Second Opinion:
Where health policy experts have their say

March 17, 2008: Off-Labeling Marketing

Recent headlines have cast doubt on the FDA's draft proposal (available here) to allow "off-label marketing": the dissemination by pharmaceutical companies of peer-reviewed journal articles on prescription drug treatments beyond those indicated on FDA-approved labels.

We sent the following news story, Doctors divided over marketing by drugmakers (Newark Star-Ledger, 3/03/08) to leading health care scholars and asked: Should drug companies have the latitude to inform doctors about off-label uses of their products?

This week's panel includes:

• Richard A. Epstein is the James Parker Hall Distinguished Service Professor of Law at the University of Chicago, a Senior Fellow of the Center for Clinical Medical Ethics at the University of Chicago Medical School, and the Peter and Kirstin Bedford Senior Fellow at the Hoover Institution. His most recent book on health care is Overdosed (Yale University Press). (Read Epstein's Second Opinion.)
• Paul Howard is a senior fellow at the Manhattan Institute's Center for Medical Progress and the managing editor of MedicalProgressToday.com. More writing by Paul Howard can be found here. (Read Howard's Second Opinion.)
• Gilbert Ross, M.D. is the Executive and Medical Director at The American Council on Science and Health. For more information, please visit www.acsh.org and www.healthfactsandfears.com. (Read Ross's Second Opinion.)
• Thomas P. Stossel, M.D. is Director of the Division of Translational Medicine at Brigham & Women's Hospital, American Cancer Society Professor of Medicine at Harvard Medical School, and a senior fellow at the Manhattan Institute's Center for Medical Progress. (Read Stossel's Second Opinion.)
• Benjamin Zycher is an economist and a senior fellow at the Manhattan Institute's Center for Medical Progress. Find op-eds and studies by Zycher here. (Read Zycher's Second Opinion.)

"The FDA should facilitate and encourage the active collection of information about off-label uses from drug companies and from anyone else, including many independent third parties, who is able to gather the information. It is not commonly understood that in many areas, like cancer treatment, off-label uses dominate.

The FDA position that doctors may use but drug companies not promote leads to the systematic undercollection of information. That absence of information can have serious bad consequences if news of adverse events is not disclosed or if news of good outcomes are slow to reach the marketplace. The issue in this case is not how to preserve the FDA monopoly over drug approval, but how to weaken it. The ever lengthening time required for clinical trials means that more new medical developments will come from new uses of established treatments. Full information is an FDA mantra generally. It should be the FDA practice here."

—Richard A. Epstein is the James Parker Hall Distinguished Service Professor of Law at the University of Chicago, a Senior Fellow of the Center for Clinical Medical Ethics at the University of Chicago Medical School, and the Peter and Kirstin Bedford Senior Fellow at the Hoover Institution. His most recent book on health care is Overdosed (Yale University Press).

"What we know about drugs when they are approved by the FDA is often only a fraction of the knowledge that will emerge in the years and decades of research and patient experience that follow. Faster diffusion of reliable information on off-label drug use will improve drug safety and efficacy, an outcome that both FDA and Congress should encourage. FDA's proposal that companies should be able to explicitly distribute research from peer-reviewed journals is a welcome, common-sense step in that direction."

—Paul Howard is a senior fellow at the Manhattan Institute's Center for Medical Progress and the managing editor of MedicalProgressToday.com. More writing by Paul Howard can be found here.

"Doctors are, in fact, not divided over drug company marketing. Most doctors who actually practice medicine-as opposed to "watchdog" group employees and the regulators in Washington-appreciate receiving insights from any source about new drugs and beneficial new applications for older ones.

As for the complaint that these studies are "funded by the drug companies"--isn't it enough that an article goes through peer-review, plus ubiquitous "full disclosure" addenda, to allow intelligent, conscientious physicians to make a reasoned decision about utilizing the data in such articles—no matter who provides it? Of course, a thorough informed consent discussion with the patient must also occur-with off-label use as with approved indications.

Demanding that all new applications go through the FDA approval process fails to recognize that that process can take up to a decade; meanwhile, patients will suffer and die for lack of treatment which might be known to be effective-or even standard of care. As for safety, off-label use can cause serious adverse reactions-just as approved uses can. Nothing is 100% safe, and all drugs should be prescribed with that in mind.

And I haven't even mentioned the Constitutional rights of drug companies to practice free speech."

—Gilbert Ross, M.D. is the Executive and Medical Director at The American Council on Science and Health. For more information, please visit www.acsh.org and www.healthfactsandfears.com.

"The off label use of medical products based on published evidence is not only perfectly legal but is prevalent, especially in cancer management. It is mind-boggling to contemplate the delays in introduction of innovations, not to mention the expense, which a requirement to demand FDA approval of every new intervention in the diverse fields of medicine would impose. The JAMA editor's dislike of unapproved treatments justified by peer-reviewed journal articles seems inconsistent with JAMA practice. JAMA sells a glossy package of reprints of its articles for promotional purposes of company sales reps, and the advertisement for this service contains no disclaimer regarding label or off-label use."

—Thomas P. Stossel, M.D. is Director of the Division of Translational Medicine at Brigham & Women's Hospital, American Cancer Society Professor of Medicine at Harvard Medical School, and a senior fellow at the Manhattan Institute's Center for Medical Progress.

"Truthful information is virtuous, and more is better than less, notwithstanding the incentives of bureaucrats, policymakers, and the various species of self-promoting advocates to enhance their own authority at the expense of doctors and patients. Forget the usual public posturing about FDA statistical protocols and double-blind gold standards: No one actually believes that FDA pronouncements from the Beltway mountaintop are the last word on safety and efficacy issues, even in the aggregate, let alone for any given patient. And let us not be fooled into thinking that an all-wise and all-knowing federal government somehow has rewritten the timeless process by which technological advance has been achieved over millennia: trial and error from the bottom up.

Patients and their doctors know their individual conditions and needs far better than do faraway armies of nameless and faceless regulators. That is why there exists an enormous gray market in off-label drug use, engendered by a decentralized information system far more supple than the regimented box-checking of the FDA.

And so Yes, emphatically: Let the drug companies offer truthful information in competition with one another, and let doctors and patients decide which treatment paths to pursue and which risks to accept."

—Benjamin Zycher is an economist and a senior fellow at the Manhattan Institute's Center for Medical Progress. Find op-eds and studies by Zycher here.