14            Q.      I think earlier you may have
15  testified there may have been others, but you
16  don't remember their names?
17            A.      No, I testified that when I was
18  working on this project there were two that we
19  had identified to work on it with us.  Now
20  outside of the times I worked on this, if there
21  were other consultants used, then I don't know if
22  and who these persons would be.  But I certainly
23  know the two that I worked with.
24            Q.      Was a rechallenge study ever

                                                 Page 187

 1  done with regards to movement disorders and use
 2  of Fluoxetine?
 3            A.      None that I'm aware of.
 4            Q.      Were the results of the
 5  consultant's study of the case reports ever
 6  published?
 7            A.      They wrote summaries, summary
 8  reports for us, which we submitted to the FDA.
 9            Q.      Were the summary results ever
10  published in the medical journal or psychiatric
11  journal?
12            A.      Not that I'm aware of, no.
13            Q.      What's a Prozac safety team?
14            A.      I believe the best way to
15  answer that question is to describe it as a
16  collection of individuals who were identified to
17  work on Prozac safety issues, although it was not
18  necessarily all inclusive.  Certainly everybody
19  that was on the team had other duties, and people
20  who were not necessarily identified for the team
21  certainly worked on safety issues.
22            Q.      Is the safety team set up with
23  regards to other drugs manufactured by Lilly?
24            A.      I suppose it comes down to

                                                 Page 188

 1  definition about who does what, but I suppose one
 2  could argue that the drug epidemiology unit in a
 3  sense is a safety team to monitor and collect
 4  safety data on Lilly products.
 5            Q.      On the other drugs that you
 6  have worked on at Lilly, have you ever been
 7  involved in a formalized safety team established
 8  for a specific drug, other than Prozac?
 9            A.      For other drugs, there was
10  never the volume of reports generated from
11  newspapers and media, and thus a large collection
12  of persons was never needed.  Usually one or two
13  people could do the job.
14            Q.      Were bleeding events generated
15  by the media?
16            A.      Bleeding events was actually a
17  generated question by the FDA based on one
18  patient who had an idiosyncratic response in one
19  of the studies.
20            Q.      So the answer is no, it wasn't
21  generated by media.
22            A.      Right.
23            Q.      How about aplastic anemia, were
24  those reports a result of media on Prozac?

                                                 Page 189

 1            A.      No.
 2            Q.      How about liver dysfunction?
 3            A.      I don't believe so.
 4            Q.      How about pregnancy?
 5            A.      No.
 6            Q.      To your knowledge were any
 7  epidemiological studies done on the incidence of
 8  suicidal ideation or suicide and the use of
 9  Fluoxetine?
10            MR. MYERS:  By?
11            MS. ZETTLER:  By Lilly.
12            A.      Could you repeat the question?
13            Q.      Sure.  To your knowledge were
14  any epidemiological studies done specifically on
15  the issue of suicidality and the use of
16  Fluoxetine?
17            MR. MYERS:  By Lilly?
18            MS. ZETTLER:  By Lilly.
19            A.      One could define the study done
20  by Masica, Kotsanos, Beasley and Potvin,
21  published in the American Journal of Public
22  Health, as an epidemiological study.  One could
23  define ongoing collection analysis of
24  spontaneously reported adverse event data as

                                                 Page 190

 1  epidemiological studies.  So the answer is yes.
 2            Q.      Was the second study that you
 3  just mentioned, was there ever a study like that
 4  done at Lilly?
 5            A.      Maybe I should clarify.  The
 6  ongoing collection of spontaneous adverse event
 7  data and analysis and assessment is an
 8  epidemiological approach to data, and that's
 9  something that goes on for all Lilly products.
10             (PLAINTIFFS' EXHIBIT NO. 3 WAS
11              MARKED FOR IDENTIFICATION AND
12              RECEIVED IN EVIDENCE.)
13            Q.      Have you had a chance to review
14  Exhibit 3, Doctor?
15            A.      Yes.
16            Q.      Did you author this E-mail?
17            A.      It looks like I did, yes.
18            Q.      And do you recognize it?
19            A.      Vaguely, sure.
20            Q.      Are you familiar with the
21  subject matter?
22            A.      Yes.
23            Q.      Okay.  At the bottom of this in
24  the middle of the page it looks like a couple of

                                                 Page 191

 1  columns, one says topic and the other assignment;
 2  correct?
 3            A.      Yes.
 4            Q.      At the bottom of the topic
 5  column it says suicide, and then paren, post-EPI
 6  studies, close paren.
 7            A.      Yes.
 8            Q.      What does EPI studies mean?
 9            A.      Those are proposed epidemiology
10  studies, and that referred to review of
11  epidemiology proposals we received from outside
12  people proposing to do different types of
13  studies.
14            Q.      Can you give me an idea of who
15  proposed doing different types of studies, from
16  outside of Lilly?
17            A.      Well, as a company involved in
18  conducting research, we receive numerous
19  proposals to do numerous types of studies on all
20  of our compounds and for the diseases in which we
21  work, and Fluoxetine depression is no different.
22  At the time that the whole suicidality issue was
23  addressed, individuals that had access to data
24  bases, individuals outside of Lilly would write

                                                 Page 192

 1  proposals to analyze their existing data bases to
 2  evaluate suicidality in patients taking
 3  Fluoxetine versus other agents.
 4            Q.      Did Lilly ever take anybody up
 5  on their offer?
 6            A.      I don't recall ever funding any
 7  of the proposals submitted to us, at least not
 8  during the time I was working on it.
 9            Q.      Why not?
10            A.      Methodological reasons.
11            Q.      Such as?
12            A.      A number of different potential
13  biases that would exist in the study as proposed,
14  and due to the limitations of the existing data
15  bases, that could not be overcome, thus the
16  design had problems that would not be the best
17  approach.
18            Q.      Give me an example of a bias
19  that would render a design inappropriate?
20            A.      Most of the proposals, the ones
21  I remember anyway, wanted to identify cohorts of
22  anti-depressant users and their data base,
23  whether they be health maintenance organization
24  data bases or other types of data bases, like in

                                                 Page 193

 1  a clinic.  They would identify depressed patients
 2  that were on these different treatments and
 3  follow them forward in time and look at the
 4  difference in rates of suicide in these cohorts
 5  of patients and then compare the rates.  However,
 6  because of the complexities of the disease, such
 7  as comorbidities of personality disorders, for
 8  example, patients with personality disorders may
 9  be more at risk of being suicidal.  Or patients
10  who presented with depression and who are
11  actively suicidal may be more likely to get
12  Fluoxetine than a tricyclic because it's
13  perceived to be a safer drug in overdose, then
14  the deck would be stacked against Fluoxetine and
15  could not be analyzed, that bias could not be
16  controlled for because those data were not
17  collected at base line and the cohort received
18  Fluoxetine versus other drugs.
19                    And due to biases such as that,
20  their term selection biases, it would be
21  difficult to interpret the results, the outcomes
22  of those types of studies.
23            Q.      Would you agree that in the
24  general population Prozac is prescribed to people

                                                 Page 194

 1  who have these various disorders you just talked
 2  about, bi-polar disorders, previous suicidal
 3  ideation?
 4            A.      That was another bias,
 5  actually, that we saw, and that is many times
 6  people with these data bases did not have
 7  captured the indication for use.  Sometimes it
 8  wasn't even clear if the patient was depressed,
 9  if they were on those anti-depressant agents, and
10  it would be difficult to look at an outcome for
11  depression if in fact the patient was getting the
12  drug for a reason other than depression.  For
13  example, if you just went in blindly and
14  identified a number of tricyclic users, you may
15  actually find patients who have urinary
16  incontinence to be getting tricyclics and thus
17  not be depressed.  And you have different patient
18  populations and it's very difficult to interpret
19  the results of such a study.
20            MS. ZETTLER:  I move to strike as
21  non-responsive.
22            Q.      Would you agree with me,
23  Doctor, that in the general population patients
24  who are prescribed Prozac suffer from various

                                                 Page 195

 1  disorders other than just depression?
 2            A.      I'm sorry, repeat it one more
 3  time because I want to answer your question.
 4            Q.      Sure.  Would you agree with me
 5  that in the general population, people are
 6  prescribed Prozac for reasons other than
 7  depression?  In other words, bipolar disorder,
 8  obsessive-compulsive disorder, panic attacks,
 9  varying degrees of depression?
10            A.      Although Fluoxetine is
11  indicated for depressed patients, I'm aware that
12  physicians use it for indications other than
13  depression.
14            Q.      So your answer is yes?
15            A.      Yes.
16            Q.      And also, isn't it true that
17  Lilly personnel have themselves published papers
18  with regards to using Fluoxetine for indications
19  other than depression?  In other words papers on
20  using Fluoxetine with obsessive-compulsive
21  disorder, panic attacks, bulimia, obesity, and
22  other syndroms and conditions?
23            A.      Are you saying these are Lilly
24  authors?

                                                 Page 196

 1            Q.      Yes, we can start with Lilly
 2  authors.
 3            A.      Because I'm unaware of any, I
 4  personally am unaware of any.
 5            Q.      Are you aware of any people
 6  associated with Lilly in clinical trials
 7  publishing reports on indicated uses other than
 8  depression?
 9            A.      I'm aware that there are papers
10  published on uses of Fluoxetine in disorders
11  other than depression, I do not know what
12  involvement Lilly has had with those persons.
13            Q.      Are you aware that some of
14  these papers were published prior to Prozac being
15  approved or Fluoxetine being approved for use in
16  depression?
17            A.      I don't know the temporal frame
18  of publications.
19            Q.      Earlier you said that besides
20  Dr. Fawcett there were a number of consultants
21  that Lilly worked with with regards to the issue
22  of depression; correct?
23            A.      Correct.
24            Q.      Can you tell me the names of

                                                 Page 197

 1  some of these other consultants?
 2            A.      One of them was Dr. Rosenbaum,
 3  I believe.
 4            Q.      What's Dr. Rosenbaum's first
 5  name, if you know?
 6            A.      I think it's Jerry, but I'm not
 7  positive.
 8            Q.      Where is he from?
 9            A.      The closest I can get is the
10  east coast.
11            Q.      Anybody else?
12            A.      I believe -- a number of names
13  go through my mind, but I would be guessing.  I
14  do remember Dr. Gary Tollifson as an outside
15  consultant.
16            Q.      He works for Lilly now, doesn't
17  he?
18            A.      He now works for Lilly, yes.
19            Q.      Do you know when he started
20  working for Lilly?
21            A.      I believe it was in 1991.
22            Q.      Do you know if Dr. Tollifson
23  did any work on behalf of Lilly prior to being
24  directly hired by Lilly as an employee?

                                                 Page 198

 1            A.      He served as a consultant to
 2  Lilly prior to joining Lilly.
 3            Q.      Anybody else?
 4            A.      As I say, there are a number of
 5  names that come to mind, although at this point
 6  I'm having a hard time differentiating if I
 7  recall seeing them at Lilly as consultants or I'm
 8  remembering them from the literature so I would
 9  be guessing to give you names at this point, I
10  would prefer not to guess.
11            Q.      How about on the issue of the
12  incidence of suicidal ideation and the use of
13  Fluoxetine, who did you use as consultants on
14  that issue?
15            A.      I thought we were just
16  addressing that issue.
17            Q.      I was under the impression you
18  testified earlier that Dr. Fawcett didn't consult
19  on that issue, that he consulted on the issue of
20  suicidal depression?
21            A.      But I recall saying that I
22  wasn't sure if he had consulted on suicidality
23  and depression.
24            Q.      Okay.  So these other two

                                                 Page 199

 1  people, Dr. Rosenbaum and Gary Tollifson were
 2  consultants on the issue of suicide and suicidal
 3  ideation and the use of Fluoxetine?
 4            A.      If we're comfortable with that
 5  answer, but the other answer, as I said, I feel
 6  like I would be guessing.  So I prefer not to
 7  guess.
 8            MS. ZETTLER:  That's all I have right
 9  now.
10                 * * * * * * * * * *
11                  CROSS EXAMINATION
12 BY MR. SMITH:
13            Q.      Dr. Kotsanos, am I pronouncing
14  that right?
15            A.      That's close enough.
16            Q.      How do you pronounce it?
17            A.      Kotsanos.
18            Q.      Is that Greek?
19            A.      It is.
20            Q.      Have you ever practiced
21  medicine in private practice?
22            A.      I began training in internal
23  medicine, and obviously saw patients during my
24  clinical training, including my preventive

                                                 Page 200

 1  medicine training.  And I see patient, I've begun
 2  seeing patients again at a weekly half-day
 3  medicine clinic.  So the the answer is yes.
 4            Q.      Doctor, my question was --
 5  listen to my questions carefully, I'll try to
 6  talk slow.  That's the only way I can talk
 7  because I only have one speed.  My question was
 8  have you ever practiced medicine in private
 9  practice?
10            A.      The answer is no.
11            Q.      You have seen patients in your
12  experience as a medical physician, though; is
13  that correct?
14            A.      Yes.
15            Q.      And that was in this half-day
16  clinic at Lilly?
17            A.      I've seen patients both in my
18  residency training and I'm now part of a half-day
19  a week medicine clinic that's part of Indiana
20  University.
21            Q.      Do you see patients there?
22            A.      I do.
23            Q.      Do you treat patients there?
24            A.      Yes.

                                                 Page 201

 1            Q.      Prescribe medication?
 2            A.      Yes.
 3            Q.      What type of illnesses do you
 4  treat?
 5            A.      General medicine.
 6            Q.      What would that include?
 7            A.      It's medicine in adults that's
 8  general practice.
 9            Q.      You're Board certified in
10  preventive medicine, aren't you?
11            A.      That's correct.
12            Q.      What are you doing this, is it
13  just some type of pro bono work?
14            A.      It's volunteer work, I do not
15  accept payment, and it's part of a program
16  whereby Lilly encourages its physicians to
17  maintain their hands in clinical practice, a
18  number of physicians do it.
19            Q.      How many hours a week do you
20  spend in that?
21            A.      Well, I just started back doing
22  it, but it's four hours a week approximately.
23            Q.      Four hours a week.  And how
24  long have you been doing that?

