Washington Editor

The FDA is considering permitting drug and device makers to more broadly use published scientific and medical journal articles about unapproved, or off-label, uses when promoting their FDA-approved products to physicians.

While physicians are free to prescribe drugs and devices for off-label uses, manufacturers are banned from promoting their products for indications not approved by the FDA. However, the agency in a new draft guidance document issued Friday, proposed that firms under certain circumstances may distribute journal articles and other publications about the off-label uses of approved products.

The new guidelines would give drug and device makers a broader use of journal articles in marketing efforts than has been allowed in past years.

"Articles that discuss unapproved uses of FDA-approved drugs and devices can contribute to the practice of medicine and may even constitute a medically recognized standard of care," Randall Lutter, FDA deputy commissioner for policy, said in a statement.

The public has 60 days to comment on the new guidelines, which are being opposed by some consumer advocates and members of Congress.

Rep. Henry Waxman (D-Calif.), who obtained a copy of the draft guidance document in November, called the FDA's plan to allow the use of journal articles to promote off-label uses "ill-advised." (See BioWorld Today, Dec. 3, 2007.)

The draft guidelines, he said in a Nov. 30 letter to FDA Commissioner Andrew von Eschenbach, carves a "large loophole in the law" that ultimately lets firms short-circuit the drug approval process.

"Published reports of company-funded studies can be biased in favor of the company's product," asserted Waxman, who is chairman of the House Committee on Oversight and Government Reform.

"Allowing drug and device companies to freely disseminate these articles can result in doctors using questionable study results to guide their prescribing habits," he said.

In addition, Waxman argued, permitting marketing through journal articles "can reduce the incentive for drug and device companies to conduct the rigorous studies needed to win full FDA review and approval, leaving physicians and patients without definitive data on the benefits and risks of medical products."

He noted that the Food and Drug Administration Modernization Act (FDAMA) of 1997 included a temporary provision, known as Sec. 401, which allowed manufacturers to disseminate journal article reprints if, among other things, a firm submitted the articles to the FDA for review 60 days before dissemination and the company had submitted an application seeking approval of the new use to FDA.

Those conditions, Waxman noted, addressed the policy concerns underlying the prohibition against marketing of unapproved uses.

However, Congress included a sunset date of Sept. 30, 2006 for the provision, and lawmakers made no attempt to renew Sec. 401 in the latest FDA reform package, known at the Food and Drug Administration Amendments Act of 2007, which was enacted Sept. 27.

The FDA's newly proposed plan, Waxman charged, "would permit far more dissemination of articles on unapproved uses than was sanctioned under FDAMA."

The guidelines, he contended, "appear to be an effort by FDA to displace Congress and establish by administrative fiat a new system for use of journal articles that lacks the safeguards set by Congress."

Sidney Wolfe, director of health research at the Ralph Nader-founded consumer advocacy group Public Citizen, said the FDA's proposal "contrasts the current recklessness of the agency with the more consumer-protective FDA of 10 years ago."

If finalized, he argued, the draft guidance "constitutes a health threat because it encourages drug companies, who have no reason to fear FDA sanctions, to promote drugs for purposes not proven to be safe and effective."

Wolfe echoed a call made last week by Rep. Bart Stupak (D-Mich.), chairman of the House Energy and Commerce Subcommittee on Oversight and Investigations, for FDA Commissioner Andrew von Eschenbach to step down. (See BioWorld Today, Feb. 19, 2008.)

"Almost every week brings new evidence of the FDA's dangerous attitude about the public's health and demands a change in leadership at the agency, starting with the commissioner," Wolfe charged.

Waxman noted that the FDA has uncovered instances when firms have distorted study results to make their products appear better than they are.

For instance, he said, an FDA review of studies about selective-serotonin re-uptake inhibitors (SSRIs) found that at least two industry-funded studies failed to meet their primary efficacy endpoints, yet the published articles stated that the drugs were effective, Waxman noted.

Manufacturers of SSRIs, he asserted, also suppressed studies that failed to show effectiveness in children.

In addition, Waxman said, a whistleblower lawsuit filed under the federal False Claims Act revealed that Parke-Davis, which later was acquired by Pfizer Inc., engaged in what the firm called a "publication strategy" to promote unapproved uses of the epilepsy drug Neurontin (gabapentin).

Parke-Davis, Waxman explained, hired marketing consultants to create studies and find willing physicians to "author" them. However, only studies with positive results were selectively published.

Pfizer ultimately paid $430 million to settle civil and criminal liability claims related to the off-label promotion of Neurontin.

Since the FDA's proposed guidance gives the responsibility to manufacturers and their "tens of thousands" of marketing representatives of putting a journal article in the correct context and ensuring that physicians receive balanced information, the FDA's enforcement of the draft guidance will be "particularly difficult," Waxman maintained.

But the agency contended that, although the FDA's guidance documents are not rules, but merely suggestions, and Sec. 401 is now expired, regulators have retained the legal authority under the Federal Food, Drug and Cosmetic Act to determine whether distribution of an article or publication constitutes promotion of an unapproved new use of a product and if those activities cause a product to be considered misbranded or adulterated.

The FDA's draft guidance document calls for articles to be published by organizations that have editorial boards and that the articles are peer-reviewed. In addition, the guidelines recommend that organizations fully disclose any conflicts of interest or biases for all authors, contributors or editors associated with the journal article.

The guidelines also recommend against distribution of special supplements or publications that have been funded by one or more of the manufacturers of the product in the article.

Articles that are not supported by credible medical evidence are considered false and misleading, the FDA warned, and should not be distributed.