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AgencyIQ — FDA just published its Diversity Action Plan guidance. Here’s what you need to know.

AgencyIQ — FDA just published its Diversity Action Plan guidance. Here’s what you need to know.

Quick background: FDA’s work to advance clinical trial diversity through prospective planning

  • The FDA has longstanding policy interests focused on research study diversity. The agency first issued guidance on demographic subgroup analyses in the 1980s. In the intervening years, FDA continued to update guidance in line with updates from the Office of Management and Budget (OMB) and Congressional directives. [ See AgencyIQ’s analysis for more detailed history of FDA’s policy and guidance on diversity in research studies].
  • In April 2022, the FDA  issued a draft guidance document on diversity in clinical research programs. At a high level, the guidance laid out a policy whereby sponsors of certain products would voluntarily submit a Race and Ethnicity Diversity Plan as part of their development program that would outline and justify their approach to recruiting and retaining a “representative” research population. [ Read AgencyIQ’s extensive analysis of the draft guidance here.]
  • At the end of 2022, as part of the 2023 Consolidated Appropriations Act, Congress gave the FDA new authority to require what the law referred to as Diversity Action Plans (DAPs) for certain clinical studies.  Section 3601 of the law amended the Federal Food, Drug and Cosmetic (FD&C) Act to expressly grant the FDA the statutory authority to require DAPs for 1) Drugs: for “a new drug that is in a phase 3 study” or “as appropriate, another pivotal study of a new drug (other than bioavailability or bioequivalence studies)”; 2) Medical devices: As part of an Investigational Device Exemption (IDE) submission or “for any clinical study.”
  • What do DAP submissions entail? DAPs are a plan, developed by the product sponsor, that would need to include specific enrollment goals, the rationale by which these goals were developed, and “an explanation of how the sponsor intends to meet such goals.” The statutory provision also allows for certain research programs to be exempted from the DAP requirement through a waiver system, which could be initiated by the FDA or “at the request of a sponsor.”
  • The law also directed the FDA to “update or issue guidance” on DAPs. Per Section 3602 of the Consolidated Appropriations Act, this guidance should include information about the specific format and content of the plans, such as the rationale for enrollment goals (e.g., estimated prevalence of the condition of interest, any relevant pharmacokinetic or pharmacogenomic data, demographic factors) and how they intend to meet those goals, as well as operational and process factors such as how they should be submitted and how the “action plan” may be updated over time.
  • The DAP guidance was required by the law to be published by the end of December 2023 – a  deadline that the FDA missedThe agency was  called out for missing the deadline by a prominent Democratic legislator, Rep. ANNA ESHOO (D-Calif.) at a Friends of Cancer Research event in February 2024. In response, regulators reiterated its importance and prioritization without committing to a specific time frame for publication.
  • That said, FDA has not done nothing in 2024 related to clinical trial diversity. In January 2024, the FDA  updated a 2016 guidance on the Collection of Race and Ethnicity Data. The new draft document, separate from the DAP guidance, offers recommendations for the standards for collecting and reporting race and ethnicity data in regulatory submissions. The FDA’s recommended approach continues to be based on the categories and frameworks outlined in OMB Directive 15, which defines the core set of minimum categories of race and ethnicity and offers recommendations on data capture. [ Read AgencyIQ’s full analysis of that draft guidance document here.]
  • In late March 2024, OMB finalized some long-awaited updates to Directive 15. Following an “ initial set of recommended revisions” from the  White House Office of the Chief Statistician in January 2023, Directive 15 has now been formally updated at the federal level. At a high level, this entailed  three main changes: (1) race and ethnicity are now  combined into one question; (2) Middle Eastern and North African (MENA) has been adopted as a new minimum category; and (3) the  Directive now “requires the collection of more detail beyond the minimum required race and ethnicity reporting categories” in most situations. [ Read AgencyIQ’s full analysis of the changes here.]

