CORRESPONDENCE

Should the Philosophy of Postmarketing Surveillance in the US be Redefined?

With regard to the article published in Pharmaco­Economics by La Puma,[l] we would like to make some comments about postmarketing surveillance (PMS) studies. From La Puma's article, it appears that US health professionals are confused about the aim of PMS and seeding studies. However, their goals are very different.

The goals of PMS are to use epidemiological techniques to learn about the use and effects of drugs in clinical practice, and to identify previously unrecognised safety issues. In contrast, the purpose of seeding studies (or promotional activities) is to introduce and promote a new drug to physicians and patients, and in so doing to increase its sales. Seeding studies cannot be considered as scientific investigations.

La Puma states in his article[l] that little regula­tion of PMS exists in the US. However, in 1990 the American Society for Clinical Pharmacology and Therapeutics published guidelines for performing scientifically rigorous PMS studies. [2] Had the author read these guidelines, he would probably have under­stood more clearly the difference between PMS and seeding studies and he would not have con­fused their objectives.

We agree with the author that seeding studies are more concerned with marketing than with scientific research; it would therefore be unethical to pay a physician for treating a patient with a specific drug. However, we disagree with him when he states that the purpose ofPMS is uncertain. The limitations of clinical trials in obtaining information about the safety profile and effectiveness of new drugs are well known. Thus, PMS studies are essential to ob­tain data that relate to the use of drugs in daily medical practice.

PharmocoEconomics 8 (2): 175-176, 1995 11 70-7690/95/0008-0 175/S0 1 .00/0

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To be confident that PMS studies are carried out with scientific rigour and to avoid ethical contro­versies, a written protocol should be finalised that explains the aims and objectives of the study, the methods to be used and the analyses to be performed. In addition, the highest possible standards of pro­fessional conduct and confidentiality must always be maintained. Furthermore, the study protocol should be submitted to an institutional review board for appn;wal. T.his is particularly important if patients are to be approached for information, if additional investigations are to be performed or if it is intended to assign patients systematically to different treatments.

We agree that physicians should not be paid for conducting seeding studies, but PMS studies are entirely different. If we pay for clinical research (through clinical trials), why can't we pay for PMS? We think that this is unfair. Contrary to the author's point of view, we think that physicians should receive payment in compensation for the extra time that PMS entails, although no monetary incentive for a physician to take part in a such a study should be offered, promised or given. Natu­rally, the amount of these payments must be reason­able and justifiable.

At present, several countries in Europe have' promulgated some guidelines for the conduct of PMS studies in accordance with a regulation of the European Medicines Evaluation Agency.l3] We be­lieve that the US Food and Drug Administration should develop and issue some similar guidelines to clarify and regulate the conduct of these studies in the US.

lavier Soto Pharmacoepidemiology Unit

Medical Department Abbott Laboratories S.A.

Madrid, Spain

l.A. Sacristan Pharmacoepidemiology and Pharmacoeconomics

Unit, Clinical Research Department Lilly S.A.

Madrid, Spain

176

References I. La Puma J. Physician rewards for postmarketing surveillance

(seeding studies) in the US. PharmacoEconomics 1995; 7 (3): 187-90

2. Members of the ASCPT Pharmacoepidemiology Section. Notes of the American Society for Clinical Pharmacology and Ther­apeutics: position paper on the use of purported postmarket­ing drug surveillance studies for promotional purposes. Clin Pharmacol Ther 1990; 48: 598

3. Jefferys DB, Jones KH. EMEA and the new pharmaceutical procedures for Europe.Eur J Clin Pharmacol 1995; 47: 471-6

The author replies: I thank Drs Soto and Sacristan for their re­

sponse, and am grateful for their special interest in clinical ethics. I agree with the correspondents that the purpose of seeding studies is to introduce and promote drugs, ultimately increasing sales of new drugs. In contrast, the goal of postmarketing sur­veillance (PMS) is to define important, unanswered clinical or basic questions, especially those relat­ing to adverse effects, dosage or population)l)

In the US, seeding studies and PMS are one and the same, generally speaking. The vast majority of research done after a new drug is approved are seeding trials, for which physicians do not obtain informed consent but are paid, often twice. These are facts of which the US Food and Drug Admin­istration is aware,[2) and apparently would like to change.£3)

I agree that PMS should be analysed like other research. Suggestions for scientifically sound PMS have been described by Stephens;[4) ethically sound PMS is the subject of my Pharmaco­Economics editorial.[5)

Finally, 'reasonable and justifiable' compensation is a matter of perspective, and of clinical ethics. In our study of patients' and physicians' attitudes to­wafds physician remuneration for PMS,[6) we found an order of magnitude difference between what

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Correspondence

patients thought doctors should be paid, and what doctors thought they should be paid. In fact, most patients thought doctors should not be paid for PMS research at all!

The answer to the ethical dilemmas occasioned by PMS lies not in more regulation, but in stating clearly' the difference between right and wrong, and .in, making moral choices that are publicly defensible and in our patients' collective best in­terests.

Here is a prime opportunity for industry to re­store its tarnished moral credibility with the virtues of medical ethics. Courage, integrity and leader­ship - from industry and from medicine - are needed to make medications more available and more affordable to patients worldwide. Honour is a rich reward for companies willing to take a chance on scientific rigour and informed consent.

John La Puma Clinical Ethics Consultant

1945 North Burling Street, Suite lR Chicago, USA

References I. Levine RJ . Ethics and the regulation of clinical research. 2nd

ed. New Haven (CT): Yale University Press, 1988 2. Kessler DA, Rose JL, Temple RJ, et al. Therapeutic class wars

- drug promotion in a competitive marketplace. N Engl J Med 1994; 331: 1350-3

3. Kessler DA, Rose JL, Temple RJ, et al. Drug promotion. N Engl J Med 1995; 332: 1033

4. Stephens MDB. Marketing aspects of company sponsored postmarketing surveillance studies. Drug Saf 1993; 8 (I): 1-8

5. La Puma J. Physician rewards for postmarketing surveillance (seeding studies) in the US. PharmacoEconomics 1995; 7 (3): 187-90

6. La Puma J, Stocking CB, Rhoades WJ, et al. Financial ties as part of informed consent to postmarketing research: attitudes of American doctors and patients. BMJ. In press

PharmacoEconomics 8 (2) 1995