Key Takeaways:
- FDA published a final version of its guidance document, "Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products" in January.
- The final guidance supersedes an October 2023 draft guidance. The 2023 draft guidance was based on a 2014 draft guidance "Distributing Scientific and Medical Publications on Unapproved New Uses — Recommended Practices" and represents 10 years of FDA's evolving thoughts on off-label communication with health care providers (HCPs).
- The updated final guidance maintains many elements of the policy outlined in the 2023 draft guidance, changes between the versions clear up ambiguities from the draft guidance and require firms to re-think certain aspects of their SIUU communications.
On January 6, 2025, FDA published a final version of its guidance document, "Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products." This guidance supersedes FDA's October 2023 draft guidance on the topic and describes FDA's enforcement policy regarding certain firm-initiated communications of scientific information on unapproved uses (SIUU) of a firm's approved or cleared medical products to health care providers (HCPs) engaged in prescribing or administering medical products to individual patients. Our previous alert on the 2023 draft guidance may be found here.
The final guidance document, while maintaining many of the core definitions and concepts of the draft version, includes some significant, notable changes. These changes clarify some ambiguous points from the draft version and exclude some aspects of the draft guidance policy that were confusing or difficult. We provide a high-level overview of some of the changes directly below.
Firm-Initiated Communication
The final guidance clarifies that FDA's SIUU policy applies to firm-initiated SIUU communications and not to unsolicited questions regarding unapproved uses. This point was implied in the draft guidance by reference of the applicability of Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices, but the final guidance document clarifies that the SIUU policy applies to firm-initiated, prospective presentation of unapproved uses.
Guidance Definitions
FDA clarified a few aspects of the SIUU policy through changes to definitions, notably the definition of SIUU Communication:
In the final guidance, "SIUU communication refers to a firm-initiated communication of scientific information on unapproved use(s) of the firm's approved/cleared medical product that:
- Is shared with HCPs engaged in prescribing or administering approved/cleared medical products to individual patients;
- Includes the disclosures recommended in this guidance; and
- Includes one or more of the following types of source
publications:
- Published reprints
- Published clinical reference resources, as follows:
- CPGs
- Reference texts
- Materials from digital clinical practice resources
An SIUU communication can also include a firm-generated presentation."
As discussed above, the updated SIUU Communication definition clarifies that SIUU communications are firm-initiated and may consist of firm-generated presentations. Furthermore, the audience and media of SIUU communications are now incorporated into the term's definition. Firm-generated presentations is defined earlier in the final guidance to consist of a firm's presentation of SIUU that uses one or more source publications that are then provided with the presentation.
Additionally, the term digital clinical practice resource has been added to the final guidance. It replaces the term "independent clinical practice resource" from the draft guidance document and the final guidance clarifies what constitutes a digital clinical practice resource by citing example sources in footnotes (e.g. Medscape and UptoDate).
Updated Questions and Answers
The updated Questions and Answers provide insight into FDA's evolving thoughts on SIUU communications between the draft and final guidance documents.
Q&A 1: What should firms consider when determining whether a source publication is appropriate to be included in an SIUU communication?
FDA now provides the following examples for what types of studies are considered "scientifically sound":
"For example, a scientifically sound study could include an early-phase randomized, double-blind, parallel assignment clinical study with a prespecified statistical analysis plan comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of two prescription drug products. Other examples of studies that could be consistent with this recommendation include meta-analyses, cohort or case-control studies, open-label studies, single-arm studies, externally controlled trials, and non-interventional (observational) studies."
These examples help clear up some of the ambiguity around what constitutes a "scientifically sound" study from the 2023 draft guidance, which generally characterized "scientifically sound" studies as those that "meet generally accepted design and other methodological standards for the particular type of study or analysis performed." The draft guidance mentioned that statistical robustness was a factor to be considered when assessing whether or not a study would be considered "scientifically sound," but the final guidance document's examples shed more light on what may constitute a "scientifically sound" study.
