GUEST EDITORIAL I'I>oon">OCo(c"""""",,, 1 (3l I 31- 1~. 1WS 1 170-7~.olellW2 00!0

Physician Rewards for Postmarketing Surveillance (Seeding Studies) in the US johllw Puma

Department of Medicine, University of Chicago, Chicago, USA

Postmarketi ng survei llance as it is commonly understood in t he US is a lale twentieth century marketi ng strategy estimated to be worth bill ions of doll ars)IJ It is also a fasc inating and essentially unexplored area of ethical intrigue, medical collab­oration and industry necessity.

To the best of my knowledge, no published quan­

titat ive analysis, wi th the exception of a single ab­Str3Ct,t2I addresses the ethical questions about con­flic ti ng loyalties. informed consent and research purpose that poslmarkcting research raises. Little philosophica\,I31 policy-orientated,141 cl inical 151 or legal analysisl61 is available. Because most surveil­lance is cond ucted outside of academic institu­tions, the interplay of its goals, methods and results have generally not yet attracted the attention of US scholars and acade micians. Unli ke the UK's quad­ripartite guidclines,l7! little regulation of postmarket­ing surveillance ex ists in the US, allowing an open

speCUlative frontier for entrepreneurs to shape and settle.

Here , I will briefl y describe the goals and set­tings of postmarketing surveillance and the ethical di lemmas it presents for clinicians, including fi­nancial conflicts of inte rest. 18/ Ultimately, [ will try to answe r the question: should pharmaceutical companies ease price control pressure by foregoi ng rewards for physicians who perform postmarketi ng surveillance?

1. Goals and Practices of Postmarketing Surveillance Research in the US

There arc two common yet confiicting goals of postmarketing surveillance research: (i) to define important, u nanswcred cl inical or basic questions, espec ial ly those pertain ing to adverse e ffects, safety, dosage or popu!ation;191 and (i i) to familiar­ise physicians and patients wi th the names and uses of new, approved drugS. IIOI Studies that have the former goal, known to the US Food and Drug Administrati on (FDA) as 'commitments', may also have secondary marketing purposes,!1I1 and these studies com prise a small minority of post markel­ing research. In the US, Ihe vast majority of postrnarketi ng surveillance is intended 10 promote product familiari ty. and is the subject of this analysis .

In the US, investigators engaged in postmarket­ing surveillance arc Iypically private physicians, pract ising in outpatient office sett ings. Industry sponsors typically approach physicians directly, offering drug samples, office visit allowances, lab­oratory work payments and per capita enrolment fees for the successful enrolment of patients in whom. for example, their new nonsteroida l anti­infiammatory drug is indicated.

In turn, physicians enrol their patients, or (upon referral) those of their colleagues. complete the necessary paperwork and laboratory tests, and pre-

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scribe the sponsor 's drug. Patients do not usually have to pay for their tests. medications or office visits. Informed consent may be oblai ned from the patient and an institutional review board may re­view the study. but these e(hics measures arc the exception. not the rule.

Unlike any other type of medical research, phy­sicians and patients engaged in postmarketing sur­vei llance can reasonably ex pect personal medical benefit. as the medicat ion has been approved by the US FDA for the treatment of the patient'S medical condi tion. Also unlike any other type of medical research, physicians can be paid twice (by the pa­tient's insurer and by the industry sponsor) for a single action. as a doctor and invest igator. Many physicians are unaware of the actual promotional goal of such research. and believe that they are be­ing paid for their data.

2. Ethical Dilemmas

For a physician who participates in suc h a familiarising, survei llance or seed ing study, the fu ndamental ethical issues arc those of dual loyalty, pat ient advocacy, research purpose, informed con­sent and accountability.

Distinct concerns about IOYility exist for the postmarketing surveillance investigator, who must be physician, researcher and promoter at the same time. Using one FDA-approved medication, there are at least 2 different goals: (i) enhancing a pa­tient's well-being; and (ii) gathering generali sed knowledge for fut ure patients, as utili sed by the drug company sponsor. Owing allegiance to the pa­tient on the one hand, and to the sponsor's market­ing effort on the other. may make for an unsuitable prescription.

The issues of dual loyalty and patient advocacy are compounded if a physician enrols his or her own patient. Incentives 10 prescribe a medication that may yield an enrolment bonus for the physician and free medication for the patient make such an ar­rangement almost irresistible to both, yet clear to neither. How much the physician is paid if the pa­tient volunteers 10 participate is seldom disclosed.

C> Adis Int&moIiOoal Umited. Ai riglls 'eseNed

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Advocacy for patients as a whole may also suf­fer when a physic ian is paid for post marketi ng s ur­veillance. as all patients mu st ultimately pick up the cost of the doctor's postmarketing surveillance

fee in higher medication costs. If patients know that the goal s of seeding studies arc promotional. they will at the very least want to know for whom is the physician working.

