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.” {This 1961 article is not available on line--jk}. 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.
Drug Ads That Appeared in the Journal in
1961 for an Amphetamine, a Monoamine Oxidase Inhibitor, and an Anabolic Steroid.
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
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. {This is now a sham written by the manufacturer with bias, not reviewed
by the FDA, and printed in small type to discourage its being read}.
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 (see www.RxFacts.org). 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.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
Source Information
From Harvard Medical School and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine,
Brigham and Women’s Hospital — both in Boston.
References
- Ethical drugs — who shall educate
the physician? N Engl J Med 1961;265:910-912
Full Text | Web of Science
- Greene JA, Podolsky SH. Keeping modern in medicine: pharmaceutical promotion and physician education
in postwar America. Bull Hist Med 2009;83:331-377
CrossRef | Web of Science | Medline
- Carpenter D. Reputation and power: organizational image and pharmaceutical regulation at the
FDA. Princeton, NJ: Princeton University Press, 2010.
- Gray BH, Gusmano MK, Collins SR. AHCPR and the changing politics of health services research.
Health Aff (Millwood)2003;W3-283-W3-307
- 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.