Additionally, FDA provided more context regarding the use of "outdated" studies in SIUU communications. FDA clarifies in the final guidance that a more recent study that generates a different outcome than a previous study does not necessarily make the previous study obsolete or inappropriate to disseminate. Rather, a firm should consider whether existing scientific knowledge has refuted a conclusion of an SIUU communication source publication or if an SIUU source publication was informed by a now-corrected long-held misunderstanding. The draft guidance required firms to determine whether source publications were still "clinically relevant," and the final guidance document instead includes factors that firms should consider when including or excluding source publications.
Q&A 2: What information should firms include as part of SIUU communications?
The second Q&A did not change much between the draft and final guidance. FDA did move the requirement that a firm mention a product REMS from a footnote to the main text, perhaps highlighting the importance of this disclosure.
Q&A 3: What presentational considerations should firms take into account for SIUU communications?
The third Q&A notably removed a paragraph that provided context regarding how SIUU communications should not use persuasive marketing techniques. The SIUU policy still prohibits presentation of material that is not "scientific content," but the draft guidance dedicated over a page to prohibiting "persuasive marketing techniques" in SIUU communications. This persuasive marketing technique discussion is notably absent from the final guidance document.
Additionally, while the draft guidance included a prohibition on combining SIUU communications with promotional, approved use communications, the final guidance adds and expands upon examples of this separation. The final guidance includes more detail for the previously provided examples related to conferences and product websites, and now includes examples related to email messages and in-person HCP visits. Notably, the final guidance mentions that, with appropriate separation, a firm representative may discuss approved uses and SIUU in the same HCP visit.
Lastly, the draft guidance recommended that firms consider using plain language in SIUU communications to facilitate comprehension. This requirement, which may have been difficult to achieve given the audience for SIUU, has been removed from the final guidance.
Q&A 4: What additional recommendations apply to reprints, CPGs, reference texts, and materials from digital clinical practice resources that are included in an SIUU communication?
The answer to question four has removed language regarding what constitutes a "scientifically sound" and "clinically relevant" reprint. The reprint section of the fourth Q&A still maintains the same scholarship requirements as the draft guidance, but the removal of the elaboration on these terms continues the trend of the final guidance document that less so focuses on providing SIUU communications for individual patients but rather to HCPs that treat individual patients.
The fourth Q&A now also contains a warning that Clinical Practice Guides (CPGs) that misrepresent or overstate findings from a study or analysis in light of the limitations of such study or analysis would not fall within the enforcement policy outlined in this guidance. Therefore, firms should scrutinize CPGs for inclusion in SIUU communications.
Q&A 5: What additional recommendations apply to firm-generated presentations of scientific information on unapproved use(s) provided with a source publication?
The fifth question was previously part of Q&A 4 in the draft guidance and covers additional recommendations to firm-generated SIUU presentations.
One of the major additions to fifth Q&A is the discussion surrounding "calls to value." The fifth Q&A clarifies that calls to value – a phrase that includes both a call to action and a value proposition – that pre-judge benefits of the product fall outside of the SIUU policy. FDA provides some examples of acceptable and unacceptable calls to value:
- Unacceptable: "Call FIRM X now for more information on [Medical product X] — it's the best option for your difficult-to-treat patients!"
- Acceptable: "Read now to learn more about this new data on Medical product X."
The fifth Q&A mentions that the main theme surrounding this call to value policy boils down to whether or not a communication is seen as an effort to convince an HCP to prescribe or use a product for an unapproved use or consists of a communication that provides an HCP with scientific information to evaluate and make a clinical decision.
Conclusion
While the core and intent of FDA's SIUU communications policy remains in place following publication of the final guidance, firms must account for the changes between the 2023 draft guidance and the January 2025 final guidance in their internal SIUU policies. Foley Hoag's FDA team is prepared to discuss the SIUU communication landscape and factors to consider for internal policies.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
