Off the Label: Contrary to Reports, FDA Guidelines for Off-Label Promotion Tighten Loopholes
It was interesting to read recent media reports in such prominent outlets as Bloomberg.com and the Wall Street Journal about the FDA’s plans to set guidelines for the kinds of literature drug makers can use to support the off-label use of FDA-approved drugs. Originally, the FDA stipulated that drug manufacturers could disseminate information on unapproved, off-label uses of FDA-approved products, under Section 401 of the Food and Drug Administration Modernization Act that expired on Sept. 30, 2006. It took a while but on Feb. 15, 2008, the agency announced new guidelines under the title “Good Reprint Practices.”
The whole idea is that while the FDA recognizes that off-label use is common, and indeed quite legal, drug companies need strict guidance on what they disseminate regarding those uses. Contrary to what some of those news reports suggest, the FDA is not opening the door for drug companies to promote off-label uses of drugs. Instead, it puts very precise rules and standards in place for what the companies can use as supporting evidence, such as peer-reviewed publications.
In general, the FDA approves drugs only for certain indications, and this information is contained in the FDA label for the product. However, there is nothing illegal about healthcare professionals prescribing FDA-approved drugs for non-indicated uses, such as administering an anti-epileptic drug to treat bipolar disorder, for instance. Indeed, it is estimated that around 20 percent of all drugs are prescribed for off-label uses, particularly in the psychiatric arena. However, it is illegal for manufacturers to actively promote drugs for non-indicated uses.
Limiting What Companies Can Distribute
The new guidance (http://www.fda.gov/oc/op/goodreprint.html) recommends that individuals (such as drug company representatives) who disseminate literature in support of off-label use, use only letters to the editor, publication abstracts, and reports of Phase 1 trials in healthy subjects from peer-reviewed journals with recognized editorial boards. It also allows for reference publications that contain little or no substantive discussion of the relevant investigation or data. The publications should be generally available in bookstores or other independent distribution channels where medical textbooks are sold, according to the guidelines.
The guidelines also suggest that the articles should not be edited, abridged, marked, or highlighted in any way, and that reprints or copies should be accompanied by the FDA-approved labeling and an extensive and comprehensive bibliography. The articles should not be physically attached to any promotional material by sales representatives, nor should they constitute a subject of discussion during sales presentations. Similarly, sales representatives should not distribute these reprints at conferences.
Lastly, the FDA recommends that a journal reprint or copy also should carry a prominently displayed statement disclosing the following:
- The uses described in the information have not been approved or cleared by FDA, as applicable to the described drug or medical device.
- The manufacturer’s interest in the drug or medical device that is the subject of the journal reprint or reference text.
- Any author’s financial interest in the product or manufacturer.
- The funding source for the study, and
- Any significant risks or safety concerns the manufacturer knows about concerning the unapproved use that are not discussed in the journal article or reference text.
It Remains Illegal to Promote Off-Label Use
Finally, it should be recognized that it is illegal for a drug company to promote off-label use for a drug or device that constitutes a “new use” for that drug or device. If such promotion is carried out, then the FDA retains legal authority to decide upon the condition of unapproved “new use” and whether the distribution of an article or publication constitutes promotion of a new use. In some cases these decisions can result in a product being deemed misbranded or adulterated under the federal Food, Drug and Cosmetic Act.
Given that healthcare professionals can legally prescribe drugs for off-label use, the FDA guidelines represent a significant advance in this whole area. I find it puzzling to read comments in the press and in online blogs about how this is going to open up the area of unapproved, off-label use and thereby put the public’s safety as risk because the FDA is now going to completely endorse publications promoting such use. If anything, this proposal sets very strict and sensible boundaries for promoting off-label use. As Randall Lutter, an FDA deputy commissioner, said in a news release referring to the publications for off-label use, they "can contribute to the practice of medicine and may even constitute a medically recognized standard of care.”
Media Fuss Side Effect
One side effect of the media fuss was that Democratic Rep. Henry Waxman of California wrote to the FDA suggesting that it rethink the guidance. He said he was worried that it would create a large loophole in the laws against off-label promotion. Actually, it tightens loopholes.
In the end, it is the doctors and healthcare practitioners who must decide on how to use a drug for a given condition. If an FDA–approved anti-epileptic drug has been shown to significantly improve a bipolar disorder in independent and peer-reviewed studies, then doctors and healthcare practitioners are the ones who are going to be in the best, and only, position to determine how best to treat the patient, on a case-by-case basis. With these guidelines in place, the promotion or advocacy of off-label use by drug—or medical device—companies is likely to be severely restricted.
- Download DOWNLOAD PDF