Left to Interpretation: Navigating FDA’s Revised Guidance on SIUU Communications

Archana Sah
AS Pharma Advisors
Elizabeth Johnson
Montana State University
Mark & Robyn Jones College of Nursing
Isaac R. Rodriguez-Chavez
4Biosolutions Consulting

n October 2023, the FDA released a revised draft guidance, reshaping the communication landscape between firms and healthcare providers (HCPs) regarding scientific information on unapproved uses (SIUU) of medical products. This guidance supersedes the 2014 version, spotlighting the impact of off-label or separately indicated medical products on clinical decision-making. The update marks a shift by acknowledging the potential use of real-world evidence (RWE) and data (RWD) in providing scientifically sound information on unapproved products. Incorporating electronic health record (EHR) data opens avenues for broader clinical insights, but challenges like data quality variability and reporting bias require careful consideration.

There is a strong need for improved interpretation strategies and transparent communication between HCPs and firms. This article addresses the knowledge gaps and interpretation challenges highlighted by the updated guidance and offers recommendations to enhance comprehension, promote integrity, and support responsible prescribing practices in the realm of off-label usage of medical products.

Revised Guidance: Improving Scientific Information on Unapproved Uses Communications

The generalized term for the communication of scientific information pertaining to unapproved uses of a medical product is known as Scientific Information on Unapproved Uses (SIUU) communication. Types of communication and media formats highlighted in the revised draft guidance include reprints of published scientific journal articles and clinical reference resources, such as clinical practice guidelines or reference material, as well as presentations created based on reprints (conference materials).

The FDA emphasizes the crucial role of these SIUU communications in supporting clinical decision-making, stressing the necessity for truthfulness, scientific accuracy, and provider-friendly crafting. Four key evaluation criteria—strengths, weaknesses, general validity, and clinical utility—are set to determine the interpretability of SIUU communications.

Burden on Healthcare Providers

HCPs now face the responsibility of evaluating SIUU communications, a challenge exacerbated in non-research-centric settings. Addressing biases in interpreting strengths and weaknesses is essential, yet tools or decision frameworks catering to diverse provider backgrounds are lacking. Validity assessment demands robust literature interpretation skills, blending industry-provided SIUU communications with evidence-based sources.

Bridging Interpretation Gaps

SIUU communications might favor high-resource perspectives, hindering comprehension in low-resource settings (e.g., critical access hospitals, skilled nursing facilities, free-standing clinics). Effective communication between diverse healthcare providers, patients, and firms is vital and emphasizes the necessity for the DEPICT ACT that aims to enhance diversity in clinical trials and improve representation in diverse communities. Better representation of patient populations congruent to the disease process or target of interest further supports pragmatic post-marketing utilization, which starts at socializing healthcare providers to the applicability of clinical trial results to their practice in these diverse communities.

Demographic Variances in Off-Label Usage

Certain demographics, like pediatric patients, encounter higher rates of off-label drug usage, often due to knowledge deficits among healthcare providers pertaining to label interpretation, side effect profiles, adverse reactions, and information repositories which itemize post-marketing drug reactions. Firms need to ensure timely and accurate information dissemination to address these gaps and ensure patient safety.

Integrity Concerns and Recommendations

Off-label marketing risks compromise medical literature integrity and implicate researchers in potential unethical activities. To counter perceptions of biased communications, enhanced transparency and rigor in presenting investigational product profiles are crucial. Leveraging RWE and RWD-driven research could mitigate biases and enhance awareness about off-label product usage across healthcare provider roles. Firms may further support transparency and rigor through collaborative, industry-wide development of materials that help healthcare providers interpret SIUU communications and foster awareness of reputable resources to guide clinical decision-making. Examples include expansion of “Dear Provider” letters, cover sheets, or facility-based training modules that are easy to deploy across both low- and high-resource healthcare systems. More so, these materials may support initiatives via the DEPICT ACT by utilizing the cultural or normative lexicon of those communities that firms are prioritizing for recruitment and retention in clinical trials. Together, these recommendations assist in the development of trust and rapport with communities, healthcare providers, and patients which will propagate responsible prescribing practices of off-label use of medical products and stewardship of regions of interest for representative data in clinical trials.

Embracing Transparency and Rigor

The updated FDA guidance offers a gateway to rectify biases in medical communications. Firms can aid comprehension by creating interpretation guides that use healthcare-friendly language and demystify critical sections of SIUU communications. Additionally, tracking off-label prescriptions could prompt independent evaluations for safety, efficacy, and tolerability, empowering HCPs with the evidence needed to make informed decisions.

To adapt to these changes, fostering transparent communication and upholding scientific rigor are pivotal. Aligning with the revised FDA guidance not only augments communication but also reinforces the credibility of medical information available to healthcare providers, ultimately advancing patient care and safety.