A new draft guidance document released by the US Food and Drug Administration (FDA) aims to clarify the ways in which a pharmaceutical or medical device manufacturer may use scientific and medical literature to promote its products, even if the literature doesn't conform to the product's FDA-approved uses.
Such practices straddle a fine line between marketing and commercially protected free speech. FDA has long regulated the dissemination of company-sponsored or -generated studies that include information that has not been specifically cleared or approved by FDA, or does not meet rigorous standards.
But where regulation becomes tricky is when the research is independent and pursued for scientific, rather than promotional, reasons. For example, how would a company make healthcare providers aware of information pertaining to new clinical practice guidelines that involve a new but unapproved use of their device? What about distributing medical texts that mention off-label uses of a drug?
FDA's new draft guidance document, Distributing Scientific and Medical Publications on Unapproved New Uses - Recommended Practices, is meant to provide life science companies with a checklist for making sure they stay within the acceptable limits of promotion of scientific and medical publications.
The guidance is a revision of a 2009 draft guidance, Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved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. That guidance came under fire from life science companies, which argued that it restricted their ability to "promote the public health" by distributing scientific information informing the safe and effective use of their products.
Labeling, the manufacturers said, cannot be all-encompassing, and products and healthcare providers must rely on outside sources of information. This was seen as be especially pertinent since healthcare providers may use products off-label, even as companies cannot promote those same uses.
The companies specifically called for "clearer regulation" about acceptable off-label promotion. While FDA's newest draft guidance doesn't answer that call directly-the agency is still considering the request and working on a response-it does answer it in the context of scientific and medical literature.
FDA's guidance forms a checklist of sorts that companies will need to check against each instance of literature they wish to promote.
Scientific and medical journal articles, for example, should be from a peer-reviewed journal, be distributed in unabridged form (i.e. reprint), contain information from an "adequate and well-controlled clinical investigation" and be "scientifically sound."
In addition, the FDA-approved labeling should be disseminated along with the literature, as well as a comprehensive bibliography of information from other publications (including contradictory literature) and separate from any promotional literature.
In short, FDA calls for an emphasis on science-not promotion. As such, the guidance also calls for manufacturers to ensure that literature is not false or misleading, and does not contain information that could endanger a patient.
FDA also recommends that literature not be funded, either in whole or in part, by a company. Companies should also steer clear of highlighting or summarizing portions of the literature, having any influence over the writing or editing of the literature, or be "primarily distributed by a drug or device manufacturer."
"Rather, it should be generally available in bookstores or other independent distribution channels where periodicals are sold," FDA said.
Other recommendations include the inclusion of a "prominently displayed and permanently affixed" disclosure of the company's interest in the products discussed in the journal article, a statement that claims have not been approved or cleared by FDA, the financial interests of authors, the sources of funding for the study (if they are known to the manufacturer) and all significant risks or safety concerns known about the unapproved use or uses of the products.
Other Requirements: CPGs and Medical Reference Texts
Similar requirements are in place for medical reference texts, though FDA places a higher emphasis on the expertise of the editors and how current the information is (i.e. should be the latest version). Chapters from a medical reference text may also be distributed, in which case they must be unaltered/unabridged.
FDA's guidance also includes a section on the use of clinical practice guidelines (CPGs), which the agency says must be "trustworthy" under a six-part framework. CPGs should therefore:
- be based on a systematic review of the existing evidence
- be developed by experts and representatives from key affected groups
- consider important subgroups and patient preferences
- emanate from a transparent process
- provide a logical explanation of care options
- be part of an ongoing revision process based on evidence
Manufacturers wishing to disseminate CPGs should make sure they are current, delivered separate from promotional materials, state the manufacturer and its interests and be unaltered/unabridged.
FDA said it estimates that each distribution will take approximately four hours to complete, with an estimated 40,000 disclosures per year.
In an accompanying Federal Register notice, FDA also said it continues to consider ways to:
- facilitate the exchange of scientific information
- allow manufacturers to respond to unsolicited requests for information about unapproved or uncleared uses
- allow industry interactions with formulary committees, payors and "similar entities"
"FDA is considering a range of options for responding to questions about industry participation in scientific discussions and for addressing industry dissemination of new scientific information related to approved or cleared uses of marketed drugs and devices," it said.
Federal Register Notice