March 3, 2014 – The FDA announced today the availability of a new draft guidance (2014-04560) on distributing scientific and medical publications on unapproved uses that updates a 2009 draft guidance on the topic, provides recommended practices for the dissemination of scientific or medical journal articles and scientific or medical reference texts and, importantly, adds clinical practice guidelines (CPGs) to the mix.

The Federal Register notice regarding the revised guidance also states that the FDA continues to consider specific requests made in July 2011 and September 2013 citizen petitions, filed on the behalf of multiple prescription drug and medical device manufacturers, related to the agency’s approach to the distribution of scientific and medical information reflecting unapproved or uncleared uses.

“This draft guidance shows that the agency is getting the message that it must conform its policies and practices to the First Amendment,” said Coalition for Healthcare Communication Executive Director John Kamp. “Manufacturers should be able to distribute truthful information – in the form of journal articles, medical textbooks and practice guidelines.”

The agency is requesting comments on this draft guidance and states in the Federal Register notice that it also is soliciting input on the following three issues:

• Further explanation of “scientific exchange”
• Development guidance on the issue of manufacturer responses to unsolicited requests for information relating to unapproved or uncleared uses
• Consideration of draft guidance on industry interactions with formulary committees, payers and similar entities

Further, the 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.”

In the revised draft guidance, the FDA reiterates its position that there are inherent risks in promoting drugs and medical devices that lack FDA approval or clearance and in promoting new intended uses for previously approved or cleared products. “The public health often is not well served when [physician] judgments rest on anecdotal experience or even preliminary scientific study,” the agency states. “Too often, the promise of safety and effectiveness made by such sources has not been demonstrated when adequate and well-controlled clinical studies are completed.”

However, the agency also states that its 2009 draft guidance on good reprint practices “recognized that the public health may benefit when health care professionals receive truthful and non-misleading scientific or medical publications on unapproved new uses,” and that this 2014 revised draft guidance recognizes that value as well.

Unlike the 2009 draft guidance, the 2014 draft guidance separates out scientific or medical journal articles, scientific or medical reference texts, and includes CPGs. Each is summarized below.   

Scientific or Medical Journal Articles

The FDA states in the revised draft guidance that companies wishing to distribute journal articles that include information on unapproved/uncleared uses of their products should follow the following recommendations that the journal articles:

• Be published by an organization which has an editorial board that uses independent experts with specific expertise in the article’s subject and adheres to a policy of full disclosure of conflict of interest
• Be peer-reviewed and published in accordance with the peer-review procedures of the organization
• Be in the form of an unabridged reprint or copy of the article
• Contain information that describes and addresses adequate and well-controlled clinical investigations that are considered scientifically sound by experts with appropriate training;
• Be disseminated with the approved labeling
• Be disseminated with a comprehensive bibliography
• Be disseminated with a representative publication, when such information exists, that reaches contrary or different conclusions regarding the unapproved use, “especially when the conclusions of the articles to be disseminated have been called into question by another publication”
• Be distributed separately from the delivery or information that is promotional in nature (e.g., a reprint should not be attached to any promotional material a sales representative delivers to a physician office).

The revised draft guidance also states that these materials must not be false or misleading, contain information recommending or suggesting a use that makes the product dangerous to health, and lists six specific activities that manufacturers should not do when distributing these materials.

The agency also specifies that these materials should be accompanied by a prominently displayed and permanently affixed statement disclosing the manufacturer’s drug included in the journal reprint, clarifying that some or all uses described in the reprint have not been approved by the FDA, listing any journal article author known to the manufacturer as having a financial interest in its company, identifying any person known to the manufacturer who has provided funding for the study, and enumerating all significant risks or safety concerns associated with the unapproved use(s) discussed in the journal article.

Types of journal reprints specifically excluded from those recommended by the FDA include letters to the editor, abstracts, reports of healthy volunteer studies, and publications consisting or statements or conclusions without substantive discussion of the relevant investigation or data on which they are based.

Scientific or Medical Texts

According to the revised draft guidance, scientific or medical reference texts should:

• Be based on a systematic review of the existing evidence
• Be published by an independent publisher
• Be the most current version
• Be authored, edited and/or contributed to by experts who have demonstrated expertise in the subject area
• Be peer-reviewed by experts with relevant medical or scientific expertise and published in accordance with peer-review procedures of the publisher
• Be sold through usual and customary independent distribution channels
• Be distributed separately from the delivery of information that is promotional in nature
• Contain a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing that some or all uses described in the text might not be approved by the FDA. Financial interests of authors in the company should be disclosed and the statement should be places by a sticker, stamp or other means on the front cover of the textbook.
• Be disseminated with the approved product labeling if a text is distributed in its entirety but individual chapters devote primary substantive discussion to an individual product or products of the manufacturer distributing it.

The revised draft guidance also includes guidelines for when a manufacturer distributes an individual chapter of a textbook in lieu of the complete text, includes the same restrictions as listed for journal reprints and lists the same six activities that are not advisable.

Clinical Practice Guidelines

The FDA includes new guidelines in the revised draft guidance document for CPGs. Specifically, it states that manufacturers wishing to disseminate CPGs – statements that include recommendations intended to help clinicians make decisions for individual patient care – should only do so when the CPGs are “trustworthy,” a status that is defined in Institute of Medicine standards.

According to the revised draft guidance, manufacturers wishing to distribute a “trustworthy” CPG in its entirety should:

• Ensure that the most current version of the CPG is disseminated
• Distribute the CPG separately from the delivery of information that is promotional in nature
• Ensure that the CPG Contain a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing that some or all uses described in the CPG might not be approved by the FDA. Financial interests of authors in the company should be disclosed and the statement should be places by a sticker, stamp or other means on the front page of the CPG.

There are specific instructions in the guidance for distributing individual sections of a CPG, and the restrictions and activities that are not advisable under the guidance are repeated in this section as well.

Comments on the revised draft guidance are due by May 2.