It was a big day in January 2009 when FDA finally issued guidance for manufacturers governing the distribution of medical journal articles and reference publications. While some guidance was better than no guidance, FDA received several comments asking for clarification on how the principles applied to medical textbooks, and also received two citizen petitions asking for information on how FDA might view the distribution of information in clinical practice guidelines ("CPGs"), which are recommendations for clinicians to use when making decisions for individual patient care. As a result, last Friday, FDA issued a new Draft Guidance revising the 2009 document to expand FDA’s guidance on good reprint practices to apply to medical reference texts and CPGs.
In the preamble to the new revised draft guidance, FDA makes clear that it continues to solicit comment concerning various aspects related to the guidance, such as information relating to “scientific exchange,” responses to unsolicited requests for information relating to unapproved or uncleared uses, and distribution of health care economic information to payors. The new guidance document, when finalized, will repeal and replace the 2009 Reprint Guidance.
Substantively, the Draft Guidance includes all of the principles and recommendations contained within the existing 2009 Reprint Guidance. FDA emphasizes that all distributed materials should not:
- Be false or otherwise misleading;
- Recommend or suggest use of the product in such a way that the product is dangerous to health when used in the manner suggested; nor
- Be marked, highlighted, summarized, or characterized by the manufacturer, in writing or orally, to emphasize or promote an unapproved use.
But because reference texts and CPGs are generally much longer and cover a wider range of topics than a journal article, the issues are more nuanced than a simple journal article. Accordingly, the new Draft Guidance adds two sections that detail specific recommendations governing these types of documents.
Readers can reference the document for details, so we will not reiterate them all here. The key elements for distributing a reference text containing information about an unapproved or uncleared use are that the text:
- Be based on a systematic review of the existing evidence;
- Be independently published;
- Be the most current version;
- Be written by experts in the subject area;
- Be peer-reviewed by other subject area experts;
- Be widely available through normal independent distribution channels;
- Not be distributed with any product promotional materials;
- Include a permanently affixed, and prominently displayed statement disclosing (1) the distributing manufacturer, (2) that some of the uses described in the text may be unapproved or not cleared by FDA; and (3) whether any specific authors have a financial interest in the manufacturer or its products; and
- If there are one or more chapters that primarily discuss unapproved or uncleared uses, be accompanied by the approved product label (or indications of use for a 510(k) cleared device).
If only part of a reference text is distributed, the guidance requires that:
- The overall reference text meets the requirements above;
- The permanently affixed, prominently displayed statement is placed on the distributed part of the reference;
- The affixed statement includes all known significant risks associated with the unapproved or uncleared use;
- The distributed part of the reference text be unaltered, unabridged, and extracted directly from the original referent text; and
- It be distributed with a copy of the approved product label (or indications of use for a 510(k) cleared device).
Clinical Practice Guides
Any CPG that includes information on unapproved or uncleared uses must meet Institute of Medicine (IOM) standards for whether it is a “trustworthy” guideline. According to IOM, a guideline is “trustworthy” if it:
- Is based on a systematic review of the existing evidence;
- Is developed by experts in the subject area;
- Considers important patient subgroups and patient preferences;
- Is transparently developed and funded such that biases are minimized;
- Provides logical relationships between treatment recommendations, health outcomes, and includes the quality and strength of the underlying evidence; and
- Is reconsidered and revised as new information becomes available.
Similar to reference texts, FDA lays out several requirements for CPGs that are distributed in their entirety, and additional requirements if only a section is used.
Although draft guidance is rarely an example of clarity, on the whole, the Draft Guidance provides helpful information regarding how manufacturers should think about reference texts and CPGs. For those who have been applying the 2009 Reprint Guidance to these texts, compliance with the Draft Guidance should be relatively straightforward.
The Draft Guidance is open for public comment for 60 days, until May 2, 2014.