Below you’ll find a thought-provoking and informative editorial from the March 30 issue of the New England Journal of Medicine. The author is Professor of Medicine at Harvard Medical School and Chief of the Division of Pharmacoepidemiology and Pharmacoeconomics. He asks, but only begins to answer, the fundamental question above. Below are 2 quotes from the piece that should intrigue you enough to want to read on. At the editorial’s conclusion, you’ll find a hyperlink to a 1-minute-and-20-second excerpt from Dr. Avorn’s lecture on this topic at Harvard Business School.
“The evidence base available to clinicians to guide their therapeutic choices is still heavily shaped by industry-sponsored studies that often compare new products with placebo, measure their worth in terms of surrogate markers such as laboratory test results, or both.”
“They [package inserts] live on as tangled obfuscations filled with minimally usable data and liability-averting warnings.”
Teaching Clinicians about Drugs — 50 Years Later, Whose Job Is It?
NEJM | March 30, 2011 | Topics: Drugs, Devices, and the FDA
Jerry Avorn, M.D.
This year marks the 50th anniversary of the Kefauver hearings, the pivotal 1961 Senate debate that transformed prescription drug approval and use. When Senator Estes Kefauver (D-TN) introduced legislation to regulate the drug industry, the Food and Drug Administration (FDA) still did not have legal authority to require pharmaceutical companies to demonstrate that their products actually worked. What physicians knew about prescription drugs was shaped predominantly by the claims their manufacturers made about them, and the evidence base underlying such claims was often rudimentary, or worse.
Closely related to the thinness of the science was the question of how information about a drug’s benefits and risks should be evaluated and communicated to physicians — and by whom. Then as now, pharmaceutical companies mounted aggressive promotional campaigns for their products. An unsigned 1961 Journal editorial titled “Ethical Drugs — Who Shall Educate the Physician?” noted with concern that “manufacturers spend about four times as much on the promotion of drugs as the total cost of running all the medical schools.” As a result, the editorial continued, “the majority of physicians get their first and often their only information about newly available drugs from these sources, which at best may be strongly prejudiced and at their worst are unreliable and misleading.”1 No mechanism existed for robust, arm’s-length governmental determination of a drug’s efficacy and for the dissemination of such data — a solution that many clinicians did not favor in any case. As a result, practitioners were often left with little disinterested guidance about the usefulness or safety of new medications in comparison with their alternatives.
Among other things, the Kefauver legislation sought to have the federal government provide a more even-handed, public source of drug education for physicians: a leaflet that would accompany every prescription medication describing “all the information about the activity, uses, and untoward effects of the drug”; a compendium of such information for all products “in convenient and readable form” to be distributed widely; and an annual list of medications with high potential for serious side effects.
The American Medical Association (AMA), skeptical about any public-sector role in health care, argued that this was not a proper activity for government and that such communication should be the responsibility of the profession itself, along with industry. The AMA had been attempting to fill this function through its Council on Drugs, a group of researchers and clinicians that evaluated new medications and issued a “Seal of Acceptance” to those meeting its standards. Only drugs thus accepted could be advertised in the AMA’s journals.2 However, NEJM‘s editorialist lamented in 1961 that the AMA had largely dismantled these programs, a decision that led to “encouraging the introduction of relatively inferior drugs . . . [and] the deterioration in the quality of advertising and promoting such drugs. These changes have done little to help but may have done much to confuse the physician in his efforts to practice good medicine.” The Journal noted that this failure undercut the AMA position that a governmental program was not needed.
The pharmaceutical industry and the AMA attacked Kefauver’s bill, and the idea that the government should play a central role in evaluating medications for efficacy and disseminating information about them seemed headed to legislative defeat. Then came the thalidomide disaster. That drug was being heavily promoted in Europe as a sedative and antinauseant, particularly for use during pregnancy, but a more cautious FDA approach had spared Americans the epidemic of fetal limb-reduction defects that plagued countries with more permissive drug regulatory systems. Empowered by this crisis, the Kefauver hearings resulted in a new law that gave the FDA the authority to require evidence of efficacy and safety before a drug could be marketed.3 The debates about disseminating drug information eventually led to the now-familiar “package inserts” that fit the law’s requirement for completeness, even if they have still not lived up to its larger goals of usability and readability.