The DAP draft guidance has now been released

  • FDA Commissioner ROBERT CALIFF formally announced the new guidance at the  White House Clinical Trials Forum event hosted by the Office of Science & Technology Policy. On a panel focused on improving clinical trial access and participation, Califf offered some thoughts on the intended interpretation of the new draft guidance, saying: “Just reminding everyone that, you know, draft guidances are our ideas. They’re not binding, except in a few places where Congress has mandated that they are binding in terms of how you get the information to us. But the idea here is to gather knowledge, and then come out with a final guidance….” He further discussed his previous work in clinical trials, saying: “We did a lot of planning and simulation before we started it, but the diverse access to enrollment should be part of that plan. That’s really what we want to stimulate here, and we want people to tell us how are they planning to get the trial done and meet the criteria for in engaging and enrolling a diverse group of participants.”
  • The much-anticipated guidance is not a revised draft but rather a wholesale rewrite of the April 2022 guidance on diversity action plans. It does appear that FDA’s Oncology Center of Excellence (OCE), which wrote FDA’s original 2022 Draft Guidance, also took the lead with drafting the new guidance document; LOLA FASHOYIN-AJE (previously with OCE, and now at CBER’s Office of Therapeutic Products) is listed as the top point of contact on the guidance, along with TAMY KIM, who is OCE’s director for regulatory affairs and policy. The new draft guidance is listed as coming from FDA, OCE, CDER, CBER, CDRH and the Offices of Minority Health and Health Equity (OMHHE) and Women’s Health (OWH).
  • The new draft fulfills the FDA’s mandate from Congress to issue guidance on the format and content of the diversity action plans. Of note, while Section 3601 of FDORA did explicitly grant FDA authority to require sponsors to start submitting diversity action plans for certain studies, and provided a short list of what must be included in those submissions to FDA, it did not state that DAPs submitted by sponsors must address goals for clinical study enrollment “disaggregated by age group, sex, and racial and ethnic demographic characteristics of clinically relevant study populations.” Instead, these factors were included in the following section of the legislation (Section 3602) that directed FDA to issue guidance addressing what these plans would look like for sponsors’ goals for clinical study enrollment. Beyond these four categories, the law also gave FDA the ability to consider additional characteristics such as “geographic location and socioeconomic status” in the guidance on DAPs. While these factors were excluded from the April 2022 guidance, they are referenced throughout the new version.
  • How does the new draft guidance differ from the old draft guidance? While the 2022 OCE guidance was 12 pages, the new draft clocks in at 26 pages, including two pages of appendices that provide a summary of the elements FDA will expect in a DAP. Also included in the new draft guidance is the process for waiver requests, which were not addressed in the 2022 draft guidance document.
  • The new DAP draft guidance goes over the process, content and procedures for DAPs. It opens with a discussion of the agency’s work so far on enhancing diversity in research populations, and key areas of consideration for defining diversity. The guidance goes over the top lines of a DAP, including how to set, justify, and measure progress against enrollment goals. The guidance also covers the operational processes for DAPs, including how and when to submit them (and modify them), and how to request a waiver. As noted above, the guidance includes a fairly short appendix that lists a summary of the requirements elements of a DAP.
  • A quick note up front: What does “underrepresented” mean? Per the new draft guidance, and specifically footnote 10: “this guidance focuses on underrepresented populations based on race, ethnicity, sex, and age group, but FDA notes that there are other underrepresented populations that sponsors may consider, such as pregnant or lactating individuals…. Generally, for race and ethnicity, underrepresented populations may typically include participants who are Black or African Americans, Hispanic/Latinos, Indigenous and Native American, Asian, Native Hawaiian and Other Pacific Islanders, and other persons of color. Generally, for sex and age, underrepresented populations may typically include participants who are females and in the older adult and pediatric age groups, respectively.”
  • In a later section, the agency goes on to note that while the guidance focuses on diversity in “different age groups, sexes, and racial and ethnic demographic characteristics,” the agency also “recognizes the broader issues regarding health disparities and differential access to health care and clinical studies that may occur based on other factors, including but not limited to geographic location, gender identity, sexual orientation, socioeconomic status (SES), physical and mental disabilities, pregnancy status, lactation status, and co-morbidity. As applicable, FDA encourages sponsors to consider such additional factors, which may support subgroup analyses, when developing Diversity Action Plan enrollment goals.”
  • In short: The guidance focuses on DAPs for adequate representation in four domains, namely race, ethnicity, age, and sex. For the purposes of approaching populations that are “underrepresented” in clinical research, this means participants that are Black or African American, Hispanic/Latino, Indigenous and Native American, Asian, Native Hawiian and Other Pacific Islanders, and “other persons of color,” as well as women and older or pediatric age groups. Sponsors are “encouraged” to consider other demographic categories and factors, such as SES or disability status, to support subgroup analyses, but that’s not the primary focus of this guidance. Notably, section 3602 of FDORA does specifically state that the “format and content” of DAPs “required” under the new statutory authority should be focused on these four domains (race, ethnicity, age, sex), but that they also “may include characteristics such as geographic location and socioeconomic status.”

