FDA finalizes guidance on off-label communications

The US Food and Drug Administration (FDA) finalized guidance to industry on allowable communications to health care providers about off-label drug and device uses.

The Q&A document, issued on 6 January 2025, outlines the agency’s enforcement policy for firm-initiated communications to health care providers that contain scientific information on unapproved uses (SIUU) for approved or cleared drug and device products.

“FDA is issuing this guidance to provide reassurance to firms that, if they choose to provide communications consistent with the recommendations of this guidance, FDA does not intend to use the firm’s dissemination of such communication standing alone as evidence of a new intended use. Additionally, FDA does not expect a firm to submit such a communication to the Agency at the time the communication is initially shared with HCPs,” the agency wrote.

The final guidance applies to firm-initiated communications of SIUU based on published scientific or medical journal articles (reprints) and published clinical reference resources, such as clinical practice guidelines, reference texts and digital clinical practice resources. It also applies to firm-generated presentations that include these sources. The guidance is aimed at balancing the need for premarket review with clinician interest in scientific information about off-label uses.

The agency originally addressed this issue through final guidance in January 2009 but updated that guidance through a draft document issued in March 2014. FDA again updated the guidance in October 2023. Comments on the most recent draft guidance were split, with some drugmakers emphasizing the importance of communicating early clinical trial data to health care providers and some groups supported limits on industry-generated presentations. (RELATED: Commenters split on FDA’s off-label communication guidance, Regulatory Focus 11 January 2024)

Choosing sources

Choosing appropriate source publications for SIUU communications is critical. Studies and analyses should be “scientifically sound,” according to the final guidance document. For drugs, that typically means a randomized, double-blind, concurrently controlled superiority trial but other well-designed trials are acceptable, such as an “early-phase” randomized, double-blind trial that has a prespecified statistical analysis plan comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity for two drug products. Other acceptable studies include meta-analyses, cohort or case-control studies, open-label studies, single-arm studies, externally controlled trials and observational studies.

On the device side, studies are most likely to be considered scientifically sound if they are well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories from experts, and reports of “significant human experience” with a marketed device.

Firms should consider the existing scientific knowledge before disseminating studies to ensure they are not sharing information that has been refuted, corrected, or retracted.

“Additionally, in a case where understanding of a disease has advanced and shown that certain outcome measures used in studies do not reflect an effect on the disease, sharing source publications that are based on studies that used those outcome measures would not be consistent with the recommendation that firms take into account existing scientific knowledge when determining whether a source publication should be included in an SIUU communication,” FDA wrote in the final guidance.

Clinical practice guidelines should generally have rating that indicate the strength and quality of evidence supporting the recommendations and be updated new evidence is available.

Firm-generated materials

The final guidance includes additional recommendations on firm-generated presentations since they do not have the “same level of independence in their development” as source publications. The guidance calls on firm-generated presentations of SIUU from one or more source publications to include the source publications with the presentation, explain the study limitations, and disclose that it is a firm-generated presentation.

Firm-generated presentations should not imply that a study “represents larger or more-generated experience with the medical product than it actually does” or make representations about the safety or effectiveness of the unapproved use that are inconsistent with the source publication. Additionally, even if the conclusions about the unapproved use accurately reflect what is in the source publication, they must be attributed to the source publication and include disclosures of any authors, editors or contributors who received compensation from the firm.

FDA also recommends against the use of textual or graphic design elements that distort the scientific content by emphasizing only positive information or minimizing unfavorable data.

“In firm-generated presentations, a firm’s use of communication techniques to encourage the unapproved use of its medical product based on elements other than the communication’s scientific content does not appropriately serve the purpose of informing clinical practice decisions for the care and management of individual patients and therefore does not counterbalance the important government interests discussed in this guidance,” FDA wrote.

Final guidance

FDA finalizes guidance on off-label communications

Related topics

Recommended content

Welcome to the new RAPS Digital Experience