Commenters split on FDA’s off-label communication guidance

Drug and device makers are asking the US Food and Drug Administration (FDA) for more flexibility in communicating scientific information on off-label uses of drugs, biologics and devices, while at least one nonprofit group supported strict standards for communications on unapproved uses.

In the draft guidance, issued in October 2023, FDA outlined considerations for sponsors/manufacturers to share scientific information on unapproved uses (SIUU) of approved/cleared medical products, also known as off-label use, with healthcare providers. The draft guidance discusses firms sharing published scientific or medical journal articles (reprints), published clinical reference resources, such as clinical practice guidelines (CPGs), and firm-generated presentations of scientific information from an accompanying published reprint.

The latest draft supersedes the 2014 version of the guidance. (RELATED: FDA expands scope of off-label guidance to include presentations from reprints, Regulatory Focus 24 October 2023)

Early phase evidence

Drugmaker AbbVie commented that the draft SIUU guidance does not go far enough to support clinical decision making by healthcare providers. AbbVie specifically objected to FDA’s suggestion that communications related to early phase clinical trials are not clinically relevant. “We believe that such exclusions, if finalized, would be arbitrary and needlessly limit the communication of scientific information relevant to clinical practice decisions and the best interests of individual patient care and treatment,” AbbVie wrote.

AbbVie noted that in oncology and rare diseases, it is not uncommon for medical products to be approved based on data from Phase 2, and even Phase 1 trials. In those cases, the studies met FDA’s “substantial evidence” standard. “It is important for firms to responsibly share off-label information from a Phase 2 study with [a healthcare provider], even when that study does not qualify as ‘substantial evidence.’ In cases where a publication contains off-label information from a Phase 2 study that does qualify as ‘substantial evidence,’ an FDA approval is likely imminent,” AbbVie commented.

GE HealthCare (GEHC), a medical technology company, asked FDA for clarification on the types of scientific evidence FDA considers preliminary and not clinically relevant. For example, GEHC asked if pediatric efficacy and safety results from a Phase 3 clinical study of a drug approved only in adults would be considered preliminary evidence if the data was otherwise scientifically sound.

GEHC asked the agency to provide examples of preliminary data to correspond with examples offer in the draft guidance on what the agency considers appropriate studies.

However, the nonprofit think tank National Center for Health Research supported FDA’s position that case reports and early-stage studies are not appropriate communications, even when limitations are disclosed. “Data gathered from these types of studies are insufficient to permit a thorough clinical evaluation for unintended use of a medical product. Moreover, since not all physicians have expertise in study design and data interpretation, providing such information could easily be misleading or misunderstood,” the National Center for Health Research commented.

Scope of SIUU

AbbVie also took issue with the narrow scope of allowable SIUU communications that could be made in the form of firm-generated presentations. The draft guidance specifies firm-generated presentations of scientific information from an accompanying published reprint as SIUU communications, but does not include presentations that feature reference texts or CPGs, for example, even though those publications can be shared directly.

“So long as the source materials are reviewed with similar rigor, we [see] no reason for FDA to limit the scope of firm-generated SIUU Communications to truthful, non-misleading, ‘scientifically sound’ and ‘clinically relevant’ summaries of reprints, and to not include similar summaries of CPGs, reference texts and independent clinical practice resources,” AbbVie commented.

In contrast, the National Center for Health Research supported the limitations on the use of firm-generated presentations, noting that it is difficult to present the full context needed for data interpretation in PowerPoint and oral presentations. Additionally, presentations have the potential to “unintentionally misrepresent or manipulate results” through the use of figures and graphs that don’t provide full context on the information.

Comments on revised draft guidance

Commenters split on FDA’s off-label communication guidance

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