Half a century later, the editorial’s question, “Who shall educate the physician?” is still hotly contested. Opposition to a role for government did not carry the day then but has dominated debate ever since; the letter of Kefauver’s legislation about drug information has been followed in one narrow sense, though its spirit has not fared as well. The evidence base available to clinicians to guide their therapeutic choices is still heavily shaped by industry-sponsored studies that often compare new products with placebo, measure their worth in terms of surrogate markers such as laboratory test results, or both.
The recent comparative effectiveness movement holds great promise for improving this evidence base, if it survives politically. Package inserts have been legally mandated, but until recently their content was determined primarily by the manufacturer, not the FDA. They live on as tangled obfuscations filled with minimally usable data and liability-averting warnings. Proposals for improving them are floated periodically, and 2007 legislation may give the agency more power to address this problem. But for the most part, the 1961 vision of an unbiased, user-friendly, practical summary of benefits and risks produced by the government for each prescription drug has not come to pass.
On the education front, recent reforms have only partially addressed concerns about the undue influence of drug companies on what physicians know (or think we know) about medications, mediated through aggressive promotion, less visible and more indirect public relations campaigns, and a manufacturer-dominated continuing medical education industry. The 1961 editorial’s reference to “ethical drugs” — an old term for prescription medications — seems oddly archaic in a time of scandals about deceptive marketing practices and heavily advertised, costly medications that turn out to have major unreported risks.
One positive response to the editorial’s question has been the outreach activities that have evolved to disseminate noncommercial drug information to clinicians. The Agency for Healthcare Research and Quality (AHRQ) has long tried to provide a public-sector source of evidence-based information on drugs and other interventions. It initially did its job so effectively that in the mid-1990s it was nearly defunded after pressure was exerted by advocates for treatments that were more lucrative than effective.4 A chastened AHRQ has remained engaged in this area but is reluctant to issue therapeutic guidelines that could again threaten its existence.
As the United States turns away from 1960s-era belief about government’s role in protecting the public health, and as concern grows about industry’s influence on federal policy positions, the answer to who shall educate the physician is increasingly unlikely to be “Uncle Sam.” Instead, an emerging answer may be public–nonprofit collaborations for which the government provides funding but profession-based nongovernmental entities with no ties to industry generate the scientific content. One illustration is the growth of support for “academic detailing” — educational outreach programs in which independent researchers and clinicians systematically review data for a given therapeutic area and develop noncommercial, evidence-based recommendations about treatment choices. Pharmacists, nurses, and physicians are then sent to visit practitioners in their offices to present these findings, drawing on the successful marketing strategies of industry but without its sales-oriented spin.5 Several states, insurers, and federal programs currently fund academic detailing programs based on content developed by nonprofit organizations free of industry ties. As concerns grow about the safety, complexity, and affordability of our expanding pharmacopoeia, demand for these programs increases.
Fifty years after the Journal grappled with these issues, they are even more relevant, and the need to provide reliable drug information to physicians is even more pressing. Enlightened by our tumultuous experience with medications and drug communications over the past half-century, we are still working on a sustainable answer to this question that lies at the heart of medical practice.
From Harvard Medical School and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital — both in Boston.
1. Ethical drugs — who shall educate the physician? N Engl J Med 1961;265:910-912
2. Greene JA, Podolsky SH. Keeping modern in medicine: pharmaceutical promotion and physician education in postwar America. Bull Hist Med 2009;83:331-377
3. Carpenter D. Reputation and power: organizational image and pharmaceutical regulation at the FDA. Princeton, NJ: Princeton University Press, 2010.
4. Gray BH, Gusmano MK, Collins SR. AHCPR and the changing politics of health services research. Health Aff (Millwood)2003;W3-283-W3-307
5. Avorn J. Devising an antidote. In: Avorn J. Powerful medicines: the benefits, risks, and costs of prescription drugs. New York: Alfred A. Knopf, 2005:313-38.
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