The United States Food and Drug Administration (FDA) received more than 130 comments on its draft guidance on clinical diversity, Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies. While the comments were largely positive, there were multiple calls for more information on the types of studies that require a Diversity Action Plan (DAP), applicability of DAP requirements to global trials, alignment on data collection categories for demographics, and what happens if a sponsor fails to meet the DAP requirements.
Comments on Definitions and Data Gaps
In its comments, the American Medical Association (AMA) requested that the FDA coordinate with the Office of Management and Budget’s Statistical Policy Directive No. 15, which incorporates many recommendations that the AMA previously submitted to the agency, including “the adoption of a single combined question on race and ethnicity.” AMA further recommended that the FDA “encourage the disaggregation of demographic data for historically minoritized and marginalized populations,” as stated in that same Policy Directive.
The Medical Device Manufacturers Association (MDMA) raised concerns about the lack of examples of how to address data collection issues and data gaps in the draft guidance. MDMA notes that in certain jurisdictions, certain demographic information is either not permissible to collect or it is restricted to certain populations that sponsors are able to enroll.
The Biotechnology Innovation Organization (BIO) submitted comments, opining that the agency should offer an example of an enrollment goal with disaggregation by required categories of race, ethnicity, sex, and age, “clarify[ing] the Agency’s DAP expectations, especially for enrollment goal categories that were previously not commonly utilized by sponsors.” BIO also referred to ambiguities in defining gender and sex, with the terms sometimes being used interchangeably, “it is important that these terms are used carefully throughout the guidance. It will be helpful for the final guidance to clarify whether the Agency will consider inclusion of gender (and other Sexual Orientation and Gender Identity data) to contribute to diversity enrollment goals.”
The Pharmaceutical Research and Manufacturers of America (PhRMA) echoed those comments, recommending that the FDA “define key terminology in the final guidance and initiate a process to achieve longer-term international harmonization on these terms.”
Comments on DAP Requirements
PhRMA emphasized the importance of definitions, saying, “PhRMA recommends that the final guidance acknowledge that a single DAP covering multiple studies evaluating a specific indication or condition may be appropriate or encouraged in some situations; if a single DAP is submitted, PhRMA recommends that the enrollment goals for each pivotal study may be presented individually.”
The Advanced Medical Technology Association (AdvaMed) also emphasized the importance of clarity on definitions, noting that there are instances where Investigational Device Exemptions (IDEs) may or may not require DAPs. AdvaMed therefore noted that the final version of the guidance should “provide sponsors the flexibility to design diversity action plans that are relevant to their specific device types and indications, with appropriate rationale.”
Accountability for Failure to Meet Requirements
The American Geriatrics Society raised concern over the fact that the DAP does not specify what is to happen if a sponsor fails to meet enrollment goals. To that end, they suggested ensuring accountability “through an enrollment analysis at the annual review of a sponsor’s trial and potential consequences of failing to meet ultimate enrollment targets.”
BIO noted that there will be sponsors that are “inevitably” unable to meet their enrollment targets “despite their good faith efforts.” They requested that the FDA acknowledge that “on occasion, the enrollment of study participants in complete alignment with the US prevalence or incidence of a given disease may be unrealistic; despite sponsor efforts, enrollment will continue to be affected by factors outside the control of sponsors, including systemic racism, historical mistrust in clinical research, healthcare inequities, and differences in health literacy.”
Importance of Continuing Medical Education
The Continuing Medical Education (CME) Coalition submitted comments in response to the draft guidance, emphasizing the importance of CME as a “key component of [the FDA’s] strategy to implement DAPs.” In the comments, the CME Coalition notes that importance of “greater inclusion of underrepresented populations” to lead to “better healthcare for all individuals.” The CME Coalition also noted that the FDA should partner with CME providers as they are “uniquely positioned to both identify and engage health care providers representing diverse backgrounds, perspectives, experiences, and patient populations, across a variety of disease states, to develop training that highlights the importance of recruiting diverse investigators and staff to increase diversity among clinical trial sponsors.” The CME Coalition concluded by saying, “collaboration between the FDA and CME providers is vital for the successful implementation of Diversity Action Plans in clinical trials.”