                                                 Page 202

 1            A.      Just started again this month.
 2            Q.      How long did you take off from
 3  doing that?
 4            A.      About five or six years.
 5            Q.      Well, you've been with Lilly
 6  since 1988, so it was just this last month, the
 7  only time that you've done that?
 8            MR. MYERS:  That being?
 9            MR. SMITH:  Practice with this clinic
10  in Indiana University.
11            A.      That's the time I just started
12  back to seeing patients in the clinic, yes.
13            Q.      So I want to know, Dr.
14  Kotsanos, how much time you've devoted to patient
15  care where you see patients and render medical
16  advice for patients and prescribe medicine or
17  treatment, how much time have you spent doing
18  that since you graduated as an M.D. in 1984 from
19  Ohio State after you completed your residency and
20  your training?
21            A.      Well, after completing my
22  residency and training, it's been about five or
23  six years to just this month.
24            Q.      So you've not seen any patients

                                                 Page 203

 1  to render medical treatment for those patients on
 2  any basis since you completed your training until
 3  just this last month; is that right?
 4            A.      Not entirely, in that I would
 5  have the opportunity in my position to evaluate
 6  patients, not my patients, but to evaluate
 7  patients in the course of my epidemiology work,
 8  investigating disease outbreaks, for example when
 9  I worked for the Centers for Disease Control, but
10  I did not have a clinic of my own patients where
11  I evaluated them and gave treatment.
12            Q.      If you continue to listen to my
13  question, it would make it easier.  My question
14  was an occasion in which you have been
15  responsible for the care and management of your
16  own patients, and as I understand it that's been
17  limited to just recently within this last month?
18            A.      That's correct.
19            Q.      Have you ever prescribed Prozac
20  for any patients?
21            A.      I have not.
22            Q.      Have you ever seen any patients
23  who were depressed, seen as a medical doctor for
24  these patients?

                                                 Page 204

 1            A.      Certainly during training, I
 2  mean I cannot pinpoint any specific patients now,
 3  but certainly during training I recall seeing
 4  depressed patients.
 5            Q.      I would like -- were you
 6  finished with your answer?
 7            A.      Yes.
 8            Q.      I would like to confine my
 9  questions to those occasions which you rendered
10  medical treatment to patients since your
11  training, all right, can we do that?
12            A.      Yes.
13            Q.      And my question is:  Have you
14  treated any patients for depression?
15            A.      Not since my medical training.
16            Q.      Have you treated any patients
17  who are suicidal, since you completed your
18  training?
19            A.      Again, not since completing
20  medical training.
21            Q.      Let's talk about your medical
22  training since you want to talk about that.  Did
23  you have a psychiatric rotation when you were in
24  training?

                                                 Page 205

 1            A.      Certainly in medical school.
 2            Q.      No.  Did you have a psychiatric
 3  rotation at a hospital when you were in training?
 4            A.      Well, I started training in
 5  general internal medicine, and during that time,
 6  I recall seeing depressed patients.
 7            Q.      No, I'm not asking now whether
 8  you saw depressed patients, I'm asking you
 9  whether or not you had a psychiatric rotation in
10  school?
11            A.      In school or in --
12            Q.      In training.
13            A.      In training.  Training I'm
14  defining as residency training.
15            Q.      Okay.  Let me see if I can make
16  it a little easier for you, Doctor.  If you had
17  training as an internal medicine doctor, I would
18  assume you spent some time in rotation in
19  gastroenterology; correct?
20            A.      Just for your own information,
21  preventive medicine residency requires one year
22  in a clinical field, and I chose internal
23  medicine.  During the internal medicine year,
24  there were no defined rotations in different

                                                 Page 206

 1  particular areas, you treated -- one treated any
 2  internal medicine problem.
 3            Q.      Was psychiatry a part of
 4  internal medicine at that hospital where you
 5  trained?
 6            A.      At the hospital where I
 7  trained, they had a separate psychiatry unit,
 8  although psychiatric patients with medical
 9  problems would come to the medicine ward.
10            Q.      Did you ever treat any
11  psychiatric patients during your training?
12            A.      It's been over five years ago,
13  it's hard for me to remember specific patients or
14  specific treatments, but I'm pretty sure I came
15  across some.
16            Q.      Do you remember rendering any
17  psychiatric advice or treatment for individuals
18  suffering from psychiatric problems?
19            A.      It's been a while, it's hard
20  for me to say yes, I remember specific patients.
21            Q.      Do you in any way, form or
22  fashion consider yourself a psychiatrist, Dr.
23  Kotsanos?
24            A.      No, I do not.

                                                 Page 207

 1            Q.      Do you in any way consider
 2  yourself more knowledgable than the ordinary
 3  medical doctor concerning matters of psychiatry?
 4            MR. MYERS:  Before he answers, let me
 5  object to the form as to what the, quote,
 6  ordinary medical doctor would or would not know,
 7  that would call upon him to speculate as to what
 8  some undefined person or unit would know.
 9            Q.      Do you have any problems with
10  my question, Doctor?
11            A.      I can't answer the question.
12            Q.      Why?
13            A.      I don't know how my knowledge
14  compares with the normal practicing physician.
15            Q.      You don't?  Why, do you not
16  keep up with the normal practicing physician?
17            MR. MYERS:  Same objection as to the
18  form and the undefined normal practicing
19  physician.
20            A.      Despite the limitations of not
21  having had hands-on clinical experience over the
22  past five or six years, I believe my knowledge in
23  different medical and psychiatric areas to be of
24  a level that's comparable to many physicians in

                                                 Page 208

 1  the field due to my attendance at different
 2  conferences, my attendance at grand rounds, my
 3  attendance and discussions with physicians at
 4  Indiana University, teaching epidemiology to them
 5  and engaging in discussions on clinical practice,
 6  to make me feel that my medical knowledge is
 7  comparable to a general practitioner's medical
 8  knowledge.
 9            Q.      You think you know as much
10  concerning psychiatry as the average general
11  practitioner then?
12            MR. MYERS:  Same objection.
13            Q.      And I'm not criticizing that,
14  Doctor.  Obviously there's a lot of general
15  practitioners rendering good medical care.  My
16  question is, I'm trying to define what your
17  experience and what your knowledge is with
18  respect to these matters, and is it accurate when
19  you tell me that you feel your level of expertise
20  concerning these matters is the same as an
21  average general practitioner?
22            A.      I'm guessing, because I don't
23  really know the level of knowledge, like I said,
24  in the beginning.

                                                 Page 209

 1            MR. MYERS:  Don't guess in answer to
 2  any questions.  If you know, tell him, if you
 3  don't, tell him.
 4            A.      I can't answer then.
 5            Q.      Do you not know the general
 6  level of expertise of an ordinary general
 7  practitioner in this state?
 8            A.      The answer is no.
 9            Q.      Do you know the general level
10  of expertise of any particular specialty in
11  medicine other than the epidemiology and
12  preventive medicine?
13            MR. MYERS:  Object as to the form and
14  as to what some undefined physician or group of
15  physicians would know.
16            A.      Could you repeat the question,
17  please?
18            MR. SMITH:  Could you read that back?
19             (THE COURT REPORTER READ BACK THE
20              REQUESTED TESTIMONY.)
21            A.      In order to answer that
22  question, that would require what the general
23  knowledge of physicians in the field is of
24  whatever disease you choose to pick versus my

                                                 Page 210

 1  level of knowledge based on some standard
 2  approach or comparison.  So again, the answer is
 3  I cannot answer that.
 4            Q.      Is it accurate, whatever or
 5  regardless, to state that your level of expertise
 6  with respect to psychiatric matters is not any
 7  greater than that of the ordinary general
 8  practitioner as you understand it?
 9            MR. MYERS:  Same objection.
10            A.      I suppose I have been -- I feel
11  I've been going around in circles on this, but I
12  guess I would give the same answer, and that is I
13  can't answer your question because I don't know.
14            Q.      Is that because you don't know
15  what the ordinary knowledge a general
16  practitioner has concerning the ability to
17  recognize and diagnose psychiatric problems?
18            MR. MYERS:  Same objection.
19            A.      That would be an important
20  starting point to have that type of information.
21            Q.      And you don't have that
22  information?
23            A.      Not information collected
24  systematically on a diverse population of general

                                                 Page 211

 1  practitioners.
 2            Q.      Let me make it a little bit
 3  easier for you.  Do you feel as a medical doctor
 4  competent to diagnose depressive symptoms?
 5            MR. MYERS:  What was the last part,
 6  depressive symptoms?
 7            A.      I believe I could do that.
 8            Q.      Do you feel qualified to make a
 9  diagnosis that an individual is suffering from,
10  quote, clinical depression, end quote?
11            A.      I believe that this would be
12  part of my -- that I could do that.
13            Q.      Do you feel confident as a
14  physician to prescribe anti-depressant
15  medication?
16            MR. MYERS:  Proscribe or prescribe?
17            MR. SMITH:  Right.
18            A.      For some particular medications
19  I would need to refresh my memory on.  Treatment
20  such as tricyclics, however, yes, I feel I could.
21            Q.      You feel competent to prescribe
22  Prozac?
23            A.      Yes, and any other medication.
24            Q.      You wouldn't have any problem

                                                 Page 212

 1  then prescribing anti-depressant medications?
 2            A.      No, I wouldn't have any
 3  problems, to answer the question the way you
 4  asked it.
 5            Q.      And do you think you would have
 6  any problems in selecting a particular
 7  anti-depressant medication?
 8            MR. MYERS:  Under what circumstances?
 9            MR. SMITH:  Under any circumstance.
10            MR. MYERS:  I object to the form, it's
11  over broad.  You earlier asked him could he
12  diagnose depression, and then there was a logical
13  extension, I think, into prescribing.  So
14  prescribe anti-depressants for what?
15            MR. SMITH:  For depression.
16            MR. MYERS:  That's what I asked you.
17            MR. SMITH:  I would assume that would
18  be the only reason you would prescribe an
19  anti-depressant, wouldn't it, would be if an
20  individual was suffering from depression?
21            A.      Could we have your original
22  question restated either by you or --
23            Q.      Do you feel like you're capable
24  of selecting a particular anti-depressant for

                                                 Page 213

 1  treatment of depression?
 2            A.      I believe I could be capable,
 3  but in areas where I would have doubt, I
 4  certainly also know where I would refer or get
 5  help.
 6            Q.      Do you think there might be
 7  some areas in that particular situation where you
 8  would have doubt?
 9            A.      Again, this is all
10  hypothetical.  There could be areas where I would
11  have doubt, I can't think of one, but I'm sure
12  there could be.  And again, it's just a very
13  general hypothetical question, it's hard for me
14  to answer.
15            Q.      Is there some prescribing
16  choice that a physician should make when
17  prescribing a particular anti-depressant for a
18  depressed individual?
19            MR. MYERS:  Let me object to the form
20  and the use of the term some prescribing choice.
21  That is an overly broad term and you haven't
22  given him additional facts in what I think is a
23  hypothetical to form an opinion of what you're
24  asking him.

                                                 Page 214

 1            A.      Could I ask you to repeat your
 2  question, please?
 3            MR. SMITH:  Could you repeat the
 4  question?
 5             (THE COURT REPORTER READ BACK THE
 6              REQUESTED TESTIMONY.)
 7            A.      Again, it's a general question
 8  and without more specifics, I think a general
 9  answer serves, and that is each patient is an
10  individual which requires individual assessment.
11            Q.      If a patient is suicidal, a
12  depressed patient is suicidal, would it be
13  contraindicated to prescribe to that suicidal
14  patient anti-depressant medication?
15            A.      For an actively suicidal
16  patient, clearly my concern would be for the
17  patient and what his actions may be given the
18  treatment regimen that would be decided on for
19  him.  And tricyclic anti-depressants are approved
20  in the use of depression and for depressed
21  patients, so they are approved to use in
22  depressed patients, and suicide is one element of
23  depression.  I don't know how to answer the
24  question better than that.

                                                 Page 215

 1            Q.      I wasn't limiting my question
 2  to tricyclic anti-depressants.  Again, listen to
 3  my question.  My question is:  Would the
 4  prescribing of an anti-depressant be
 5  contraindicated in a patient who is suicidal?
 6            A.      I thought you said tricyclic
 7  anti-depressant.  For a patient with depression,
 8  an anti-depressant would not be contraindicated.
 9  I'm not sure I'm answering your question.
10            Q.      My question is:  Would it be
11  contraindicated to prescribe an anti-depressant
12  to a depressed patient who was suicidal?
13            MR. MYERS:  Do you understand the
14  question?
15            A.      I do now.  Not that I am aware
16  of.
17            Q.      Would it be contraindicated to
18  prescribe psychotherapy to a depressed patient
19  who is suicidal?
20            A.      Again, not that I'm aware of.
21            Q.      Would it be contraindicated to
22  prescribe to a depressed patient who is suicidal
23  a combination of anti-depressant drug therapy as
24  well as psychotherapy?

                                                 Page 216

 1            A.      I'm unaware of any
 2  contraindication.
 3            Q.      Is there any association with
 4  the efficacy of any particular anti-depressant in
 5  combination with psychotherapy?  In other words,
 6  does psychotherapy increase the efficacy of any
 7  particular anti-depressant?
 8            A.      I'm unaware of any data that
 9  supports a difference in efficacy of combining
10  particular anti-depressants with psychotherapy.
11            Q.      Is it your testimony here that
12  there have been no studies that indicate whether
13  or not psychotherapy is beneficial in addition to
14  pharmacological anti-depressant therapy in the
15  treatment of depression?
16            MR. MYERS:  I object to the form, that
17  wasn't your question a minute ago.
18            A.      That wasn't the question.
19            MR. MYERS:  The question was, I think,
20  was there a correlation between the efficacy of
21  the anti-depressants and psychotherapy.  So you
22  have asked two different questions, Paul.
23            MR. SMITH:  What was my last question?
24             (THE COURT REPORTER READ BACK THE

                                                 Page 217

 1              REQUESTED TESTIMONY.)
 2            A.      That is not my testimony here.
 3            Q.      What is your testimony in
 4  connection with respect to whether or not there
 5  have been any studies that indicate that
 6  psychotherapy is of benefit in connection with
 7  pharmacological anti-depressant therapy?
 8            A.      I'm aware that there are
 9  studies that look at psychotherapy alone or
10  anti-depressant therapy alone or combinations of
11  psychotherapy and anti-depressant therapies, all
12  having a degree of efficacy.  But I do not know
13  how those differentiate.
14            Q.      You don't know the results of
15  those studies, is that what you're saying?
16            A.      I don't know them off the top
17  of my head, although I'm sure I could easily find
18  them in the literature.
19            Q.      Is that of any significance to
20  you as an epidemiologist?
21            MR. MYERS:  Close.
22            Q.      In connection with the issue
23  with respect to whether or not Fluoxetine induces
24  suicidal ideation in patients?

                                                 Page 218

 1            A.      Could you repeat the question
 2  again because I just want to make sure it's a
 3  stand alone separate question from the topic we
 4  were just talking about.
 5            Q.      It's a tie-in question.
 6             (THE COURT REPORTER READ BACK THE
 7              REQUESTED TESTIMONY.)
 8            THE WITNESS:  Could you do that again,
 9  please, because I find this question very
10  confusing.
11             (THE COURT REPORTER READ BACK THE
12              REQUESTED TESTIMONY.)
13            A.      Sir, I would like to be able to
14  answer your question, but can you restate it
15  differently, please?
16            Q.      Yes.  I believe you told us
17  earlier that you felt like you were not aware of
18  the efficacy of psychotherapy and pharmacological
19  therapy in treatment of depression; is that
20  right?
21            A.      I believe I said I was aware of
22  such information, but I was unaware of how the
23  efficacy differed between the different
24  therapies.

