Patients Protest Promiscuous Promotion of Off-Label Prescribing

A coalition of consumer groups later today will send a scathing letter to the Food and Drug Administration protesting a proposal to give manufacturers a blank check to promote the off-label use of drugs and devices. The letter, signed by Consumers Union, the Center for Science in the Public Interest, the Government Accountability Project and a half dozen other patient and consumer groups, charges the lenient guidelines will undermine the FDA's authority to regulate off-label marketing and lower incentives for firms to conduct rigorous clinical trials or seek agency approval for the uses to which the drugs are being put.

The guidelines mark a "180-degree reversal of prior practice (by) eliminating Food and Drug Administration review of articles that manufacturers plan to distribute to physicians. As a weak and dangerous alternative, the draft guidance proposes a de minimus self-regulating standard," the letter asserts.

Under the proposal, the only requirements on articles distributed to physicians in their offices by drug industry salesmen is that they come from peer-reviewed journals that have a conflict-of-interest disclosure policy and that they be "well-controlled," which is not defined in the draft guidance. The guidelines would not protect against distribution of ghost-written articles, such as the dozens of studies funded and written by Merck scientists that later appeared in journals under academic physicians' names. Nor would they protect against the mass distribution of so-called seeding studies, which, while peer-reviewed, often are of limited size and do not have statistical significance.

The guidance does not require that the distributed studies reflect the traditional and scientifically valid gold standard of medical research—randomized controlled clinical trials. Despite the best interests of medical research and patient safety, an increasing number of studies that appear in peer-reviewed literature are small in size, without a randomized control arm, or contain an inappropriate control arm (placebo instead of an approved use for that indication). Far too many studies are of limited or even insignificant statistical validity. Indeed, the proliferation of such studies in journals has become so prevalent that one former medical journal editor, Richard Smith of the British Medical Journal, branded medical journals “an extension of the marketing arms of pharmaceutical companies.”

The proposed guidance's conflict-of-interest rule is totally inadequate, the letter noted.

Journal conflict of interest policies are routinely violated by researchers and disclosure offers no protection against ghost-writing by industry paid consultants. Merck had dozens of ghostwritten articles drafted for its infamous pain-reliever Vioxx, according to a recent Journal of the American Medical Association article. Furthermore, what constitutes the weight of credible evidence is itself a contested terrain, with industry underwriting the creation of many evidence reviews and clinical practice guidelines.

"The proposed guidance would allow industry salespersons to distribute literature that industry has largely created under controls that industry has largely underwritten," the letter noted. "The FDA proposed guidance would be in effect a de facto deregulation of the nation’s medical information distribution system that would endanger patient safety."

One in five prescriptions in the U.S. (21 percent) are for uses not approved by the FDA. The majority of these unapproved uses (73 percent) lack any evidence or rigorous studies to support the safety and efficacy for that use, according to the letter.

Historically, the FDA not only reviewed literature distributed by manufacturers to physicians that described off-label use, but limited manufacturers to distributing articles for uses where the companies were at least seeking regulatory approval by running randomized controlled clinical trials -- the gold standard of medical research. The proposed guidance would sharply reduce incentives for manufacturers to complete such trials.

"When manufacturers can market drugs and devices with journal articles, they have an incentive to set up trials with endpoints designed to make their products look good, not meet regulatory standards," the letter stated. "Compared to the FDA approval process, the publication process makes it easier for pharmaceutical and medical device companies to hide information about the shortcomings or risks of their products. Companies will take advantage of the opportunity to delay publication of results they don’t like, as illustrated, for example, by the failure of companies to timely release risk and effectiveness information about Vytorin, Avandia, and Vioxx."

Individuals can issue their own protests before the Monday deadline by going to Regulations.gov and putting the docket number FDA-2008-D-0053 in the search field under the "Comment or Submission" tab. That will take you to “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices,” where you can hit the "submit a comment" button.

The Wall Street Journal ran a story this morning detailing drug companies' push for the proposal. The reporter did not seek a response from any consumer or patient group.

Posted by gooznews at April 18, 2008 08:15 AM