Report of the Harvard Program in Pharmacoepidemiology

1994-1995 School Year

Alexander M. Walker, M.D., Dr.P.H.
Professor of Epidemiology and Director of the Program
September 1995


Contents


Introduction

We are using our funds to train top flight practitioners who have expertise in the special problems posed by drugs, vaccines, and medical devices, and who are as comfortable working in industry and regulatory agencies as they are in academia.

Doctoral Student Training

Doctoral students this year pursued substantive and methodological research on drug effects on the epidemiology of diseases that are new candidates for drug therapy. These are the current doctoral candidates:

Master's Degree Students

Beginning last year, we decided to add an emphasis on the training of Master's degree candidates to the program. One student was admitted last year, and two are entering this fall. Last year Master's degree recipient, Vera Mastey is a Canadian with a PharmD who wanted to branch into outcomes research. She has gone on to join Pfizer, where she is working in international outcomes research. This year's students are Miriam Sturkenboom, a Dutch researcher who has been studying population determinants of acitretin metabolism, pregnancy outcomes in acitretin users, and other effects associated with drug. She has come for a year of in depth formal training. Chris Kahler is an American hospital pharmacist who is here because he wants to enter industry with a pharmacoepidemiologic background. Christoph Maier is a Swiss clinical pharmacologist who has specialized in drug information systems for physicians will pursue a part-time course while working with Hershel Jick at the Boston Collaborative Drug Surveillance Program.

Affiliated Students

A number of students who are not formally part of the pharmacoepidemiology program have taken advantage of the training we offer to prepare themselves for pharmaceutical careers. Paul Coplan, graduated in June from the psychiatric epidemiology program and went on to join Harry Guess's epidemiology and safety group at Merck. Current doctoral students Loren Lipworth and Edmond Shenassa are working closely with a manufacturer in the analysis of observational data in support of licensing applications for a vaccine. As such they have the opportunity to work closely with industry colleagues, and to see the workings of the FDA at close range. Christine Huttin is a French economist who spent the year in Harvard's Takemi Program in International Health. In collaboration with Jerry Avorn and with assistance from me she has been improving her epidemiologic skills, and has developed an empirical test of a cost model for hypertension, using French reimbursement data. Marshall Joffe is a post-doctoral student who has begun to apply mathematical techniques that tease out the cycle of disease manifestation predicting drug use, which affects disease manifestation. He and I will be working closely together in the 1995-1996 school year.

Other Faculty

Harvard faculty members contributing to the research program and to the supervision of students this past year included Richard Platt of Harvard Community Health Plan, Jerry Avorn at Harvard Medical School, and Malcolm Maclure, who shares his time between HSPH and the Province of British Columbia. Hershel Jick and Susan Jick of the Boston Collaborative Drug Surveillance Program (Boston University) offer ongoing collaborations to a number of students.

Research Sites

Students and faculty associated with the program have pursued their research activities in a wide variety of settings in the past year. These include two staff model HMOs in Massachusetts, a general practice data base, and three governmental units:

Outreach

The pharmacoepidemiology course and the pharmacoepidemiology seminar series provide our major activities within the larger Harvard community. The course this year had 14 students, nearly all of them physicians or pharmacists, most with current research interests in drug safety, drug effects or drug economics. The seminar series, coordinated by Karin Michels, D.Sc. while she finished her dissertation on effects of diethylstilbesterol, included speakers from industry, the FDA, academia, and law. I have appended a list of topics and speakers to this letter.

Outreach beyond the Harvard community has included a new venture in electronic publishing on the World Wide Web and a major service commitment to the International Society for Pharmacoepidemiology (ISPE). Our Web site, the Drugs and Devices Information Line (http://www.hsph.harvard.edu/Organizations/DDIL/ddilhpge.html) contains review articles written by students and by me, and offers connections to other sites of interest in drug epidemiology. I have attached a copy of the DDIL home page.

At ISPE, I have the honor of serving as President for the 1995-1996 year. The greatest achievement of the Society has been to provide a collegial forum where members of our profession can meet colleagues unhindered by the usual division into academic, industry, and regulatory worlds. The recently completed annual congress in Montréal attracted 525 registrants, and was perhaps the best to date in terms of science and interaction. Next year's congress will be held in Amsterdam. In the year between congresses, the Society is working on issues vital to the field. The Public Policy and Ethics Committee is dealing with the implications of European confidentiality guidelines for large data base research, and members are involved in shaping national guidelines. I have written two articles in support of this effort in the Society's journal, Pharmacoepidemiology and Drug Safety. The Guidelines committee, consisting of members from the FDA, Pharma, and academics within the Society (including Harvard faculty Jerry Avorn and myself) has developed standards for the documentation and conduct of pharmacoepidemiologic studies. The document responds to a challenge set before the Society by the FDA's Robert Temple at our congress in Washington two years ago. (You can find this document and other on the DDIL home page.)

Sponsors

We are deeply grateful for major support this past year from Berlex, Boehringer-Ingelheim, Ciba Geigy, Hoffman La Roche, Merck, and Pfizer. Connaught Laboratories has recently indicated that it wishes to join the group of sponsors, and I am in discussion with several other companies. Representatives from sponsoring companies commonly visit the School to attend or offer seminars, and to meet with students. I am always available to sponsors to offer advice and help where I can, and to help them arrange for longer term consulting and research projects.