                                                 Page 219

 1            Q.      So does that make any
 2  difference, that is whether or not they differ or
 3  whether there's any difference in psychotherapy
 4  or pharmacological therapy for treatment of
 5  depression on the issue -- is that important in
 6  examining the issue with respect to whether or
 7  not Fluoxetine induces suicidality in depressed
 8  patients who are not suicidal prior to the
 9  injection of Fluoxetine?
10            A.      I find your question complex,
11  difficult to answer.  I look at them as separate
12  entities, and that is the difference between
13  psychotherapy efficacy versus anti-depressant
14  efficacy.  Knowledge of the differences, if any,
15  in efficacy between those therapies, certainly
16  knowledge of that kind of information influences
17  treatment patterns and also comfort level with
18  treating patients given different therapeutic
19  interventions as psychotherapy and/or
20  chemotherapy.  How that couples with your
21  statement on -- what was it again, Fluoxetine
22  inducing suicidality, something like that.
23            Q.      Uh-huh.  Any relation between
24  the two in your mind?

                                                 Page 220

 1            A.      The way you ask the questions,
 2  I don't see any relation between what you asked
 3  and the first part and second part.
 4            Q.      I guess the reason I'm asking
 5  the question in that manner, and I probably was
 6  being confusing, but I have not seen any reports
 7  concerning any claim at any time that
 8  psychotherapy induced suicidal ideation in an
 9  individual.  Have you ever heard of that
10  occurring?
11            A.      I'm unaware of any reports like
12  that.  Whether or not they exist is another
13  matter, but I'm unaware of any reports like that.
14            Q.      However, you're aware of
15  reports that it was alleged that treatment with
16  anti-depressant Fluoxetine induced suicidal
17  ideation; correct?
18            A.      I'm aware of such a report,
19  reported allegation.
20            Q.      And that was basically the
21  subject of your work at Lilly, is examining that
22  issue, your work at Lilly from 1990 until
23  sometime in 1992; is that right?
24            A.      You mean on Fluoxetine?

                                                 Page 221

 1            Q.      Yes.
 2            A.      About 1990 through 1991, or
 3  '92.
 4            Q.      And that was the issue you were
 5  focused on at Lilly, was that issue concerning
 6  whether or not Fluoxetine induces suicidality in
 7  individuals?
 8            A.      Well, personally I have
 9  detailed my involvement in Fluoxetine safety to
10  Ms. Zettler, and it certainly was a broad
11  approach to many different projects, but I am
12  aware certainly that Lilly has focused a lot of
13  attention at work on that particular question.
14            Q.      Well, you have also, haven't
15  you?
16            A.      I think I mentioned that I was
17  involved in some of the initial designs on the
18  meta-analyses of suicidality that were
19  undertaken.
20            Q.      Well, you were on the advisory
21  committee presentation working group with respect
22  to the FDA investigation on this issue, weren't
23  you?
24            A.      Well, I was involved in a

                                                 Page 222

 1  number of projects and in a number of meetings,
 2  whatever we called the meetings, or however we
 3  categorized people on them, maybe I was, I would
 4  need to see any list that was generated like
 5  that.
 6            Q.      My notes were that you worked
 7  closely in the presentation that Lilly was going
 8  to make to the FDA advisory committee on
 9  suicidality.
10            MR. MYERS:  Are you asking him whether
11  your notes are right or not?
12            Q.      Is that not correct?
13            A.      I think I had mentioned that I
14  was involved in the preparation of a number of
15  backup slides for the FDA advisory committee
16  which took place September of '91.
17            MS. ZETTLER:  Somebody didn't do a real
18  good job of redacting your name off the document.
19            Q.      But you put considerable time
20  towards this issue, haven't you?
21            A.      Yes.
22            Q.      Of whether or not Fluoxetine
23  induced suicidality?
24            A.      I was certainly involved in a

                                                 Page 223

 1  lot of meetings and discussions.
 2            Q.      Talked with the FDA about it?
 3            A.      I was at some of the meetings
 4  with the FDA where discussions took place on it,
 5  yes.
 6            Q.      Have you come to a conclusion
 7  with respect to whether or not Fluoxetine induces
 8  suicidality in individuals who are depressed but
 9  not suicidal prior to ingestion of Fluoxetine?
10            A.      Yes, at this time I believe
11  there's no association in the induction of
12  suicidality by Fluoxetine.
13            Q.      Why do you -- what factors
14  cause you to render that opinion?
15            A.      I think one of the strongest
16  factors is the large meta-analyses undertaken by
17  Lilly of their clinical trial data evaluating
18  this question.
19            Q.      What does meta-analyses mean,
20  M-E-T-A, does that mean big or small?
21            MR. MYERS:  Or something else.
22            A.      You probably would get a better
23  definition from a statistician, although the way
24  I understand it, it is the compilation of a

                                                 Page 224

 1  number of similar studies to increase the size of
 2  the population which is being studied to detect
 3  any differences if in fact they exist.
 4            Q.      So would a meta-analysis be a
 5  broad analysis or a large number of analyses?
 6  I'm just trying to define the term meta, M-E-T-A.
 7            A.      Again, I think you would get a
 8  better definition from a statistician that does a
 9  lot of meta-analyses, however --
10            Q.      Well, I wanted to know what a
11  meta-analysis is.
12            MR. MYERS:  Tell him as best you
13  understand.
14            A.      I would characterize -- again,
15  repeating what I just said, it's a methodology
16  whereby one is looking for -- one is looking to
17  answer a study question and they're pooling a
18  number of different studies so that the size of
19  the sample is increased to increase the
20  probability of detecting any potential
21  differences should they exist.
22            Q.      The theory being the larger the
23  group you study, the better chance you will have
24  in coming to a statistical conclusion or reaching

                                                 Page 225

 1  a particular low-incident group; is that right?
 2            A.      Yes.
 3            MR. MYERS:  I object to the form only
 4  as to the term low-incidence group.
 5            Q.      Less likely to be seen with a
 6  smaller number and more likely to be seen, the
 7  greater number that you examine?
 8            A.      Within the description I gave
 9  you, I believe that's what I'm trying to say,
10  that there's a better likelihood of elucidating a
11  difference should it exist.
12            Q.      And that was significant to you
13  in forming your opinion, was the results or the
14  conclusions reached at the meta-analysis?
15            A.      Well, I think it was an
16  extremely reassuring, the results of the
17  meta-analyses, but also knowledge of the disease
18  entity itself and the fact that suicide is part
19  and parcel of the disease depression making it
20  difficult to sort out that outcome.  Yes, I think
21  there are a number of factors, and that
22  contributes as well.
23            Q.      I'm writing down disease entity
24  itself and I'm putting a question mark by that,

                                                 Page 226

 1  and other factors.  Right now all I want to talk
 2  to you about is the meta-analyses.  Did I hear
 3  you say that you -- that that meta-analysis gave
 4  you greater comfort -- I think I've heard you use
 5  that phrase that I was reassured?
 6            A.      Greater reassurance, sure.
 7            Q.      Reassurance.  That makes me
 8  think that you already had made a decision when
 9  you said the meta-analysis reassured you; is that
10  correct?
11            MR. MYERS:  Is that correct that he
12  said it or is that correct that he made a
13  decision earlier?
14            Q.      That you made a decision
15  earlier.
16            A.      Well, at the time I was working
17  on this, I was more up-to-date on the literature,
18  published studies that looked at issues that were
19  similar.  And as I recall, there were some
20  published studies which tried to address some of
21  these issues.  I'm a little bit foggy on some of
22  them, but for example I seem to recall a Fawcett
23  and Rosenbaum paper on this issue, and having a
24  knowledge of the disease entity -- there are a

                                                 Page 227

 1  number of factors involved in ones understanding
 2  and perception of the disease.
 3            Q.      Let me see if I can put it in
 4  perspective.  In February 1990, Dr. Teicher's
 5  article was published; correct?
 6            A.      If that's the date, yes.
 7            Q.      Does that sound approximate?
 8            A.      Sounds approximately correct.
 9            Q.      And that article theorized that
10  Fluoxetine produced de novo suicidal ideation in
11  depressed patients, did it not?
12            A.      I don't recall if it was de
13  novo suicidal ideation.
14            Q.      New --
15            A.      No, I know what that means, but
16  I don't know, was it new suicidal -- I need to
17  review the paper to refresh my memory.  If it was
18  new or intensification, I don't recall the
19  specifics.
20            Q.      It was your understanding that
21  Dr. Teicher, in that article, was relating the
22  ingestion of Fluoxetine with suicidal ideation,
23  was he not?
24            A.      In general terms.

                                                 Page 228

 1            Q.      And that caused a controversy.
 2            A.      Yes.
 3            Q.      Concerning whether or not that
 4  was accurate; correct?
 5            A.      It certainly raised a question.
 6            Q.      It raised a question in the
 7  scientific community; correct?
 8            A.      He raised the question, Dr.
 9  Teicher raised the question.
10            Q.      And subsequent to that article
11  in February of 1990, lawsuits began to appear
12  where Lilly was named as a defendant?
13            A.      I don't remember when the
14  lawsuits began to appear, but I'm aware of
15  lawsuits appearing after the article.
16            Q.      And those lawsuits claimed that
17  individuals committed suicide or engaged in
18  violent or homicidal acts as a result of the
19  ingestion of Fluoxetine; correct?
20            A.      I'm aware of a number of
21  lawsuits along those lines, correct.
22            Q.      And then there was a scheduled
23  FDA advisory committee to examine this issue?
24            A.      In the next couple of minutes,

                                                 Page 229

 1  if it's convenient, I would like to take a break
 2  so I can call my office before my secretary
 3  leaves at 4:15, but could you repeat that
 4  question, please?
 5            Q.      The FDA, in response to some of
 6  this controversy, called an advisory committee
 7  meeting, did they not?
 8            A.      They called an advisory
 9  committee for anti-depressants in general, and
10  the issue of suicidality.
11            Q.      But Eli Lilly submitted a
12  report on Fluoxetine specifically to the FDA, did
13  they not?
14            A.      Eli Lilly submitted information
15  to the FDA.
16            Q.      And that paper was entitled
17  Emergence of Suicidality During Pharmacologic
18  Treatment of Depression, was it not?
19            MR. MYERS:  If you're reading from
20  something, show it to him, Paul.
21            A.      Which paper, I'm sorry?
22            Q.      I'm talking about the August
23  28th, 1991 submission.  This is what the Lilly
24  lawyers have submitted to us in answers to

                                                 Page 230

 1  interrogatories in a lawsuit down in Texas.  You
 2  know Dr. Talbot, do you not?
 3            A.      Yes, I do.
 4            Q.      And he submitted to Mr.
 5  Burnstein with the FDA this document dated --
 6  well, it was copywrited by Eli Lilly.  Do you all
 7  copywrite most of your stuff that you submit to
 8  the Food and Drug Administration?
 9            A.      I don't know the answer to
10  that.
11            Q.      I'll ask your lawyers sometime.
12  And this is dated August, 1991?
13            A.      That particular page, yes.
14            Q.      Well, the pages are numbered
15  here on the lower right-hand corner.
16            MR. MYERS:  Is the question what the
17  title is?
18            MR. SMITH:  Yes.  You said show it to
19  him, I'm showing it to him.
20            MR. MYERS:  Show him the page you're
21  reading from, Paul.
22            Q.      Page PZ 1548 1973, Emergence of
23  Suicidality During Pharmacologic Treatment of
24  Depression.

                                                 Page 231

 1            A.      Yes, that's correct on this
 2  page, that's what that says.
 3            Q.      And are you familiar with this
 4  submission to the Food and Drug Administration?
 5            A.      May I look through it?
 6            Q.      Certainly.
 7            A.      Because as you're aware, there
 8  were a number of submissions and --
 9            Q.      Do you want to take a break,
10  call your office and glance at that all at one
11  time?
12            A.      That would be good.
13             (A SHORT RECESS WAS TAKEN.)
14            Q.      What participation did you have
15  in that submission to the Food and Drug
16  Administration or did you author parts of it?
17            A.      That's what I was trying to
18  find, if I had authored any parts of it and let
19  me just finish looking through it, please.
20            Q.      We don't want to rush you at
21  all, Doctor.
22            A.      (Witness examines document.)
23  I'm ready.
24            Q.      All right.

                                                 Page 232

 1            A.      What was the last question
 2  again, please?
 3             (THE COURT REPORTER READ BACK THE
 4              REQUESTED TESTIMONY.)
 5            A.      I was involved in the review of
 6  this document, and I was the author, one of the
 7  authors, of appendix H, which is decline in
 8  suicide deaths since Fluoxetine introduction.
 9            Q.      Can I look over your shoulder?
10            A.      Absolutely.  This is the
11  article which ultimately was revised for
12  submission to the American Journal of Public
13  Health.  And I was involved in obtaining drug
14  abuse warning network data, but I don't believe I
15  was the author of this, I believe someone else
16  wrote this.  I can't remember now because I have
17  been involved in preparing some materials on the
18  drug abuse warning network.
19            Q.      This article that you authored
20  is part of the FDA submission that's entitled
21  Decline in Suicide Deaths Since Fluoxetine
22  Introduction, and it's subtitled a manuscript
23  submitted for publication; correct?
24            A.      That's correct, on page one of

                                                 Page 233

 1  appendix H.
 2            Q.      And that's identified as PZ
 3  number 1548, space 2210, and how many pages is
 4  that article?
 5            Q.      It goes through 1548, space
 6  2213; is that right?
 7            A.      Looks like it.
 8            Q.      I mean that is all your
 9  material?
10            A.      I'm one of the authors on it,
11  yes.
12            Q.      Who helped you with that or who
13  was the other author of that?
14            A.      As I mentioned earlier, Dan
15  Masica, Charles Beasley and Dan -- Jan Potvin.
16            Q.      Anything else in that
17  submission that you authored or helped submit?
18            A.      Well, as I just mentioned a
19  couple of minutes ago, I was involved in
20  obtaining some of the data from the drug abuse
21  warning network.
22            Q.      And that's PZ 1548, space 2207;
23  correct?
24            A.      Correct.

                                                 Page 234

 1            Q.      I just got the impression,
 2  Doctor, during your testimony this morning, that
 3  you were called upon by individuals at Lilly to
 4  participate in this submission to the Food and
 5  Drug Administration on the issue concerning
 6  whether or not Fluoxetine induced suicidality in
 7  individuals; is that correct?
 8            A.      Are you specifying that
 9  document or are you specifying that particular
10  study?
11            Q.      Your work load in general
12  consisted primarily of addressing the issue of
13  whether or not Fluoxetine caused suicidality for
14  about a two-year period of time.
15            A.      I was involved in a number of
16  safety projects, and one of them was part
17  involvement in the suicidality question like I
18  stated earlier today.
19            Q.      Can you give me a percentage of
20  your time that was spent on that issue?
21            A.      My time was fairly evenly
22  distributed amongst the different projects I
23  worked on, it's hard to say on what proportion of
24  time I spent on the suicidality, but I think it's

                                                 Page 235

 1  safe to say that of the major projects, it was
 2  probably evenly distributed.
 3            Q.      So what percentage would that
 4  be?
 5            A.      I'll give you a range, maybe
 6  twenty-five to thirty percent.
 7            Q.      Do you know of anybody there at
 8  Lilly that was spending more time on this issue
 9  than you?
10            A.      I don't know what amount of
11  time people spent on each of the projects they
12  worked on.
13            Q.      Do you know if anybody spent
14  any more time on this issue than you did at
15  Lilly?
16            A.      I could only presume and guess.
17            MR. MYERS:  Don't do that.
18            A.      But I won't do that.
19            Q.      Give me your best estimate.  I
20  don't want a guess, but if you can give me an
21  estimate based on some factual basis, I think
22  that would be helpful to us, Doctor.
23            A.      Again, I would be guessing and
24  I would feel uncomfortable guessing.