First up: Who needs a DAP, how are they submitted, can they be modified, and where do they go?

  • For drugs, the DAP authority is at 505(z) of the FD&C Act. Per that statutory requirement, “a Diversity Action Plan is required for a clinical investigation of a new drug that is a phase 3 study (as defined in 21 CFR 312.21), or as appropriate, another pivotal clinical study of a drug (other than a bioavailability or bioequivalence study).”
  • For drugs, DAPs should be submitted to the relevant IND is “as soon as practicable but no later than the date on which the sponsor submits the protocol to FDA for the phase 3 study” or other pivotal study. In order to give the agency time to give feedback on the DAP, it goes on to recommend DAP submission “when the sponsor is seeking feedback regarding the applicable clinical study for the drug (typically at the End-Of-Phase 2 meeting).” Progress under the DAP will need to be included in the annual reports for the relevant IND.
  • For drugs, submissions and getting feedback and marketing applications: The agency recommends that DAPs should “generally not excee[d] 10 pages, excluding references,” and should remain as succinct as possible with “limited cross-referencing.” As noted above, DAPs for drug products will be submitted to the relevant IND (and if that IND is in eCTD format, then the DAP should be as well, in module 2.5), and the plan should include information about that IND (drug name, IND number, study identification number). DAP submissions will need to include a cover letter alerting the agency of whether it is “Initial” or “Revised,” and should flag any relevant waivers (see below). Depending on the specifics of the program, agency reviewers may or may not provide feedback, with feedback given “at FDA’s initiative or per the sponsor’s specific request for feedback.” Sponsors can modify the DAP over time, but will need to include a tracked-changes version of the DAP and a “summary of modifications and justification” section. Information about the DAP and any modifications, waivers, or other updates should be included as regulatory history for milestone meetings. In marketing applications, sponsors will need to provide “a brief overview” of the DAP and an assessment of whether goals were met, as well as any information about waivers; this should be included in module eCTD 2.5.
  • For devices, the DAP authority is at 520(g) of the FD&C Act. That statutory requirement for a DAP is based on the applicability of the Investigational Device Regulations (IDE). For both medical devices for which an IDE application is required as well as those for which an IDE is not required but from which the IDE regulations are not exempted, then a DAP may be required. Specifically, the statute states that DAPs should be developed for any device for which an IDE application is required under current policy, as well as for devices “for any clinical study” that does not require an IDE, except for those that are IDE exempted. In effect: DAPs are required, under statute, for a device that is significant risk (SR) under the IDE regulations (and therefore needs an IDE application), those that are non-significant risk (NSR) under the IDE regulations (and do not need an IDE application), but not for those that are IDE exempt.
  • The guidance provides some granularity on DAP applicability to non-IDE studies. The guidance notes that clinical studies that are “designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use” will be those subject to the DAP requirements, regardless of whether an IDE is required. For these products, DAPs must be submitted as part of the pre-market request (i.e., 510(k) pre-market notification, De Novo request, or Pre-Market Approval (PMA) application), and include information both about the DAP and its final results (e.g., whether enrollment targets were met). Further, FDA recommends “that sponsor provide a clear and concise description of the Diversity Action Plan for inclusion in the public-facing summary documents.”
  • The agency “acknowledges that a Diversity Action Plan may not be particularly meaningful for certain device studies, such as for small studies conducted during the exploratory clinical state. Notwithstanding this point, FDA expects sponsors to develop a Diversity Action Plan for a study that is intended to serve as the primary basis for FDA’s evaluation of safety and effectiveness and benefit-risk determination.” However, IDE-exempt studies (those exempt under 21 CFR 812.2(c), such as many diagnostic products) do not need a DAP, “regardless of whether it is intended to service as the primary basis for FDA’s evaluation and safety and effectiveness and benefit-risk determination.”
  • The formatting expectations for a device DAP are the same as those for drug products, specifically that they should be “generally not exceeding 10 pages, excluding references,” and “with limited cross-referencing to previously submitted documents.” Further, they should include a cover letter alerting the agency of the DAP (and whether it’s initial or revised or there is any wavier in place), with “relevant administrative information” indicated on the title page, such as the device name and relevant submission number.
  • Device DAP submissions: For products that require an IDE, the DAP should be submitted as part of the IDE application. For those that do not require an IDE but are subject to the DAP requirement, the DAP should be submitted as part of the marketing submission, but the agency notes that it “encourages sponsors” to seek agency feedback, potentially via a pre-submissions (Q-submission program); although it does note that “FDA anticipates that many Diversity Action Plans for studies not requiring submission of an IDE application may be developed without FDA’s input.” Interactions with the agency – from marketing submission and IDE application to requests for feedback or meetings – should include “a summary of any discussions and correspondence” about the DAP, including any waiver information.
  • Specifically for studies under an IDE: As with the IND requirements, annual reports under IDEs will need to include updates on the DAP. Marketing submissions with data from studies under an IDE will need to include “a brief overview” of the DAP and the study’s performance under its DAP (e.g., whether enrollment goals were met).
  • Device DAPs can also be modified, again (like drug DAPs) “based on feedback form the FDA or at the sponsor’s own initiative”) and include tracked changes and a clean version with a “Summary of Modification and Justification” section. However, the process for modifications varies. If the DAP was submitted with an IDE application, then “FDA considers changes to the Diversity Action Plan included in an approved IDE to be similar to other types of changes made to the approved study,” and sponsors should follow existing practices for making changes to a study under an approved IDE application (for example, determining whether a change requires a 5-day notice or can be implemented and then subsequently included in the annual report). For modifications to a DAP under a study that is intended to support the FDA’s evaluation of the device but did not require an IDE, the sponsor can submit a pre-submission to get feedback on the modification – but, again, “FDA anticipates most modifications to a Diversity Action Plan for studies that do not require an IDE will not require feedback from the Agency.”
  • And finally: “Posting of key information.” The draft guidance includes a short section at the end “strongly encourage[ing] sponsors to share strategies for meeting Diversity Action Plan enrollment goals with the public,” including key information about enrollment goals and measures taken to meet those goals. This would be included in the same way that “other content” regarding investigational or non-authorized products are on a public website “(e.g., on the “pipeline” page of a sponsor’s website)” in consumer-friendly language.