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Pharmacoepidemiology Seminars and Speakers, 1994-1995


Drug Utilization

Compliance with Medications
Mark Monane, MD
Harvard Medical School

Drug Safety

Can a Human Teratogen be Used With Relative Safety? The Case of Accutane
Allen Mitchell, MD
Boston University
A Nationwide Clinical Trial of Ibuprofen Use in Children
Samuel Lesko, MD
Boston University

Regulatory Issues

The Use of Adverse Drug Reaction Reports by the FDA
Peter Barton Hutt, Esq.
Covington & Burling
Appropriate Use of Placebo-Controlled Studies
Robert Temple, MD
Food and Drug Administration
The Evolution and Philosophy of FDA Safety Regulations: Epidemiologic Implications
Gerald Faich, MD, MPH
Pharmaceutical Safety Assessment, Inc.

Methods and Data Resources

Confidentiality Restrictions on the Use of Large, Linked, Data Bases
Alec Walker
Layered Cohort Designs for Drug Utilization Epidemiology
Malcolm Maclure, ScD
Harvard School of Public Health
Desktop Manipulation of Large Health Care Databases
Susan Andrade, DSc
University of Rhode Island, and
Alec Walker
Denmark: A Sleeping Beauty for Pharmacoepidemiologists?
David Gaist, MD
Odense University

Outcomes

The Inter-relationship of Epidemiology, Outcomes Research, Disease Management, and Related Topics in Healthcare Research
Bruce J.O. Wong, MD
SmithKline Beecham

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Publications 1994-1995


  1. Chan KW, Felson DT, Yood RA, Walker AM. Incidence of rheumatoid arthritis in Central Massachusetts. Arth Rheum 1994:36:1691-1696
  2. Fontanet AL, Johnston BD, Walker AM, Bergqvist Y, Hellgren H, Rooney. Falciparum malaria in eastern Thailand: a randomized trial of the efficacy of a single dose of mefloquine. Bull WHO 1994;72:73-78
  3. Chan KW, Felson DT, Yood RA, Walker AM. The lag-time between onset of symptoms and diagnosis of rheumatoid arthritis. Arth Rheum 1994;37:814-820
  4. Traversa G, Caracciolo B, Da Cas R, Menniti Ippolito F, Raschetti R, Walker AM. L'uso dei farmaci antinfiammatori nonsteroidei nella popolazione di Roma. Giornale Italiano di Farmacia Clinica 1994;8
  5. Gray DT, Walker AM, Fyler DC, Chalmers TC. Examination of the early "learning curve" for transcatheter closure of patent ductus arteriosus. Circulation 1994;90[part 2]:II36 - II42
  6. Walker AM, Bortnichak EA, Lanza LL, Yood RL. The infrequency of liver function testing in NSAID users. Arch Fam Med 1995;4:24-29
  7. Traversa G, Walker AM, Menniti Ippolito F, Caffari B, Capurso L, Dezzi A, Koch M, Maggini M, Spila Alegiani S, Raschetti R. Gastroduodenal toxicity of different NSAIDs: a case-control study in the Province of Rome. Epidemiology 1995;6:49-54
  8. Zuber PLF, Jacquier P, Hohlfeld P, Walker AM. Toxoplasma infections among pregnant women in Switzerland: a cross-sectional evaluation of regional and age-specific lifetime average annual incidence. Am J Epidemiol 1995;141:659-666
  9. Walker AM. IMBRF/ISPE conference on medical databases and privacy. (Commentary) Pharmacoepidemiol Drug Safety 1995;4:15-16
  10. Andrade SE, Walker AM, Platt R, Hollenberg NK, Testa MA, Saperia GM, Gottlieb LK. Discontinuation of antihyperlipidemic drugs: Do rates reported in clinical trials predict rates in primary care settings? N Engl J Med 1995;332:1125-1131
  11. Walker AM. Low power and striking results -- A surprise but not a paradox. (editorial) N Engl J Med 1995;332:1091-1092
  12. Avorn J, Bohn RL, Mogun H, Gurwitz GH, Monane M, Everitt D, Walker AM. Neuroleptic drug exposure and treatment of parkinsonism in the elderly. Am J Med 1995;99:48-54
  13. Lanza LL, Walker AM, Bortnichak EA, Gause GO, Dreyer NA. Incidence of symptomatic liver function abnormalities in a cohort of NSAID users. Pharmacoepidemiol Drug Safety 1995;4:231-238
  14. Lanza LL, Dreyer NA, Schultz NJ, Walker AM. Use of insurance claims in epidemiologic research: Identification of peptic ulcers, GI bleeding, pancreatitis, hepatitis and renal disease. Pharmacoepidemiol Drug Safety. 1995;4:239-248
  15. Oliveria SA, Felson DT, Reed JI, Cirillo PA, Walker AM. The incidence of symptomatic hand, hip and knee osteoarthritis in a health maintenance organization. Arthritis Rheum 1995;38:1134-1141
  16. Lanza LL, Walker AM, Bortnichak E, Dreyer NA. Peptic ulcer and gastrointestinal hemorrhage associated with NSAID use in patients under 65 years of age. Arch Int Med 1995;(in press)
  17. Hayashi K, Walker AM. Japanese and American reports of randomized trials: Differences in the reporting of adverse effects. Contr Clin Trials 1995; (in press)
  18. Walker AM. Generic data. Pharmacoepidemiol Drug Safety. 1995;(in press)
  19. Andrade SE, Saperia GM, Gottlieb LK, Walker AM, Platt R. Effects of gender and age on the discontinuation rate of antihyperlipidemic drug therapy. (submitted)
  20. Andrade SE, Platt R, Gottlieb LK, Saperia GM, Walker AM. Discontinuation of drug therapy: Assessment by means of automated data bases. (submitted)
  21. Oliveria SA, Felson DT, Klein RA, Reed JI, Walker AM. Estrogen replacement therapy and the development of osteoarthritis. (submitted)

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