                                                 Page 236

 1            Q.      Who spent the most time on this
 2  issue, of all the people at Lilly that you dealt
 3  with concerning this issue, who do you feel like
 4  spent the most time facing this issue concerning
 5  whether or not Fluoxetine induced suicidality in
 6  patients?
 7            A.      I have no idea.
 8            Q.      Can you narrow it down to three
 9  or four or five individuals?
10            MR. MYERS:  Paul, he answered the
11  question, he said he had no idea.
12            Q.      Well, do you have anybody that
13  you know of that you feel like was more
14  knowledgable than you concerning this issue?
15            A.      This issue being the one of
16  suicidality?
17            Q.      Yes.
18            A.      Again, I would be guessing by
19  mentioning any names, but I'm sure there are a
20  number of people that put in more time and have
21  more knowledge on the whole area.
22            Q.      Give me their names?
23            A.      As I said, I would be guessing.
24  I think -- I mean, certainly I would not --

                                                 Page 237

 1  certainly I would believe the psychiatrists have
 2  a lot more knowledge and probably put a lot of
 3  time on it, but on a relative basis, I don't know
 4  who's put more time.
 5            Q.      And those psychiatrists in
 6  particular are or were?
 7            A.      The ones we mentioned.
 8            Q.      Those three, Beasley, who else?
 9            A.      Heiligenstein, Wheadon.
10            Q.      What about Leigh Thompson?
11            A.      What's your question about
12  Leigh Thompson.
13            Q.      How much -- did he have more
14  knowledge concerning this issue than you did, as
15  far as you know?
16            A.      I don't know the answer to
17  that.
18            Q.      Tell me about Leigh Thompson,
19  who is -- what was his title when you were
20  working on the Fluoxetine project?
21            A.      I don't remember his official
22  title at that time, but he was overseeing medical
23  research areas.
24            Q.      Any particular aspects of

                                                 Page 238

 1  medical research?
 2            A.      You would -- you're asking me
 3  to reconstruct what the organizational chart
 4  looked like back then, and I can't do that, I
 5  don't remember it.
 6            Q.      I'm just asking you about that
 7  period from 1990 to 1992.
 8            A.      Right, but we've undergone
 9  several different changes, and it's hard for me
10  to remember specifically what it looked like,
11  although I think it's safe to say he was
12  overseeing medical research at that time.
13            Q.      Was he overseeing the medical
14  research in connection with Fluoxetine at that
15  time?
16            A.      Help me understand what's meant
17  by overseeing medical research from the way
18  you're thinking about it.
19            Q.      Well, you were the one that
20  used the term overseeing medical research, so
21  you're going to have to help me.
22            A.      Okay, I'll help you.  I'll
23  state it as saying that those of us in medical
24  research reported to Leigh, reported to Leigh.

                                                 Page 239

 1            Q.      Is it Leigh not Lee?
 2            A.      I think so.
 3            Q.      Like a lei of flowers around
 4  your neck or something; is that right?
 5            A.      Yes.
 6            Q.      Is he also one and the same as
 7  W.L. Thompson?
 8            A.      Yes.
 9            Q.      Did you consider that he, since
10  you were reporting to him, had more knowledge
11  concerning this issue than you did?
12            A.      I can't even guess an answer to
13  that.
14            Q.      Well, since everybody involved
15  in medical research was reporting to him, would
16  you consider that he had more sources of
17  information than you did?
18            A.      I can only assume an answer at
19  this point, and my assumption is yes, he had more
20  sources than I did.
21            Q.      Was there anybody at Lilly at
22  that time, between 1990 and 1992, that you would
23  consider Mr. Prozac or looked to as being the
24  individual most knowledgable concerning Prozac?

                                                 Page 240

 1            MR. MYERS:  I object to the form and
 2  the undefined term Mr. Prozac.
 3            MS. ZETTLER:  That would be you, Larry.
 4            MR. MYERS:  No.
 5            A.      Could you please restate the
 6  question?
 7            Q.      Was there anybody that was
 8  considered by you and your colleagues as being
 9  somebody at Lilly that had a great deal of
10  knowledge concerning Fluoxetine, Prozac, that had
11  been with it, had experience with it for a number
12  of years, had the benefit of a number of reports,
13  number of studies, and was responsible for
14  accumulating a lot of data concerning Fluoxetine?
15            MR. MYERS:  I object to the form only
16  to the extent I think you asked him about three
17  or four questions within that question.
18            MR. SMITH:  I'm just trying to make it
19  easier for him to answer the question.  He said
20  he didn't know what I was talking about first,
21  I'm just trying to help him.
22            A.      I think I understand your
23  question now.  It would be hard for me to
24  pinpoint if there was one particular person who

                                                 Page 241

 1  knew most and more than anyone else about the
 2  drug, there are a lot of knowledgable people
 3  there about the drug.
 4            Q.      Would there be two people?
 5            A.      I would be guessing to give you
 6  a list of names.
 7            Q.      Who would you regularly go to
 8  when you had a question about Prozac?
 9            A.      When I had a question about
10  depression, treatment of depression, Fluoxetine's
11  use in this disease, and the studies ongoing in
12  depression, I would go to one of the three
13  psychiatrists who we've mentioned previously.
14            Q.      Did you ever go to Dr. Zerbe?
15            A.      Maybe, but you've asked me who
16  I would go to, and --
17            Q.      Well, you've already told me
18  about the psychiatrists.
19            A.      Yes.
20            Q.      Dr. Zerbe has been mentioned in
21  answer to interrogatories as being the individual
22  considered by Lilly, as a group, as being most
23  knowledgable concerning Prozac.  Did you ever go
24  to Dr. Zerbe is my question to you?

                                                 Page 242

 1            MR. MYERS:  If the question is did he
 2  go to Zerbe, that's an appropriate question, but
 3  in terms of what was represented or not, I object
 4  to the form because without specifying the
 5  interrogatory, I don't know that what you said is
 6  precise, and I don't think that's the case.
 7            A.      Which is why I answered maybe,
 8  because at one point during that time period, I
 9  reported directly to Zerbe, so I would go to
10  Zerbe for a lot of issues.
11            Q.      What was Zerbe's position at
12  the time you would report to him?
13            A.      I believe he was the executive
14  director of medical, but again, it's been a
15  couple of years and I don't know if that was his
16  exact title.
17            Q.      Did you have any knowledge of
18  anybody at -- of any individual at Lilly who had
19  been involved with Fluoxetine research for the
20  longest period of time?
21            A.      I presume it would be the
22  people who worked on it in the discovery labs and
23  the toxicology labs, people who go way back.
24            Q.      Did you deal with any of those

                                                 Page 243

 1  individuals?
 2            A.      I did not deal with them on a
 3  day-to-day basis.
 4            Q.      Did you deal with them at all?
 5            A.      Never, I never needed to
 6  interact with them.
 7            Q.      How about Ray Fuller?
 8            A.      I remember being present at a
 9  meeting where Ray Fuller was at when we discussed
10  some of these issues, but I never interacted with
11  him.
12            Q.      What age a fellow is Ray
13  Fuller?
14            A.      I have no idea.
15            Q.      You have no idea how old he is?
16            A.      Middle aged.
17            MR. MYERS:  Tell Mr. Smith whether he
18  appears to be older or younger than Mr. Smith, I
19  think that would be some help.
20            Q.      Fifty, sixty?
21            A.      I don't want to appear to be
22  insulting of Dr. Fuller in any way, so let me
23  give you a range, let me give you a range of
24  greater than forty and less than sixty-five.

                                                 Page 244

 1            Q.      How about Dr. Wong?
 2            MR. MYERS:  What about him?
 3            A.      Who?
 4            Q.      Did you deal with Dr. Wong?
 5            A.      I know who Dr. Wong is.  I
 6  again recall being at a meeting or two with Dr.
 7  Wong, but I never had direct interactions with
 8  Dr. Wong.
 9            Q.      What age fellow is Dr. Wong?
10            A.      Same age category as Dr.
11  Fuller.
12            Q.      Was Dr. Fuller and Dr. Wong
13  active in those meetings that you were involved
14  with?
15            A.      There were so few meetings, I
16  mean one or two that I recall being at that they
17  were at, that their activity level was limited
18  from my -- from the work I was doing.
19            Q.      Just to put it in perspective,
20  were you pretty well of the understanding that
21  Dr. Fuller and Dr. Wong were some of the earlier
22  researchers and developers of Fluoxetine
23  hydrochloride?
24            A.      Yes, I was aware of that.

                                                 Page 245

 1            Q.      Did you ever ask either Dr.
 2  Fuller or Dr. Wong if they had any opinion
 3  concerning whether or not Fluoxetine
 4  hydrochloride had any bearing on suicidality for
 5  individuals consuming Fluoxetine hydrochloride?
 6            A.      Personally I don't recall ever
 7  asking them that question.
 8            Q.      Do you know if anybody did?
 9            A.      I do not know.
10            Q.      Did you ever hear them express
11  an opinion concerning this issue one way or the
12  other?
13            A.      I don't recall hearing them
14  express an opinion on it.
15            Q.      Did you ever see them writing
16  something?
17            A.      I don't recall seeing any
18  written opinion by them on it.
19            Q.      How about Dr. Zerbe, do you
20  recall him ever expressing an opinion on this
21  issue?
22            A.      Well, there were a lot of
23  meetings where, you know, Dr. Zerbe was at where
24  the issue was discussed, and I don't recall

                                                 Page 246

 1  specific statements or word that he may have
 2  made, but I believe he was supportive of the
 3  conclusion of the suicide meta-analyses
 4  manuscript.
 5            Q.      Let me back up with you a
 6  little bit.  Did you -- were you asked as part of
 7  your job duties at Lilly to perform any
 8  independent research or make any type of
 9  independent study concerning whether or not
10  Fluoxetine induced suicidality in depressed
11  individuals?
12            MR. MYERS:  I object to the form and
13  the use of the term independent research and
14  independent studies.  What are you talking about?
15            Q.      You, yourself, the witness
16  himself, as an individual or as an employee of
17  Lilly, to do any type of work for Lilly to make
18  the determination concerning whether or not
19  Fluoxetine induced suicidality in any individual?
20            A.      Well, if one defines my efforts
21  that I undertook, for example, in a letter to the
22  editor, resulting in the publication in the
23  American Journal of Public Health, as an
24  independent effort with other Lilly co-authors,

                                                 Page 247

 1  then yes.
 2            Q.      I'm talking about making an
 3  investigation, doing a study, doing research on
 4  this issue.
 5            MR. MYERS:  I think he just answered
 6  that.
 7            A.      Yes, I thought I did.  I think
 8  the answer is yes because that letter to the
 9  editor was an example of a descriptive study.
10  Clearly there were data we collected from the
11  drug abuse -- or DAWN data, D-A-W-N, that looked
12  at descriptive information as well on suicides
13  and overdoses and just general mortality, coupled
14  with prescription use data.  Sure, we've done, to
15  use your words, independent research.
16            Q.      And that's involved looking at
17  data; is that correct?
18            A.      Exactly.
19            Q.      Looking at data collected by
20  Lilly?
21            A.      Actually the original raw data
22  were collected by the federal government and
23  other sources, and it was compiled in these data.
24            Q.      Well, the raw data that's

                                                 Page 248

 1  collected by the federal government is what?
 2            A.      Well, for example, suicide
 3  mortality data collected and provided by the
 4  federal government, prescription-use data
 5  collected by a, I believe it's a private company,
 6  although I'm not sure, that surveys, you know,
 7  prescription use of multiple different drugs, for
 8  that particular paper as an example.
 9            Q.      What's the private company?
10            A.      It's IMS.
11            Q.      IMS?
12            A.      Yes.
13            Q.      What's that stand for?
14            A.      I don't remember, although we
15  referenced it in our letter to the editor, which
16  you can find there.  I think it's National
17  Prescription Audit, but I don't remember what IMS
18  stands for.
19            Q.      Where is that company from?
20            A.      I don't know their main
21  location.
22            Q.      And they're --
23            A.      Well, at one time I knew it
24  because I obviously contacted them, but I don't

                                                 Page 249

 1  recall it right now.
 2            Q.      Are they a company that just
 3  has a function of collecting data on the number
 4  of prescriptions written for particular drugs?
 5            A.      I do not know, I cannot answer
 6  that.
 7            Q.      What is your understanding of
 8  what they do?
 9            A.      At the time, I had a very good
10  understanding, but I've forgotten the details of
11  how the company works and how they collected the
12  data.  But if I needed to know, I could go back
13  and reconstruct it by calling them.
14            Q.      So you got that data -- the
15  data you got from them was number of
16  prescriptions written for Fluoxetine; is that
17  right?
18            A.      That's one component of the
19  data, sure.
20            Q.      What else did you get from
21  them?
22            A.      That's all we got from that one
23  company.  We obviously also collected mortality
24  data from federal government sources.

                                                 Page 250

 1            Q.      What sources at the federal
 2  government?
 3            A.      Publications of mortality data.
 4  Again, all referenced in the letter to the editor
 5  we wrote.
 6            Q.      What other data did you get?
 7            A.      I think I mentioned the DAWN
 8  data.
 9            Q.      That's Drug Abuse Warning
10  Network?
11            A.      Something like that.
12            Q.      Is that -- who publishes that
13  now?
14            A.      I think it's the national
15  institutes for drug abuse, but I'm not exactly
16  positive.  We could simply look at their
17  publication and clarify that.
18            Q.      What else?
19            A.      Well, obviously the clinical
20  trial data or data that are generated by Lilly.
21            Q.      What else?
22            A.      I should back up because as I
23  recall, your initial question is was what I was
24  involved in generating.  I was not involved in

                                                 Page 251

 1  generating the clinical trial data.  I'm still
 2  thinking about --
 3            Q.      But you reviewed that data --
 4            A.      No.
 5            Q.      -- in coming to a conclusion
 6  and making an investigation concerning this
 7  issue; is that correct?
 8            A.      Yes.  Published studies as
 9  well.
10            Q.      Published studies?
11            A.      Uh-huh, yes.
12            Q.      That would be studies published
13  on what?
14            A.      On the disease depression and
15  its natural history and its course in both
16  treated and untreated patients.
17            Q.      Do you believe it's the natural
18  course of untreated depression that an individual
19  commits suicide?
20            A.      Absolutely.  I believe that
21  suicide is an integral part of the disease
22  depression.
23            Q.      My question is:  Do you believe
24  it's the natural course of untreated depression

                                                 Page 252

 1  that an individual will commit suicide?
 2            A.      Not necessarily in all
 3  individuals.
 4            Q.      In a percentage of individuals?
 5            A.      I cannot recall figures that
 6  are published.
 7            Q.      Do you think that's a high
 8  percentage?
 9            A.      I believe it's a relatively
10  high percentage.
11            Q.      So I can understand this, is it
12  your belief and opinion that a high percentage of
13  individuals who are not treated for depression
14  will end up committing suicide?
15            MR. MYERS:  I object to the form only
16  to the extent that high has not been defined by
17  anybody.
18            MR. SMITH:  It was his term.
19            MR. MYERS:  No, you used the term.
20            A.      Again, it's all subjective
21  based on what one would define as high.
22            Q.      Was there subjective input into
23  this analysis, into this investigation that you
24  made?

