FDA’s Latest Off-Label Guidance: Five Practical Takeaways

On Tuesday, October 24, FDA announced the availability of a revised draft guidance document entitled “Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers.” The document is a revised version of a 2014 draft guidance document addressing the dissemination of published materials related to off-label use (including reprints of published journal articles), which was itself an attempt to revise the 2009 final guidance document addressing off-label reprints.

The revised draft reflects significant changes from the prior documents. For example, the document:

• Adopts new terminology for the communications within its scope, which are now described as communications of “scientific information on unapproved use(s)” (SIUU)
• Expands the scope of the guidance to include two new communication types: materials from independent clinical practice resources and firm-generated presentations of scientific information from an accompanying published reprint
• Introduces significant new standards and recommendations with respect to all the following:
  • Determining when a study or analysis is appropriate for communication under the guidance, in that it should be “scientifically sound” and “clinically relevant”
  • Substantive disclosures to be included 
  • Several new “presentational considerations,” including a recommendation to avoid “persuasive marketing techniques”

These changes and others raise many questions. Below are five key takeaways from a practical perspective. In general, while the document provides useful discussion of two new types of communications that FDA recognizes as appropriate, the remainder presents challenges. In addition, FDA has provided only a short window to submit comments, which are due on December 26, unless extended by further FDA action.

Practical Takeaways

1. New types of communications are recognized as appropriate.

Under the revised draft, FDA for the first time expressly permits the use of two new communication types: materials from independent clinical practice resources  and firm-generated presentations of scientific information from an accompanying published reprint.  The document also helpfully acknowledges the potential for SIUU to be communicated through diverse media and communication modalities (e.g., digital channels and commercial exhibit halls). At the same time, the document provides guardrails for firms to ensure that SIUU communications are separate from promotional communications, including by presenting SIUU on separate webpages that are not directly linked from promotional communications or in a separate space from promotional communications in exhibit booths.

2. The revised draft appears narrowly focused on communications intended to guide clinical decision-making.

The revised draft applies to communications with healthcare providers (HCPs) “engaged in making clinical practice decisions for the care of an individual patient.” The document and accompanying Federal Register notice also state that FDA intends to develop a separate policy for communications with “researchers.” The intended meaning of these limitations — as well as the document’s focus on “clinical relevance” and avoidance of “persuasive marketing techniques” — is unclear, but they generally read as if the only possible rationale for dissemination of SIUU would be to influence clinical decision-making in a manner that is similar to a promotional communication. In this way, the document appears to be significantly narrower in scope than what was covered by the prior documents and than the full range of legitimate, nonpromotional purposes for which companies may want to communicate SIUU. As a result, companies planning to proceed under the revised draft should carefully vet whether all the communications they have historically engaged in are still within scope.

3. The revised draft does not expressly answer significant questions about who may be involved, or how, in SIUU communications.

The revised draft does not include any explicit references to the roles of company personnel involved in SIUU communications. This contrasts with the prior documents, which included recommendations for scenarios where a sales representative delivers a reprint to a physician, including the recommendation that any questions be referred to a medical/scientific officer or department independent of the sales and/or marketing departments. It is unclear whether this change was intended to signal that there should no longer be sales/marketing involvement at all or whether FDA is indifferent so long as the SIUU is delivered separately from “promotion.” As a result, companies proceeding under the revised draft will need to make decisions about this without the benefit of explicit recommendations from FDA.

4. Applying the new disclosure recommendations may be especially challenging.

The revised draft sets forth recommendations for many substantive disclosures to be included in SIUU communications, including disclosures of relevant information from the FDA-approved labeling, such as approved uses, contraindications, or limitations of use. This also includes recommendations to disclose “all material aspects of study design, methodology, and results” and related limitations. Moreover, any firm-generated presentations of scientific information from an accompanying reprint should “provide all information necessary for HCPs to interpret the strengths and weaknesses and validity and utility of the presented information.” Cumulatively, these recommendations are quite onerous and may provide FDA and others with broad discretion to second-guess firm decisions about disclosures and other efforts to ensure that SIUU communications are truthful and nonmisleading. This also potentially opens the door to enforcement actions and litigation similarly premised on after-the-fact views taken by the Department of Justice, whistleblowers, or others.

5. Manufacturers face potential liability for “off-label” promotion based on communications that fully comply with the revised draft.

The revised draft includes, for the first time, a veiled warning that even full compliance with its recommendations could result in liability for “off-label” promotion. It states that “if a firm shares an SIUU communication with HCPs in a manner that is consistent with the recommendations in this guidance, FDA does not intend to use such communication standing alone as evidence of a new intended use” (emphasis added). In other words, the document asserts that a communication consistent with the guidance could, with other evidence, be used as evidence of a new intended use. The potential liability is further underscored by related language in the document, which repeats FDA’s position that “intended use” may be established by evidence from “any relevant source,” including evidence other than labeling, promotional claims, or advertising. Accordingly, companies should evaluate risk of SIUU communications in the broader context of their activities relating to a particular off-label use and employ comprehensive compliance practices informed by analysis of available data to control that risk.