Research purpose is uncertain for post market­ing surveillance. Participating physician investiga· tors may have special difficulty di stinguishing be­tween research and therapy. and between research and marketi ng. Asking several questions can help elucidate these differences. What is the study'S hy­pothesis? Is there an available research protocol?

Did an institutional rev iew board approve the study? Did the patient give informed consent to part icipate in the research? In seeding studi es, a nu ll hypothesis is often absent and the answers to the other questions are usually all 'no'.

Informed consent normally includes under­standing and appreciat ing ri sks and benefit s. In this case. the ri sks and benefits of the FDA- approved medication arc spe lled out in thi s year's Physi· cian s Desk Reference or are otherw ise available on the Internet. However, do the answers to questions about a physician's loyalty represent a risk of ther­apy? Could an investigator's financia l ties to a re­search sponsor benefit the patient in any way? If fi nancial interests do not influence the investiga­tor 's medical judgement, are they a moral risk?t 121

Do patie nts participating in research trials need to know their physician-investigator 's stock owner­ship, fees and consultancics to make an informed, in­dependent decision whether to enter a drug study?

A few professional organisations have been con­cerned with an accounlabi lity in research that may not have appeared problematic to researchers. The

Canadian Royal College of Physicians. for exam­ple, advocates that the source of fu nding for any research project be disclosed t o patients, and dis­courages physicians from accepting per capita pay­ments for enrolment or any other remuneration from industry sponsors.l 131

Physician Rewards for Postmarketing Surveillance

Vet, as a matter of integri ty and public presence, industry may not wish to wait unti l t he US medical profession catches on.l t41 Industry may wish to forego the pract ice of offering remuneration 10 physicians for performing postmarket ing sur­veillance.

3. Five Reasons Why Industry Should Forego Physician Rewards for Postmarketing Surveillance

First, the practice of paying physicians to per­form seedi ng studies is inconsistent with industry's mission as a moral entity. Seeding studies arc ac­tually more concerned with marketi ng than they are with scienti fic assessment. Thus. paying phy­sic ians to promote new drugs through seeding studies whi le not disclosing these arrangements 10 patie nt s undermines company integrity and the pub lic's expectation of honesty.

Secondly. eve n physician disclosure of their connict of interest will likely be insufficient to re­solve thei r dual loyalt ies. Many physicians will be uncomfortable and uncertain about what 10 say. Most i ndividual abuses arc unlikely 10 be vast. but physician misunderstanding and misinformat ion about the goals and objectives of most survei llance probably is.

Thi rdly, if physician rewards for post marketing activities were foregone. the monies made avail­able could be diverted to research and development of products designed to meet important, unmet clinical needs. thereby reducing the number of duplicative drugs produced and promoted.

Fourth ly, wi thout the physic ian fee, industry wi ll be more able 10 appeal 10 consumers more di ­rectly. Marketing products directl y to consumers should remove the physician middleman and re­ducc consumer costs, resulting in increased sales. While this solution may only be applicable where prescription products can be marketed directl y to the consumer, overall costs will sti ll decl ine and companies will be able to defray the cost of medi ­cations. Industry will have consu mers on its side.

Finally, as more patients enter managed care or­gani sations, industry's pharmacy benefit managers

e AdillntelOo!lonal lh'"liTe<l. AJ riQhTs rewlVe<l.

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wi ll look fo r other ways to make deals with health plan s. Few managed care formulary groups will stock dupl icative drugs. Fewer managed care health plan counsels will look happily upon poten­tial plan li ability for physicians who are paid twice, without informed consent, for promoting a spon­sor's drugs. Yet, many counsels might help spon­sors place greater effort on the scientifically legit­imate goals of post marketing surveillance. The search for answers to scientific questions about un­met clinical needs might help justify an institu­tion's tax-exempt status, and lead 10 a new, scien­tific role for post market ing research.

4. Conclusion

Once the magnitude and scope of industry seed­ing studies in the US is better known, 1/01 disclos­ing investigator compensation is likely to be per­ceived as secrecy in research. Nondisclosure may also be perceived as more evide nce that phys icians are eager to be eve n better paid than they already are.

Both concl usions are avoidable. Courage, in­tegrity and leadership fro m bot h indu stry and medicine representatives are needed to make med ­ications more avai lable and more affordable to

patients. Identi fying the ethical d ilemmas involved in survei ll ance research is a first step in that di­rection.

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Correspondence and reprints: Dr Joh/! Ut PIII1Ul, ]945 North Burling Street, Suite IR.Chicago, IL60614, USA.