                                                 Page 253

 1            A.      I don't understand what you
 2  mean by subjective input.
 3            Q.      You say it's all subjective
 4  with respect to what you mean by high.  Did you
 5  use any subjective analysis in making this
 6  investigation concerning whether or not
 7  Fluoxetine induced suicidality?
 8            MR. MYERS:  I object to the form.
 9  Again, I don't know that subjective analysis is
10  defined.
11            A.      I don't understand the
12  question.  If you can repeat it, please, maybe a
13  little differently.
14            Q.      Well, you were of the opinion
15  that a percentage of individuals who are
16  depressed who are not treated for that depression
17  will end up committing suicide; is that right?
18            A.      Well, that's a subjective
19  opinion, but, yes.
20            Q.      Any other subjective opinions
21  that you fit into this analysis that you made
22  concerning whether or not suicidality can be
23  induced by ingestion of Fluoxetine?
24            A.      I do not recall if there are

                                                 Page 254

 1  any subjective opinions put in -- written
 2  anywhere, or whatever.
 3            Q.      You mentioned the clinical
 4  trial data that you reviewed, you mentioned the
 5  published data, and I assume that's data
 6  published in scientific articles?
 7            A.      Scientific peer review
 8  journals, yes.
 9            Q.      What other data did you use?
10            MR. MYERS:  Are you having a recap or
11  other than what he's told you?
12            Q.      Other than what you've told me.
13            A.      At this time, I cannot recall
14  anything else other than what we've discussed.
15            Q.      That clinical trial data that
16  you used was the U.S. clinical trial data, wasn't
17  it?
18            A.      The meta-analyses that were
19  published in the British Medical Journal were
20  U.S. clinical trial data.
21            Q.      Did you ever consult the
22  clinical trial data in actual studies at any time
23  concerning this issue?
24            A.      Personally, I did not, but I

                                                 Page 255

 1  was not involved in that component of the
 2  project.
 3            Q.      Don't you agree that if you
 4  consulted the international data that you would
 5  have more data upon which to review, upon which
 6  to formulate an opinion on this issue?
 7            A.      That seems like a hypothetical
 8  question, but hypothetically yes, there would be
 9  more data available.
10            Q.      Lilly expended a great amount
11  of time, money and effort to conduct
12  international clinical trials outside the United
13  States, didn't they?
14            A.      I'm aware that Lilly conducted
15  clinical trials outside of the United States.
16            Q.      And you don't have any reason
17  to doubt the accuracy or the authority or the
18  authenticity of those trials done outside the
19  United States at Lilly's direction and bequest,
20  behest, do you?
21            A.      Since I was not involved in the
22  review of those data, I can't really comment on
23  it.
24            Q.      Why didn't you review those

                                                 Page 256

 1  data, I guess is the point?
 2            A.      I just wasn't involved in that
 3  component of the project, I was involved in a
 4  number of things.  And again, there's only so
 5  much an individual can do.
 6            Q.      Do you know of anybody at Lilly
 7  that did review the international clinical trial
 8  data in connection with this issue on whether or
 9  not Fluoxetine causes suicidality?
10            A.      I do not know who I could point
11  you to at Lilly about that issue.
12            Q.      Who would you ask if you went
13  to the office tomorrow and wanted to know whether
14  or not anybody reviewed the international
15  clinical trials concerning this issue and who did
16  it?
17            A.      I might start with, again, the
18  psychiatrists.
19            Q.      Do you know if any of those
20  psychiatrists did any review of the international
21  clinical data to make any formulation of an
22  opinion concerning this issue?
23            A.      I do not know, but you're
24  asking me who would I ask, and that's where I

                                                 Page 257

 1  would start.
 2            Q.      The meta-analysis that you base
 3  your data on and your opinion on, didn't include
 4  all the clinical U.S. trials that Lilly did, did
 5  it?
 6            A.      Could you repeat that, please?
 7            Q.      The meta-analysis of which you
 8  speak didn't include all the clinical trials done
 9  in the United States, did it?
10            A.      I believe that's correct.
11            Q.      Do you know why all of the
12  clinical trials were not included?
13            A.      I believe one of the key
14  reasons was based on the methodology used in
15  meta-analyses, and that is to identify protocols
16  that are similar in nature.  And not all the
17  clinical trials were similarly designed which
18  would allow more correct combination of these
19  clinical trials.
20            Q.      Don't you --
21            A.      For example, there may have
22  been pharmacokinetic clinical trials, which are
23  studying blood levels, and it's not studying
24  necessarily the safety and efficacy as another

                                                 Page 258

 1  clinical trial would studied.  So it's a method
 2  that employs a combination of studies that are
 3  similar in nature in terms of their design and
 4  outcome.
 5            Q.      Did the meta-analysis review
 6  all the data concerning individuals who had
 7  ingested Fluoxetine and had been observed after
 8  that ingestion of Fluoxetine in the clinical
 9  trials?
10            MR. MYERS:  In which clinical trials,
11  Paul?
12            MR. SMITH:  In the meta-analysis.
13            A.      I was going to ask the same
14  question.  Could you restate it now, I'm sorry?
15            Q.      Maybe I'm confused on what the
16  meta-analysis reviewed.  I would think that the
17  meta-analysis would review all informative data
18  concerning whether or not Fluoxetine caused
19  suicidality.  Are you convinced that it did?
20            A.      I'm convinced that the methods
21  undertaken were very appropriate in terms of the
22  meta-analyses to study the question.  So, yes, I
23  believe that the methods undertaken are
24  scientifically sound.

                                                 Page 259

 1            Q.      Well, were they all inclusive
 2  with respect to the individuals in the clinical
 3  trials that experienced suicidal ideation?
 4            MR. MYERS:  I object to the form.
 5            Q.      Or did they leave out some of
 6  those?
 7            MR. MYERS:  I object to the form
 8  because are we talking about the trials that were
 9  included in the analysis or are you talking about
10  trials that were not included in the analysis?
11            MR. SMITH:  All the trials.
12            A.      Again, I believe that the
13  methods employed were scientifically sound
14  methods to identify the studies that were
15  included in this meta-analysis, to follow a
16  systematic approach of identifying similar
17  protocols, which to combine, there were some
18  trials that were not included, studies that may
19  have still been ongoing which wouldn't be
20  appropriate to include them, studies that, like I
21  mentioned, may be measured and had the outcome of
22  just looking at blood levels.  And again, it's
23  not looking at safety and efficacy, so --
24            Q.      Why would an ongoing study not

                                                 Page 260

 1  be included?
 2            A.      An ongoing study may not have
 3  the outcomes identified that one is looking for
 4  in terms of safety, efficacy.
 5            Q.      The ongoing study had a report
 6  of suicidal ideation.  Wouldn't that be of
 7  significance in the issue?
 8            A.      Let me go back.  I mentioned
 9  that as an example, that is ongoing studies.  But
10  I would need to review the meta-analyses
11  manuscript to clarify if those ongoing studies
12  were included or not to see if the methods were
13  that way.
14            Q.      Do you follow where I'm going
15  with it?  In my questioning you concerning the
16  meta-analyses, my concern is that the
17  meta-analysis might not have included some of the
18  clinical trials that had information that would
19  be informative with respect to whether or not
20  Fluoxetine induces suicidality.  Do you know of
21  any such study that was done and omitted from the
22  meta-analysis that would have information that
23  would be informative on the issue with respect to
24  whether or not Fluoxetine induces suicidality?

                                                 Page 261

 1            MR. MYERS:  I object to the form and
 2  the term informative as being undefined, and I
 3  also object to the form in that he's testified a
 4  couple of times as to what trials the
 5  meta-analysis included and why they included
 6  those trials.  So the others have been excluded
 7  by definition, I think.
 8            A.      I don't know how to answer your
 9  question any better except to say I'm of the
10  opinion that the methods undertaken were
11  scientifically sound with the trials that were
12  included to address the question.
13            Q.      I'm talking about do you have
14  any concern whether or not there were some
15  clinical trials that weren't evaluated in that
16  meta-analysis that might have been informative
17  concerning the issue of whether or not
18  suicidality and Fluoxetine have a causal
19  connection?
20            A.      Well, in the meta-analyses, the
21  methods were very appropriate that were
22  undertaken.  For the trials that may not have
23  been included in the meta-analyses, they were all
24  analyzed, as I seem to recall, and summarized for

                                                 Page 262

 1  the FDA.
 2            Q.      And some were eliminated?
 3            MR. MYERS:  I object to the form,
 4  that's not what he said.
 5            Q.      I thought you said some were
 6  excluded, and that was --
 7            THE WITNESS:  Could you please repeat
 8  what I said because now I don't remember what I
 9  said.
10             (THE COURT REPORTER READ BACK THE
11              REQUESTED TESTIMONY.)
12            Q.      So you're saying there were
13  trials in the meta-analysis that were not
14  included, but they were summarized?
15            MR. MYERS:  I object to the form,
16  that's not what he said.
17            A.      That's not what I said.
18            Q.      We may be on a completely
19  different wave length, I suspect we are.  Clarify
20  for me.
21            A.      I said that of the population,
22  the world of clinical trials, for the methods of
23  meta-analyses, the trials were identified that
24  had similar methods, and used in the

                                                 Page 263

 1  meta-analyses to address the question.  For any
 2  other trials that weren't part of the
 3  meta-analyses, due to not fitting that
 4  appropriate methodology, they certainly were
 5  summarized for the FDA.
 6            Q.      Can we leave it that there were
 7  some U.S. clinical trials that were not discussed
 8  in the meta-analyses?
 9            A.      I would have to review the
10  meta-analyses to see exactly what was said about
11  the trials that were included and those not
12  included before I can leave it that way.
13            Q.      So there are some trials that
14  were included and some trials that were not
15  included?
16            A.      And I believe --
17            Q.      Is that correct?
18            A.      That's correct.
19            Q.      All right.  That's it on that.
20  Are there any clinical studies being done by
21  Lilly or at Lilly's direction at this time that
22  you're aware of that are perspectively analyzing
23  or studying whether or not Fluoxetine induces
24  suicidal ideation or suicide attempts?

                                                 Page 264

 1            A.      I'm unaware of any as I'm not
 2  working in that area.
 3            Q.      Who would be the individual
 4  most knowledgable at Lilly concerning whether or
 5  not there are any perspective studies currently
 6  under way on this issue?
 7            A.      Presumably the executive
 8  director of the division.
 9            Q.      And who is that?
10            A.      Dr. Gary Tollefson.
11            Q.      Are you not doing anything in
12  connection with Prozac at this time?
13            A.      Well, as I stated earlier, my
14  involvement has been from the health economics
15  research division perspective in terms of
16  participating in cost effectiveness, decision
17  analysis models.
18            Q.      Let me ask you about that.
19  When you're talking about cost, there's some cost
20  effectiveness decision and analysis model
21  currently ongoing in connection with Prozac?
22            A.      There's the pursuit of doing a
23  cost effectiveness decision analysis project with
24  an outside consultant, but I don't believe a

                                                 Page 265

 1  contract has been signed yet.
 2            Q.      Who is that outside consultant?
 3            A.      Well, we've been in discussion
 4  with one outside consultant, but there's been no
 5  contract signed yet to the best of my knowledge.
 6            Q.      Who is that outside consultant?
 7            A.      I think they're Health
 8  Technology Associates.
 9            Q.      And what specifically are they
10  going to do?
11            A.      They're going to frame an issue
12  of the appropriateness and cost effectiveness
13  treatments of depression, and they are going to --
14  again, they will have rights on designing
15  whatever outcomes they want, but presumably it
16  will look at the total health care picture of
17  depression, the treatment patterns and the
18  outcomes, and assign probabilities of these
19  different treatment patterns and outcomes, and
20  use it to calculate a number of outcome
21  parameters, primarily cost effectiveness.
22            Q.      You're going to have to convert
23  that to me.
24            A.      I know, it probably didn't make

                                                 Page 266

 1  any sense.
 2            Q.      Talk to me like I was a high
 3  school senior interested in studying health and
 4  depression, and now tell me what you just told
 5  me.
 6            MR. MYERS:  You know, Paul, before he
 7  answers, he went over this at length before the
 8  lunch break.
 9            MR. SMITH:  And I didn't understand it
10  then either.
11            MR. MYERS:  See if you can simplify it
12  for Mr. Smith.
13            A.      Let me take a different example
14  altogether.  Let's say you wanted to know the
15  population of people in the United States that
16  had condition X.  And there are a number of
17  factors that influence condition X, for example --
18  this is clearly out of the sky, but let's say
19  they need to be smokers to have condition X or
20  they need to be on contaminant medications to
21  have condition X.  Well, all of a sudden you've
22  identified your problem, and that is you want to
23  know how many people in the population have
24  condition X, for whatever reason, whether it's

                                                 Page 267

 1  for figuring out what kind of person power you
 2  need to intervene in condition X.  You need to
 3  know the size of condition X in order to estimate
 4  what kind of influence you can have on condition
 5  X, but you need to start way back at the
 6  beginning and say what's the size of the
 7  population.  Well, the census figures tell me
 8  there are two hundred and fifty million people in
 9  the United States, plus or minus some range of
10  error.  Then you next need to know of the people
11  in the United States how many of them are
12  smokers.
13                    Well, you have that percentage,
14  plus or minus some type of range of error.  Then
15  you need to know of the people who smoke, how
16  many have condition X, and you have that number
17  with some range of error.  And each time you
18  start generally and move your way forward to the
19  outcome of interest, you have a number with this
20  range of uncertainty coupled with the next number
21  with its range of uncertainty, and you start
22  integrating all these numbers, multiplying them
23  or adding them, whatever is necessary, computer
24  program will do it for you, and you integrate

