Food and Drug Administration
Center for Drug Evaluation and Research
Summary Minutes of the
Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee
of the Advisory Committee for Pharmaceutical Science
8120 Wisconsin Ave., Bethesda, MD.
April 23, 2002
M. Michael Wolfe, M.D., Chair Joel Richter, M.D.
David Colin Metz, M.D. Byron Cryer, M.D.
Robert Alan Levine, M.D. John Thomas LaMont, M.D.
Jurgen Venitz, M.D. Gloria Anderson, Ph.D., Consumer Rep.
Peter Gross, M.D. Brian Leslie Strom, M.D., M.P.H.
Ruth S. Day, Ph.D. Jacqueline Gardner, Ph.D., M.P.H.
Eric S. Holmboe, M.D. William H. Campbell, Ph.D.
Stephanie Y. Crawford, Ph.D. Michael R. Cohen, R.Ph., M.S., D.Sc.
Thomas Fleming, Ph.D. Arthur Levin, M.P.H.
Alex Krist, M.D. Carlar Blackman, Patient Rep.
Guest Industry Representatives
George S. Goldstein, M.D. John T. Sullivan, M.D.
Florence Houn, M.D., M.P.H. Victor Raczkowski, M.D.
Paul Seligman, M.D., M.P.H. Julie Beitz, M.D.
These summary minutes for the April 23, 2002 meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee of the Advisory Committee for Pharmaceutical Science were approved on May 8, 2002.
I certify that I attended the April 23, 2002 meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee of the Advisory Committee for Pharmaceutical Science, and that these minutes accurately reflect what transpired.
Thomas H. Perez, M.P.H., R.Ph. M. Michael Wolfe, M.D
Executive Secretary Chair
The Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee of the Advisory Committee for Pharmaceutical Science, of the Food and Drug Administration, Center for Drug Evaluation and Research met April 23, 2002 at the Holiday Inn, 8120 Wisconsin Ave., Bethesda, MD.
The Committee discussed risk management for (NDA) 21-107, Lotronex™ (alosetron), GlaxoSmithKline.
The Committee had received a briefing document from the FDA, a background package from GlaxoSmithKline, and a package containing correspondence received from members of the public.
There were approximately 300 persons in the audience. The meeting was called to order at 8:00am by the Chair, M. Michael Wolfe, M.D. The Committee members and discussants introduced themselves. Thomas H. Perez, Executive Secretary of the Gastrointestinal Drugs Advisory Committee read the Meeting Statement. A welcome and opening comments were provided by Florence Houn, M.D., M.P.H., Director, Office of Drug Evaluation III, and Paul Seligman, M.D., M.P.H., Office of Pharmacoepidemiology and Statistical Science.
GlaxoSmithKline representatives began their presentations at 8:25 a.m. and proceeded as follows.
Introduction James B.D. Palmer, M.D.
Burden of Illness & Efficacy of Alosetron Peter Traber, M.D.
Safety Assessment & Benefit Risk Overview Eric Carter, M.D., Ph.D.
Proposed Risk David Wheadon, M.D.
Management Plan Clinicianís Perspective Robert Sandler, M.D.
Summary and Conclusions James B.D. Palmer, M.D.
FDA representatives began their presentations at 10:05 a.m. and proceeded as follows.
Introduction Victor Raczkowski, M.D.
Lotronex: Clinical Trial Experience Thomas Permutt, Ph.D.
Post-Marketing Experience with Lotronex Ann Corken Mackey, R.Ph., M.P.H.
Lotronex Risk-Management Program Toni Piazza-Hepp, Pharm.D.
Risk-Benefit Issues, Summary & Conclusions Victor Raczkowski, M.D.
The Open Public Hearing included 16 participants, and began at approximately 11:30 a.m.
Sidney M. Wolfe, M.D. Public Citizen's Health Research Group
Nancy Norton International Foundation for Functional GI Disorders
Jeffrey D. Roberts Irritable Bowel Syndrome Self Help Group
Corey Miller Lotronex Action Group
Gary C. Stein, Ph.D. American Society of Health-System Pharmacists
William Brown, Esq.
Julia R. Alberino
Kathleen Kelly Ghawi
Brenda and Franklin Compton
Dennis K. Larry, Esq.
The meeting was reconvened after lunch at 1:50 p.m. with clarifying questions to the FDA and GlaxoSmithKline presentations. This was followed by an introduction to the Questions for the Committee and the Charge to the Committee given by Victor F.C. Raczkowski, M.D., Deputy Director, Office of Drug Evaluation III.
A thorough discussion of the questions followed, and the meeting was adjourned at 5:20 p.m.
The Committee discussed the following questions. The discussion will be made available through the meeting transcripts to be placed on the web when they become available.
Questions for the Committee
Vote: Yes 14 No 4
The panel generally felt that there is a need to define what are severe symptoms, what is the criteria, and what screenings are necessary to determine IBS. That patients selected for treatment be those who suffer from long term illness and exhibit a high severity and frequency of symptoms. Those most disabled appear to benefit the most. More work is needed to define, in addition to that, the subgroup of patients likely to respond substantially.
Vote: a = 0 b = 16 c = 2
The complete details of the committee member responses are recorded on the meeting transcripts to which those interested are referred.
Yes, there should be limits. As to the specific limits, the Committee provided a variety of responses. Some of the responses most frequently expressed include the following listed in order of most frequent first.
Consultation between Internist and Gastroenterologist (Book knowledge & Experience with a diagnostic algorithm type check list and possible audit of its use)
Physician with certification from some well developed and accessible credentialing program to document expertise.
Board certified Gastroenterologist with some type of CME
Restrict to Gastroenterologist for one year, appraise adverse events and relax requirement to physician plus CME approach.
The panel generally felt that this proposal was not adequate.
Vote: Inadequate 16 Abstain 2
The panel generally felt that this proposal may be useful but was not adequate. A mandatory program that is interactive (other than written) for both patients and physicians requiring correct responses seemed to be preferred.
The panel generally felt that this proposal was not adequate.
Vote: Favor Registration 13 Not in Favor 3 Abstain 2
The panel generally felt that registration should be a part of the risk management plan, and that consideration could be given to having registration as a condition of receiving drug to gather the needed information.
Generally the panel favored having a registry for certified physicians over the sticker concept. The complete details of the committee member responses are recorded on the meeting transcripts to which those interested are referred.
6. Regarding pharmacists:
GSK proposes that pharmacists accept only written prescriptions with an attached sticker. The goal is to verify in real-time that patients being dispensed Lotronex are under the care of enrolled physicians. Also, pharmacists will provide Medication Guides to patients whenever Lotronex prescriptions are filled or refilled. The goal is to provide patients with written information about the safe and effective use of Lotronex.
The panel generally felt that this proposal was not adequate. While a means of permitting pharmacists to be assured that the prescribers are certified is needed, several members voiced objections about problems and concerns they have about the inadequacy of the sticker concept as a means of communication.
7. Regarding safety outcomes:
The complete details of the committee member responses are recorded on the meeting transcripts to which those interested are referred. The Committee referred to earlier discussion that addressed this question.
Studies are needed to identify the subgroup of patients likely to benefit from the drug, so that use of the drug can be restricted to those individuals, rather than the much larger number of patients who is much less likely to benefit and in whom the risk/benefit balance is not likely to be positive.
Dr. Fleming stated that further information gathering is needed in the way of studies to determine risk. He suggested a 2 arm randomized trial to assess what sub cohort of patients that would benefit from drug treatment followed by a larger cohort study to identify an optimal drug dosing schedule. Many other study ideas emerged earlier in the day.