                                                 Page 268

 1  this uncertainty forward, where you ultimately
 2  get your number of interest with its associated
 3  uncertainty.
 4                    So at the end, you may say gee,
 5  there are a hundred thousand people in the United
 6  States that have condition X, plus or minus
 7  whatever range of error.  More likely what you'll
 8  say is, there's a fifty percent chance that there
 9  are at least a hundred thousand people in the
10  United States with condition X, and you may say
11  that we don't have the budget to intervene in
12  condition X if it's greater than a certain
13  amount.
14                    Now the data that you look for
15  are the population cencus data, the number of
16  smokers, are data that come from the literature.
17  If you don't have those data in the literature, a
18  lot of times the numbers don't exist in the
19  literature, you convene expert panels to get
20  their best guess or you conduct surveys to get
21  people's estimate on what those numbers are or
22  the way treatment is administered.  And you
23  factor all these numbers and their uncertainties
24  and you get your outcome of interest.  Does that

                                                 Page 269

 1  help you?
 2            Q.      It makes it a little clearer to
 3  me.  Now convert that to depression and Prozac
 4  and what this group is doing for you or has
 5  proposed doing for you?
 6            A.      Well, we've actually initiated
 7  looking at this.  And what they would presumably
 8  do is look at the cost effectiveness of treatment
 9  of depression by different categories of
10  treatments, whether it be tricyclic
11  anti-depressants, seritonin uptake inhibitors,
12  and/or even untreated patients.  You have three
13  arms for which you have to feed the model with
14  data from the literature, and those data would be
15  everything from what are the medical care
16  resources that the average patient has and what
17  are the outcomes that the average patient has.
18            Q.      So you're looking at how many
19  depressed individuals there's going to be in the
20  future?
21            A.      No.
22            Q.      Okay.
23            A.      It's usually categorized as a
24  retrospective study because they gather data

                                                 Page 270

 1  that's already existing in the literature.
 2  However, those data will change because medical
 3  care is always an evolving science and -- it's
 4  not really a future projection of number of
 5  depressed patients.
 6            Q.      How does the cost effectiveness
 7  come into this?
 8            A.      It looks at the -- looks at the
 9  total medical care of a depressed patient, and it
10  looks at the medical care resources consumed in
11  the treatment of a depressed patient.  Whether or
12  not the medical care resources are associated
13  with depression, and there may be differences
14  based on treatment groups, and that's the premise
15  of the model.
16            Q.      How does that impact Lilly and
17  Prozac?
18            A.      Oh, you need to understand that
19  the traditional approach of studying drugs, that
20  is looking at safety and efficacy, is needed for
21  regulatory agencies, and also physicians.  But
22  emerging customers, large HMO's, foreign
23  governments, are requiring cost effectiveness
24  data.  So those types of data are needed for all

                                                 Page 271

 1  of our products, not just Prozac, in order to
 2  meet the customers' needs.
 3            Q.      Okay.  So you say there may be
 4  an HMO in the future that you are going to need
 5  to submit data to concerning the number of
 6  depressed individuals that they might have and
 7  what the most cost effective means of treating
 8  those individuals is or will be?
 9            A.      That could be one approach,
10  sure.
11            Q.      Is it accurate, is it accurate?
12            MR. MYERS:  Is what accurate, the
13  statement or --
14            MR. SMITH:  He said that could be one
15  approach, I just want to make sure it's an
16  accurate approach or is it too simplistic?
17            A.      Let's go back to your question
18  before, is it accurate, and maybe I can rephrase
19  my answer differently.
20            Q.      Is it accurate?
21            A.      Before your question is it
22  accurate.
23            MR. MYERS:  Do you want the original
24  question?

                                                 Page 272

 1            A.      Well, I guess the statement you
 2  made, is it accurate, you said something to the
 3  effect that HMO's need to know the number of
 4  depressed people and something else --
 5            Q.      The most cost effective method
 6  to treat those individuals.
 7            A.      HMO's are clearly -- HMO's,
 8  plus foreign governments, are clearly very
 9  interested in the cost effectiveness of the
10  medical therapies, and in some cases require
11  getting that type of information when it comes to
12  deciding whether or not to put a product on their
13  formulary.  Does that help you?
14            Q.      What is putting a product on a
15  formulary mean?
16            A.      It typically means that the
17  product will be reimbursed or it's available for
18  prescription or use.
19            Q.      All right.  So you're wanting
20  to ensure that these HMO's will approve Prozac as
21  a recommended treatment or as a permissible
22  treatment for depression?
23            MR. MYERS:  I object to the form, that
24  mischaracterizes what his testimony was and his

                                                 Page 273

 1  answer to the last two questions.
 2            Q.      Maybe it is a
 3  mischaracterization, I'm just trying to
 4  understand what your testimony is, I'm not
 5  seriously intending to mischaracterize.
 6            MR. MYERS:  Subject to my objection, if
 7  you can answer the question as put to you, go
 8  ahead and do that.
 9            A.      Essentially what we're doing is
10  generating additional outcome data, outcome data
11  beyond safety and efficacy, which tends to be
12  these cost effectiveness outcomes, and/or quality
13  of life outcomes, that governments, manager care
14  groups, other groups, are expecting to see with
15  medical care treatments which are proposed and
16  ultimately, hopefully, with this additional data
17  it will continue to provide health care
18  practitioners with additional data so they can
19  make the most appropriate patient care decision
20  they can.  And at the same time, obviously, these
21  data will be used in discussions with customers
22  who ultimately buy or have influence on the
23  products used.  It serves a couple of purposes.
24            Q.      Do any of those studies or does

                                                 Page 274

 1  any of that analysis analyze the issue or data
 2  concerning whether or not Fluoxetine induces
 3  suicidality?
 4            A.      I do not believe any of those
 5  studies look at the issue of Fluoxetine induction
 6  of suicidality, no.
 7            MS. ZETTLER:  How about as estimated?
 8            MR. MYERS:  Of?
 9            MS. ZETTLER:  Suicidality.
10            THE WITNESS:  I do not believe any of
11  those studies look at the exascerbation of
12  suicidality of Fluoxetine.
13             (A SHORT RECESS WAS TAKEN.)
14            Q.      Doctor, the concept of
15  rechallenge is a valid concept in doing research
16  with respect to whether or not there's cause and
17  effect in connection with a particular drug or a
18  particular disease, is it not?
19            A.      In general, when one looks at
20  causality, there are a host of factors involved
21  with thinking about causality,
22  challenge-rechallenge, being one factor of many.
23            Q.      It's of scientific importance,
24  is it not, that concept of challenge-rechallenge?

                                                 Page 275

 1            MR. MYERS:  I object to the form, what
 2  do you mean by scientific importance?
 3            Q.      Well, it can form the basis of
 4  a scientific decision, can it not?
 5            A.      I believe that
 6  challenge-rechallenge is a additional collection
 7  of data which can contribute to a whole picture
 8  of thinking about challenge-rechallenge.  But in
 9  addition, a biological plausability and a whole
10  host of other factors.
11            Q.      When you go to an allergist and
12  that allergist scratches your back with several
13  different types of substances to determine what
14  you're allergic to, that's sort of a
15  challenge-rechallenge type of investigation by
16  the allergist, is it not?
17            A.      That seems a little different
18  to me as an example.
19            Q.      If you go to a cardiologist and
20  the cardiologist does a stress test on an
21  individual, that's sort of a
22  challenge-rechallenge type of analysis, is it
23  not?
24            A.      If the cardiologist is using

                                                 Page 276

 1  exercises as the stressor to induce anginal chest
 2  pains and EKG changes, and notices them and then
 3  redoes it, and reduplicates that, I presume
 4  that's a challenge-rechallenge type of anomaly.
 5            Q.      And that's a indicator of the
 6  presence of heart disease?
 7            A.      It could be.
 8            Q.      It's certainly valid for a
 9  cardiologist to perform a stress test on an
10  individual suspected of having heart disease, is
11  it not?
12            A.      A stress test can be one
13  component of an evaluation of heart disease.
14            Q.      It's certainly a reasonable
15  component of that evaluation, isn't it?
16            A.      It can be one reasonable
17  component of an evaluation depending on the
18  presentation of the patient.
19            Q.      Certainly, but stress tests are
20  used all the time, aren't they, Doctor, by
21  cardiologists to make some type of a diagnostic
22  impression concerning whether or not an
23  individual is suffering from heart disease, are
24  they not?

                                                 Page 277

 1            A.      I do not know if they're used
 2  all the time, although I know they are used in
 3  the assessment of a patient with heart disease on
 4  occasion.
 5            Q.      It's medically acceptable to do
 6  that in the right medical circumstances, isn't
 7  it?
 8            A.      I agree with that.
 9            Q.      And it's also medically
10  acceptable for the allergist to subject an
11  individual to various, what is it, contaminants,
12  or -- what would be the word where -- do you know
13  what I'm talking about, are we on the same wave
14  length?
15            A.      We are.
16            Q.      What is that?
17            A.      Antigens or allergens, skin
18  test is what you're referring to.
19            Q.      That's a reasonable way to
20  determine whether or not an individual happens to
21  be allergic to a particular allergen, isn't it?
22            A.      Well, I don't think that's
23  entirely correct for the allergic example,
24  because I think a skin test may indicate that

                                                 Page 278

 1  someone's been exposed to a particular allergen,
 2  but whether or not it's clearly a true allergen
 3  which elicits allergic symptoms in a patient is
 4  another story.
 5            Q.      But it is certainly useful in
 6  making some determination on the issue, isn't it?
 7            A.      Can be helpful at times.
 8            Q.      And so can a rechallenge under
 9  the circumstances that was being discussed by the
10  Food and Drug Administration with respect to the
11  issue, with respect to whether or not Fluoxetine
12  causes suicidality, that was a reasonable
13  suggestion on their part, was it not?
14            MR. MYERS:  Before he answers, let me
15  object to the form to the extent that you're
16  trying to equate his testimony on an allergen
17  skin test with what was or wasn't proposed by the
18  FDA.  That would be a mischaracterization of his
19  testimony.
20            A.      Clearly, many different studies
21  can be proposed, but evaluation and assessment of
22  different study approaches needs to be
23  undertaken.
24            Q.      And this was an evaluation of a

                                                 Page 279

 1  rechallenge study, wasn't it, that was being
 2  discussed in May of 1991?
 3            A.      This what, please?
 4            MR. MYERS:  Are you referring to
 5  Exhibit 1?
 6            MR. SMITH:  Yes, the subject of this
 7  memo.
 8            A.      I must admit in point one,
 9  entitled Proceed With The Rechallenge Study, the
10  details indicated in the bullet point are not
11  very clear to elucidate the thought process that
12  took place, and it may or may not be complete
13  with enough information to make judgments on the
14  whole tenor of the discussion.  It was an attempt
15  of mine to try to capture what I thought I heard
16  at the meeting, although it may not be as
17  detailed as it certainly seems to need to be at
18  this point.
19            Q.      At the time, didn't you feel
20  like you were making a reasonable attempt to
21  capture the essence of the meeting in your memo
22  of May 15th, the subject of Plaintiff's Exhibit
23  1, Kotsanos Exhibit 1?
24            A.      I believe I made a reasonable

                                                 Page 280

 1  attempt, although as we went over earlier, for
 2  example the first bullet point under point one, I
 3  mean I'm the worst critic of my work, it's not
 4  clear to me what's being said there, so there's
 5  potential problems with the wording.
 6            Q.      Well, are you saying that this
 7  is an inaccurate or incomplete or shoddy piece of
 8  work on your part, Doctor?
 9            MR. MYERS:  I object to the form,
10  that's not what he's saying, not what he has
11  said.
12            MR. SMITH:  Then he can answer it by
13  saying no, that's not what he's saying.
14            A.      It's not a shoddy piece of
15  work, it certainly could be incomplete to the
16  point where more descriptive details would be
17  helpful at this point to answer the types of
18  questions that you're asking.
19            Q.      Do you think that you wrote any
20  other memos concerning the proposed rechallenge?
21            A.      You know, I don't recall if I
22  did, and if I did, you certainly should have them
23  somewhere.
24            Q.      This is the only one we found.

                                                 Page 281

 1            A.      Then this is apparently the
 2  only one I've written.
 3            Q.      So we've got to work with what
 4  we've got, don't we, Doctor?
 5            A.      And I'm trying.
 6            MR. MYERS:  What's the question?
 7            Q.      The meetings that were held
 8  with the FDA occurred on May 13th, 1991; is that
 9  right?
10            A.      According to this memo, that's
11  correct.
12            Q.      Does that comport with your
13  recollection?
14            A.      I recall going to the FDA, but
15  I don't recall the date.
16            Q.      Do you have any reason to
17  believe, Doctor, that May 13th, 1991 is
18  inaccurate with respect to when this meeting
19  occurred?
20            A.      I have no reason to believe
21  that it's inaccurate.
22            Q.      Where did the meeting occur?
23            A.      I believe that it was at the
24  FDA headquarters.

                                                 Page 282

 1            Q.      Where?
 2            A.      Rockville, Maryland.
 3            Q.      You were present at that
 4  meeting?
 5            A.      Yes.
 6            Q.      Who else was there from Lilly?
 7            A.      Well, as I believe, I may have
 8  attended two meetings at the FDA.  It's hard for
 9  me to recall which particular people were at
10  which meetings, although I can recall some faces
11  and names.  The question is, is it this meeting
12  or another meeting, I don't know.
13            Q.      Were there two meetings where
14  the subject of rechallenge came up?
15            A.      Not that I recall.
16            Q.      Was there more than one meeting
17  where the subject of Fluoxetine and suicidality
18  came up?
19            MR. MYERS:  That he attended?
20            MR. SMITH:  Yes.
21            A.      As I said, I'm pretty sure that
22  was the purpose of both meetings.
23            Q.      And in one meeting, the meeting
24  in May, obviously the issue of rechallenge came

                                                 Page 283

 1  up; is that a reasonable reading of your memo?
 2            A.      Yes.
 3            Q.      My question to you is:  Who
 4  with Lilly was at that May meeting?
 5            A.      I would be guessing, we would
 6  need to get a formal -- a copy of formal minutes
 7  that detail attendees and agenda objectives.
 8            Q.      Where would those formal
 9  minutes be?
10            A.      I would assume they would exist
11  in our regulatory documents as either a note to
12  file or copies of letters and correspondence.
13            Q.      Who would have been the one
14  that would have been keeping these formal meeting
15  minutes?
16            A.      Well, that would be our
17  regulatory group.
18            Q.      Then was somebody there from
19  your regulatory group?
20            A.      Probably, yes, but which
21  individual it was, I don't know, I would be
22  guessing.
23            Q.      How many times while you were
24  working on this issue did you go to Rockville,

                                                 Page 284

 1  Maryland to discuss this issue with the Food and
 2  Drug Administration?
 3            MR. MYERS:  Which issue, rechallenge?
 4            MR. SMITH:  Yes.
 5            A.      Or suicidality?
 6            Q.      Rechallenge.
 7            A.      Well, obviously this is one
 8  meeting that is documented.
 9            Q.      Right.  Can you picture in your
10  mind's eye being in there, being at this meeting
11  at the FDA speaking of rechallenge in Rockville,
12  Maryland in the Washington, D.C. area at the Food
13  and Drug Administration?
14            A.      Well, obviously discussion took
15  place at the meeting as per the meeting minutes.
16            Q.      My question is:  Can you
17  picture being there discussing?
18            A.      I can picture being at a
19  meeting in the FDA.
20            Q.      In the Spring of 1991?
21            A.      As I said, I have been there
22  before, but -- so, I can remember being there,
23  that's for sure.
24            Q.      What size room were you in?

                                                 Page 285

 1            A.      Probably a room a little bit
 2  smaller than this room.
 3            Q.      How did you get there?
 4            A.      Took a plane.
 5            Q.      Did anybody fly on the plane
 6  with you from Lilly?
 7            A.      I suspect so, sure.
 8            Q.      Who?
 9            A.      You have to understand, I have
10  made more than one trip, and it's --
11            Q.      You told me about two.
12            A.      Well, I also attended the FDA
13  advisory committee meeting.
14            Q.      Well, that was in September of
15  1991, wasn't it?
16            A.      Sure.
17            Q.      We're talking about in the
18  Spring of 1991, before the advisory committee
19  meeting.
20            A.      And I would like to tell you
21  who I think was at this meeting.  Although I can
22  picture names and people, but whether or not each
23  of the names I would tell you about were at this
24  particular meeting, I couldn't really say.

                                                 Page 286

 1            Q.      Tell me who you think was at
 2  that meeting in May, 1991, at the FDA, where
 3  rechallenge was discussed.
 4            MR. MYERS:  If you can do so without
 5  guessing, tell him.  If you don't know, tell him
 6  that.
 7            A.      I can't do so without guessing
 8  or presuming.
 9            Q.      Are you telling me that you
10  can't give me anything better than a guess with
11  respect to who was at -- let me finish my
12  question.  With respect to who was at the May
13  15th, 1991 meeting?
14            A.      No.
15            Q.      All right.  Then if your answer
16  is no, that means you can tell me who was with
17  you based on a reasonable estimate.
18            A.      I said no, I couldn't give you
19  better than a guess.
20            Q.      So yes, it would only be a
21  guess?
22            A.      That's right.
23            Q.      Look at the names of those
24  individuals there, and we're going to do

                                                 Page 287

 1  everything in our power to help you with this,
 2  that are listed on the memo.  Do you have any
 3  recollection of any of those gentlemen being
 4  there with you at the meeting?
 5            A.      Anything I say would be a pure
 6  guess.  I mean there are some people on this list
 7  that I wouldn't see why they would have been
 8  there, so --
 9            Q.      Well, can you picture in your
10  eye getting on the plane here in Indianapolis and
11  going to Washington for this meeting?
12            A.      I have been to Washington, D.C.
13  so many times since I've worked here for many
14  different occasions, and big groups on many
15  occasions, that you're asking me to reconstruct
16  something that's hard for me to do, I've told you
17  that numerous times.
18            Q.      Well, nobody promised you this
19  would be easy.  My question to you is:  How many
20  times then have you been to Washington, D.C.
21  since you've been employed by Eli Lilly, and met
22  with representatives of the Food and Drug
23  Administration?
24            A.      Over a half dozen times.

                                                 Page 288

 1            Q.      Over six?
 2            A.      Yes.
 3            Q.      More than ten?
 4            A.      Probably not.
 5            Q.      How many times have you been to
 6  the Food and Drug Administration in Washington,
 7  D.C. this year, 1993?
 8            A.      No times.
 9            Q.      How many times did you go last
10  year, 1992?
11            A.      I do not believe I was there in
12  1992.
13            Q.      How many times in 1991 did you
14  go?
15            A.      I suppose of the six to ten
16  times I have been to the FDA, I believe they
17  occurred over a three-year period of 1989, 1990,
18  1991, although that's pushing my memory and there
19  may be one or two of those times in early '88,
20  but I don't recall.
21            Q.      Maybe three times a year in
22  1991, 1990 and 1989?
23            A.      Maybe.
24            Q.      How many times did you go to

                                                 Page 289

 1  the Food and Drug Administration in Washington,
 2  D.C. in the Spring with the cherry blossoms?
 3            MR. MYERS:  Of what year?
 4            Q.      1991, 1990, or 1989.
 5            A.      I can't recall specifically,
 6  you have to be aware that I have been to
 7  Washington, D.C. on occasion of seven times a
 8  year unrelated to the FDA.  So it's hard for me
 9  to always keep straight why I have been to
10  Washington.  If you really want accurate
11  information, I need to reconstruct my trips
12  through billing data or whatever.
13            Q.      Do you keep any kind of daily
14  log with respect to your activities in your
15  employment at Eli Lilly?
16            A.      I do not keep a daily log in my
17  employment with Eli Lilly and Company.
18            Q.      Do you keep an appointment
19  calendar?
20            A.      None that I keep permanently,
21  just use it on a daily basis.
22            Q.      Is that written or is that
23  computerized?
24            A.      The daily log, you mean, it's a

                                                 Page 290

 1  computerized calendar.
 2            Q.      Do you purge it at the end of
 3  the year?
 4            A.      I don't know how it works, you
 5  know, how long data are kept in it.
 6            Q.      Do you remember doing any work
 7  in preparation for the May 13, 1991 meeting?
 8            A.      The one thing I remember is
 9  working with Charles Beasley on reviewing the
10  MSSIR scale and having discussions with the
11  consultant from Brown University, and even having
12  this consultant into Lilly regarding the temporal
13  frame of when I talked to Dr. Ivan and -- Dr.
14  Ivan Miller.  And this meeting, I cannot
15  reconstruct that here from memory.
16            Q.      All right.  So you don't have
17  any idea who from Lilly was with you at this May
18  13, 1991 meeting?
19            MR. MYERS:  Paul, he said two or three
20  times he doesn't recall.  Now move on to
21  something else.  One more time, answer it one
22  more time and that's it.
23            A.      Short of guessing, I cannot
24  recall.

                                                 Page 291

 1            Q.      Do you remember who from the
 2  Food and Drug Administration was present at this
 3  meeting?
 4            A.      Well, in my trip report -- or,
 5  I'm sorry, in this meeting summary, Dr. Leber and
 6  Dr. Stadel were mentioned, and those are two or
 7  at least were two FDA employees at the time.
 8            Q.      Do you remember any other Food
 9  and Drug Administration employees there?
10            A.      There were always more than
11  just two FDA employees present at the meetings,
12  but I don't recall specifically who that may have
13  been.
14            Q.      Can you recall generally who it
15  might have been?
16            A.      I would presume it would be the
17  people that are the psychiatrists that worked
18  with Dr. Leber.
19            Q.      I know you can't remember
20  names, but do you remember whether or not you had
21  a Lilly psychiatrist with you there at that
22  meeting?
23            A.      I would presume at least one of
24  them was present at that meeting.

                                                 Page 292

 1            Q.      You listed Dr. Beasley.  That's
 2  the only psychiatrist I see listed on this list.
 3            A.      Dr. Wheadon is listed as well
 4  on this address list.
 5            Q.      Okay.  Oh, W-H-E-A-D-O-N?
 6            A.      Yes.
 7            Q.      Any other psychiatrists on that
 8  list?
 9            A.      There are no other
10  psychiatrists listed on this address list.
11            Q.      Incidently, there are numbers
12  by each one of these individual's names?
13            A.      Yes.
14            Q.      Like twenty-one twenty-eight by
15  Dr. Beasley's name?
16            A.      Yes.
17            Q.      What does that number denote?
18            A.      It's a mail drop code.
19            Q.      For the E-Mail?
20            A.      No, mailbox.
21            Q.      The title of the -- well, let
22  me go back now with you.  We know who Dr. Beasley
23  is, who is Dr. Enas, E-N-A-S?
24            A.      Dr. Enas is a statistician at

                                                 Page 293

 1  Lilly.
 2            Q.      Do you have any recollection of
 3  him being at that meeting?
 4            A.      I do not know if he was at that
 5  particular meeting or not.
 6            Q.      Mr. S.M. Harrill,
 7  H-A-R-R-I-L-L, who is that?
 8            A.      Mike Harrill is a manager of
 9  clinical research administrators.
10            Q.      Do you have any recollection of
11  him being at the May 13th meeting?
12            A.      I do not recall if Mike Harrill
13  was at that meeting.
14            Q.      Dr. C.V. Sampson.
15            A.      Dr. Charlie Sampson is a
16  statistician.  At the time he was director of the
17  statisticians, and whether or not he was
18  specifically at this meeting, I would only be
19  guessing.
20            Q.      Dr. Max Talbot?
21            A.      Director of regulatory affairs.
22            Q.      Do you have any recollection
23  with respect to whether or not Dr. Talbot was
24  with you?

                                                 Page 294

 1            A.      As I mentioned earlier, I would
 2  presume one of the regulatory representives would
 3  have been there, whether it was Max Talbot or Al
 4  Weber, I do not recall.
 5            Q.      Dr. Archie Thompson?
 6            A.      Dr. Bob Thompson is a clinical
 7  research physician at Lilly.
 8            Q.      Do you have any opinion with
 9  respect to whether or not he would have been at
10  the meeting?
11            A.      I do not recall if he was
12  working on Fluoxetine at the time I was working
13  on it.
14            Q.      Why would he have been listed?
15            A.      It's a good question, I do not
16  recall.
17            Q.      Dr. W.L. Thompson, that's Dr.
18  Leigh Thompson?
19            A.      Dr. Leigh Thompson.
20            Q.      Do you have any recollection
21  with respect to whether or not he was at that
22  meeting on May 13, 1991?
23            A.      Certainly it would come down to
24  either Leigh or Bob Zerbe being present at the

                                                 Page 295

 1  meeting, but which of them or both of them were
 2  present at that particular meeting, I do not know
 3  or recall.
 4            Q.      Dr. J.A. Weber?
 5            A.      I mentioned him earlier, he's
 6  one of the regulatory scientists.
 7            Q.      Dr. A.J. Weinstein?
 8            A.      Dr. Weinstein at the time was a
 9  vice-president in the medical area.  I do not
10  recall him being at this meeting.
11            Q.      Dr. D.E. Wheadon,
12  W-H-E-A-D-O-N?
13            A.      Dr. Wheadon was one of the
14  clinical research physicians and a psychiatrist.
15            Q.      Do you have any recollection
16  with respect to whether or not -- you said he was
17  a --
18            A.      As I said, certainly one of the
19  psychiatrists was present.
20            Q.      Either Beasley or Wheadon would
21  have been there?
22            A.      Or even Heiligenstein, but I
23  don't remember.
24            Q.      Well, he's not listed.

                                                 Page 296

 1            A.      I noticed that, I don't know
 2  why.
 3            Q.      Ms. C.  Zapapas?
 4            A.      Carol Zapapas, department head
 5  of the clinical research administrators in that
 6  area.
 7            Q.      Do you have any recollection of
 8  her being there?
 9            A.      No.
10            Q.      And Dr. Zerbe?  You think
11  either he or Leigh Thompson would have been at
12  the meeting?
13            A.      It would have been one of them.
14            Q.      Did you object to doing a
15  rechallenge study with respect to Fluoxetine and
16  suicidality?
17            A.      I don't recall if I objected or
18  concurred at that time with doing a study like
19  that.
20            Q.      Did you ever object or concur
21  in the necessity of doing that type of study?
22            MR. MYERS:  Anytime?
23            MR. SMITH:  Yes.
24            A.      I suppose the answer is it's

                                                 Page 297

 1  possible, but I don't recall.
 2            Q.      Okay.  And what would have been
 3  your decision, would you have either been for
 4  that or been against a study of that nature?
 5            A.      I don't know, it seems like a
 6  hypothetical question at this point in trying to
 7  reconstruct what my thought process was back
 8  then.
 9            Q.      What's your thought process
10  now?
11            A.      I haven't given a lot of
12  thought to the study design, I would want to give
13  it a lot of thought to give any type of answer to
14  it.  I think there would be a lot of issues to
15  consider, I would want to talk to a lot of people
16  about it.  So I guess at this point, I don't have
17  an opinion on it.
18            Q.      Did you have an opinion then?
19            A.      It wasn't a project I was
20  working on directly, so I don't know if I had an
21  opinion then.
22            Q.      Help me understand why you were
23  the one that was writing all this down and the
24  author of the memo if you weren't intimately

                                                 Page 298

 1  involved in this?
 2            MR. MYERS:  I'm going to object, he
 3  answered that this morning as to why he wrote the
 4  memo at least twice.
 5            MR. SMITH:  I don't remember what it
 6  was, if he did, I didn't understand it at the
 7  time.
 8            A.      I summarized the meeting to the
 9  best of my ability and distributed it.
10  Typically, meeting minutes are summarized after
11  such visits and I had -- I must have had some
12  time to do it and did it, and it certainly served
13  to provide others my perception of the meeting
14  outcome.
15            Q.      Was this something that was
16  assigned that you do?
17            MR. MYERS:  He's answered that as well.
18  Go ahead and answer it again.
19            A.      I think my -- what I said
20  earlier, my recollection was I don't know if
21  anyone particularly assigned me to do this.
22            Q.      Do you recall if anybody from
23  the Food and Drug Administration there was
24  keeping notes?

                                                 Page 299

 1            A.      They may have been, I don't
 2  recall.  They typically summarize their own
 3  session.
 4            Q.      Would you have handwritten
 5  notes that you made there at that meeting?
 6            A.      I do not recall if I
 7  specifically had handwritten notes from this
 8  meeting, I wrote the summary fairly quickly after
 9  the meeting which seems to me maybe I didn't.
10            Q.      It's dated May 15th.
11            A.      Right, two days after the
12  meeting.
13            Q.      So you just don't know whether
14  you had handwritten notes or not?
15            A.      If I did and it were part of
16  the file, I would suspect that they would be in
17  existence.
18            Q.      Did you ordinarily keep your
19  handwritten notes after you dictated a memo of
20  this nature?
21            A.      I do take notes at some
22  meetings, but not all meetings.  I tend to
23  dictate a lot or type, you know, type my
24  summaries on computer, so it depends.

                                                 Page 300

 1            Q.      The first sentence says:  At
 2  the FDA meeting literally need to do the
 3  following projects.  One, proceed with the
 4  rechallenge study.  That sounds to me like Lilly
 5  is agreeing with the request made by the Food and
 6  Drug Administration that they engage in a
 7  rechallenge study.
 8            A.      That's the way the wording
 9  seems to indicate.
10            Q.      Is that your recollection of
11  what occurred?
12            A.      I would have to defer to the
13  memo as opposed to my recollection from two years
14  ago.
15            Q.      This memo?
16            A.      Yes.
17            Q.      This memo would be your best
18  recollection?
19            A.      It was my interpretation of
20  what I thought I heard.
21            Q.      And as I understand it, you
22  have a recollection of being in a conference room
23  at Rockville, Maryland when this was discussed?
24            A.      Yes.

                                                 Page 301

 1            Q.      The first sentence after the
 2  bullet one says:  We need to collect data to
 3  characterize the patients who are both enrolled
 4  and not enrolled in this study to determine if
 5  there are differences between those patient
 6  groups.  Had there been a study begun on May 13,
 7  1991?
 8            A.      None that I'm aware of -- I'm
 9  sorry, you mean a rechallenge study?
10            Q.      Yes.
11            A.      None that I'm aware of.
12            Q.      Why then did you use this
13  wording we need to collect data to characterize
14  the patients who are, quote, both enrolled and
15  not enrolled in the study, end quote, to
16  determine if there are differences between these
17  patients, patient groups?
18            A.      As I mentioned earlier, on
19  retrospect, in reading this bullet point, it's
20  not very clear, it's hard for me to reconstruct
21  what the thought process was.
22            Q.      But your best recollection is
23  there wasn't some organization to the extent that
24  you would actually enroll some patients?

                                                 Page 302

 1            A.      That's right, there was no
 2  study that I was aware of.
 3            Q.      You say we've agreed to have
 4  the rechallenge protocol ready to go by September
 5  1st, 1991; correct?
 6            A.      The third bullet point under
 7  point number one does say we agree to have the
 8  rechallenge protocol ready to go by September 1,
 9  1991.
10            Q.      Did you do any work on a
11  rechallenge protocol?
12            A.      I did not do any work on a
13  rechallenge protocol.
14            Q.      Do you know if anybody at Lilly
15  did any work on a rechallenge protocol?
16            A.      I think I mentioned earlier
17  that I was aware of a preliminary or initial
18  draft of such a protocol.
19            Q.      Who did that initial draft?
20            A.      My guess would be one of the
21  psychiatrists.
22            Q.      Now, was the modified scale for
23  suicidal ideation going to be used in the
24  rechallenge study?

                                                 Page 303

 1            A.      I do not recall specific
 2  discussion about that, it may have been and it
 3  may not have been.
 4            Q.      Do you know if the modified
 5  scale for suicidal ideation was used in any
 6  studies done by Lilly for any purposes in
 7  connection with Fluoxetine research?
 8            A.      I do not know if the modified
 9  scale for suicidal ideation or the modified scale
10  for suicidal ideation revised was used or is
11  being used in any Lilly studies.
12            Q.      Who would know that?
13            A.      Again, I would defer to one of
14  the psychiatrists at Lilly.
15            Q.      It says here or you say here,
16  the FDA was interested in including the MSSIR in
17  clinical trials in the UK to understand if this
18  issue is uniquely American or broader in scope.
19  Do you recall using that language?
20            A.      You read it verbatim from the
21  paper.
22            Q.      When you are talking about this
23  issue, you're talking about the suicidality issue
24  in connection with Fluoxetine, aren't you?

                                                 Page 304

 1            A.      That seems to be the context in
 2  which this is written, although it's -- again,
 3  it's too bad it wasn't two years ago when we were
 4  having this discussion.
 5            Q.      Who raised the idea that this
 6  suicidal ideation might be something that was,
 7  quote, uniquely American, end quote?
 8            A.      I do not recall who raised the
 9  issue.
10            Q.      You do recall it being raised,
11  though, that this suicidality might be something
12  that's distinctly only to Americans?
13            A.      I don't even recall that
14  discussion, but certainly it's captured in these
15  minutes so there was obviously some discussion on
16  that.
17            Q.      Under point three on page two,
18  there's a mention of Dr. Teicher and Dr. Cole;
19  correct?
20            A.      Their names are mentioned, yes.
21            Q.      Were either of these gentlemen
22  at the meeting?
23            A.      I don't think so.  I don't
24  recall, but I don't think so.

                                                 Page 305

 1            Q.      Have you ever talked with Dr.
 2  Teicher or Dr. Cole?
 3            A.      I have personally never talked
 4  to Dr. Teicher.  I do not recall if I ever
 5  personally spoke with Dr. Cole.
 6            Q.      Do you think you might have?
 7            A.      Again, it gets back to the
 8  discussion we had earlier where I mentioned that
 9  there were several psychiatrists at different
10  times that were consulted on different issues,
11  and it's possible Dr. Cole was at one of these
12  sessions, and if he was, there was a possibility
13  I may have spoke with him, but I don't have any
14  specific recollection of having any conversations
15  with him.
16            Q.      Have you ever sought to make an
17  appointment with Dr. Teicher concerning his
18  observations?
19            A.      I personally never did.
20            Q.      Did you ask somebody to do
21  that?
22            A.      I never asked anybody to do
23  that.
24            Q.      Did you ever talk to anybody at

                                                 Page 306

 1  any time while employed with Eli Lilly and
 2  Company who had experienced suicidal ideation
 3  following ingestion of Prozac?
 4            A.      I do not recall if I spoke with
 5  anyone, any patient specifically who had had
 6  suicidal ideation following ingestion of Prozac.
 7  It's possible, given that on occasion we would
 8  receive phone calls from people with adverse
 9  event records.  Typically patients that were
10  reporting adverse event reports would call into
11  the drug epidemiology unit.  On rare occasion, we
12  would get phone calls from patients.  On a more
13  common occasion, the research physicians would
14  get calls from the physicians of the patients.
15  So it's possible, but I don't recall any specific
16  discussions I had with patients about suicidal
17  ideation.
18            Q.      Do you ever recall
19  investigating with any particular patient who had
20  experienced suicidal ideation, the issue of
21  whether or not that suicidal ideation was caused
22  by ingestion of Fluoxetine?
23            MR. MYERS:  What do you mean by
24  investigating?

                                                 Page 307

 1            MR. SMITH:  Questioning that patient.
 2            A.      I don't recall ever personally
 3  questioning any patients.
 4            Q.      Did you ever talk with any
 5  physician who had had a patient who had committed
 6  suicide while on Fluoxetine treatment?
 7            A.      I was involved in the
 8  evaluation of numerous adverse event reports,
 9  some of them where I did talk with physicians.
10  But I cannot recall specifically if any of them
11  were about suicidal ideation or committing
12  suicide by the patient with the physician.
13            Q.      I'm talking about a worst case
14  scenario, Doctor.
15            A.      Sure.
16            Q.      Where a doctor, a physician,
17  had reported to you that a patient of his had
18  committed suicide, died, while on Fluoxetine
19  treatment?
20            A.      It's possible, but I don't
21  recall any specific instance.
22            Q.      What's your best judgment --
23  anything is possible.  Do you have any specific
24  recollection of talking with any doctor whose

                                                 Page 308

 1  patient had died while being treated with
 2  Fluoxetine?
 3            MR. MYERS:  He's answered that twice.
 4            MR. SMITH:  No, he's not answered it
 5  yet.
 6            MR. MYERS:  Yes, he has.
 7            A.      No, I don't have any specific
 8  recollection.
 9            Q.      Did you make any investigation,
10  did you go talk with any doctors, to determine
11  any details concerning any patient who had
12  committed suicide while being treated with
13  Fluoxetine?
14            A.      It's very possible I may have
15  had discussions like that, but I recall having a
16  lot of discussions with physicians reporting
17  adverse events, and I don't recall specifically.
18            Q.      I'm not talking a lot of
19  discussions with a lot of physicians regarding a
20  lot of adverse events, I'm talking about suicide --
21  suicidal ideation or suicide attempts while a
22  patient was on Fluoxetine therapy, Doctor?
23            A.      I don't recall specifically if
24  I had such conversations.

                                                 Page 309

 1            Q.      Did you go to any hospital at
 2  any time to investigate a report of an individual
 3  overdosing on any type of drug while on
 4  Fluoxetine therapy?
 5            A.      I did not go to any hospital to
 6  evaluate what you described.
 7            Q.      Did you ever leave the city of
 8  Indianapolis, Indiana to make any determination
 9  at all with respect to whether or not any
10  particular patient was experiencing suicide,
11  suicidal ideation or attempted suicide while on
12  Fluoxetine treatment?
13            A.      Can you clarify your question,
14  please?  When you say to make any attempt, do you
15  mean by visiting physicians or patients or
16  hospitals or do you mean an attempt to understand
17  the disease depression and the investigation of
18  it?
19            Q.      I'm talking about attempted
20  suicide or suicidal ideation.
21            A.      You mean visiting either
22  physicians or patients?
23            Q.      Yes.  Did you ever go outside
24  Indianapolis, Indiana to talk to physicians,

                                                 Page 310

 1  patients or hospitals?
 2            A.      Not to evaluate that specific
 3  issue.
 4            Q.      Who at Lilly was charged with
 5  investigating whether or not a particular
 6  attempted suicide, suicide or suicidal ideation
 7  was causally related to Fluoxetine?
 8            A.      There was usually a team
 9  approach whereby persons in the drug epidemiology
10  unit, that is the CRA's, clinical research
11  administrators, in the drug epidemiology unit
12  would take adverse event reports and/or the
13  clinical research physicians would take adverse
14  event reports, and the clinical research
15  physicians would evaluate all of the adverse
16  event reports and make assessments about the
17  reports, regarding need for additional
18  information and medical judgments in that regard.
19            Q.      Did you as a clinical research
20  physician ever -- or assistant clinical research
21  physician, ever request additional information
22  concerning any particular report of suicide,
23  suicide attempt, or suicidal ideation by an
24  individual being treated with Fluoxetine therapy?

                                                 Page 311

 1            A.      I recall requesting additional
 2  information on many such reports.
 3            Q.      All right.  In connection with
 4  suicide and Fluoxetine?
 5            MR. MYERS:  You're now talking about --
 6  you said suicide, suicide attempt, suicidal
 7  ideation a minute ago.
 8            MR. SMITH:  I guess I should have added
 9  all three of them to the last question.
10            A.      For any adverse event report
11  which included -- which includes suicide,
12  suicidal ideation --
13            Q.      But I'm not wanting to include
14  it, I'm wanting to limit it to those kinds of
15  reports.
16            A.      I recall, in general,
17  requesting additional information on some of the
18  reports of suicidality of patients on Fluoxetine.
19            Q.      What in general do you recall
20  about that additional information you were
21  requesting?
22            A.      I recall requesting as much
23  clinical information as is possibly obtainable
24  from the person who reported the adverse event.

                                                 Page 312

 1            Q.      Okay.  If that was a doctor, it
 2  would be the medical records?
 3            A.      Or simply a discussion with the
 4  physician or a request in writing for the
 5  information, a number of different approaches.
 6            Q.      Who usually got that
 7  information for you?
 8            A.      Again, it would depend on the
 9  adverse event.  But one approach was to have the
10  clinical research administrators in the DEU
11  telephone or write to the physicians for that
12  additional information.  Additionally, on
13  occasion, I would make phone calls for
14  information by contacting the physician, the
15  reporting physician.
16            Q.      Did you ever leave that up to
17  the drug detail people?
18            A.      What do you mean, I'm sorry?
19            Q.      Getting that information.  Did
20  you ever leave that to the detail people?
21            A.      I never recall asking them to
22  find that type of information for us.
23            (DISCUSSION OFF THE RECORD.)
24            MR. MYERS:  I have conferred with the

                                                 Page 313

 1  witness and with Ms. Huff, and based on the
 2  discussion that we had off the record among
 3  counsel and some general representations as to
 4  how long the deposition might or might not
 5  continue, we're going to adjourn the deposition.
 6  We will endeavor to work with you all to arrive
 7  at some agreement as to the recommencement of the
 8  deposition at a date after the transcript is
 9  received, subject, hopefully, to some agreement
10  as to the scope and duration of any continued
11  deposition, and if we can't agree, then one or
12  other of us would simply have to apply to one of
13  several courts for some ground rules on that.  I
14  really don't know what else to do because I just
15  think having commenced at or about 9:00 o'clock
16  and it now being 6:45 p.m., I just think it would
17  be most appropriate to try to -- well, to
18  adjourn, and to either make an accommodation or
19  to simply seek some relief on the subject.
20            MR. SMITH:  We agree that it has been a
21  long day and it would probably be most
22  expeditious to look at the transcript.  We know
23  we have more lines of questioning, but hopefully
24  once we get the transcript we'll be able to look

                                                 Page 314

 1  at that more closely and give you some idea of
 2  what we'll need and how long we'll need, and
 3  maybe we can have an agreement.  If not, we all
 4  have relief with various courts.
 5            MR. MYERS:  That's right, I think
 6  that's the best solution to the problem.
 7            MS. ZETTLER:  No further questions.
 8            MR. RUIZ:  No questions.
 9            MS. LAWS:  No questions.
10            MR. CLEMENTI:  No questions.
11            MR. BALLENTINE:  No questions.
12            MR. KRAUS:  No questions.
13             (THE WITNESS WAS EXCUSED.)

                                                 Page 315

 1 
   COMMONWEALTH OF KENTUCKY        )
 2                                 :  ss
   COUNTY OF JEFFERSON             )
 3 
 4       I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN
 5  AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY
 6  CERTIFY THAT THE FOREGOING TESTIMONY OF
 7                  JAMES KOTSANOS, M.D.
 8  WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS
 9  STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST
10  DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH,
11  AND NOTHING BUT THE TRUTH; THAT THE SAID
12  PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC
13  NOTES AND AFTERWARDS TRANSCRIBED UNDER MY
14  DIRECTION; THAT IT IS A TRUE, COMPLETE AND
15  CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO
16  HAD; THAT THE APPEARANCES WERE AS STATED IN THE
17  CAPTION.
18       WITNESS MY SIGNATURE THIS THE 5TH DAY OF
19  SEPTEMBER, 1993.
20       MY COMMISSION EXPIRES MARCH 10, 1994.
21 
   
22 
   
23                _________________________
                  MARY KATHLEEN NOLD
24                COURT REPORTER AND NOTARY PUBLIC
                  STATE OF KENTUCKY AT LARGE

                                                 Page 316

 1 
 2 
 3               E R R A T A   S H E E T
 4 
   
 5 STATE OF INDIANA              )
                                 : SS
 6 COUNTY OF                     )
   
 7 
 8            I, JAMES G.  KOTSANOS, THE UNDERSIGNED
 9  DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES
10  OF MY DEPOSITION AND WITH THE CHANGES NOTED
11  BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND
12  ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON
13  THE AUGUST 16, 1993 AT THE TIME AND PLACE STATED
14  THEREIN.
15 PAGE NO.     LINE NO.     CHANGE          REASON

                                                 Page 317

 1 
 2 PAGE NO.     LINE NO.     CHANGE          REASON
   
 3 
   
 4 
   
 5 
   
 6 
   
 7 
   
 8 
   
 9 
                    _____________________________
10                  JAMES G. KOTSANOS
   
11            SWORN TO AND SUBSCRIBED BEFORE ME THIS
12  _____ DAY OF __________, 1993.
13            _____________________________
              NOTARY PUBLIC, STATE OF
14            INDIANA AT LARGE

                                                 Page 318

 1 
 2 
 3 
 4 
 5 
 6 
 7 
 8 
 9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 

                                                 Page 319

 1 
 2 
 3 
 4 
 5 
 6 
 7 
 8 
 9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 

                                                 Page 320

 1 
 2 
 3 
 4 
 5 
 6 
 7 
 8 
 9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 

                                                 Page 321

 1 
 2 
 3 
 4 
 5 
 6 
 7 
 8 
 9 
10 
11 
12 
13 
14 

                                                 Page 322