Designing a DAP: Setting, justifying, and measuring progress

  • This is a key section of the guidance: As AgencyIQ has discussed, early experience with the voluntary diversity plans under the 2022 guidance saw sponsors struggling with how to set enrollment goals. Per data presented in December 2023, about 90% of the feedback from FDA so far on those voluntary plans was focused on enrollment goals, although feedback on enrollment monitoring and strategies to enhance accrual to meet those goals have also been common occurrences so far (29% each). In the new DAP guidance, industry had been hoping for more granular advice on how to set enrollment goals.
  • First up: Setting enrollment goalsEnrollment goals under a DAP would need to be broken down by demographic groups (see Table 1). As in the 2022 draft guidance, the new draft guidance states that “increased enrollment (i.e., greater than proportional) of certain population may be needed” in order to assess differential responses or “potential clinically important differences.”
  • What about programs with multiple studies? The new DAP guidance goes into more detail about research programs with “several clinical studies” that are subject to DAP requirements. For these programs, “the sponsor’s enrollment goals…for each study should consider how individual clinical studies may fit into an overall clinical development program” and how the individual studies would generate data “consistent with the incidence or prevalence in the disease population for the program.” In general, the multiple studies within the research program should, when consider together, represent “an overall proportionate representation, even though individual studies may not have proportionate representation.” In effect, not all individual studies in a research program need to reflect the U.S. incidence/prevalence, but all together they should be representative.
  • What about rare diseases? Rare disease programs may have the opposite problem, with just “a single, small pivotal study.” The agency notes that “despite enrolling a representative population in that study,” there may not be sufficient power in the sample size to detect differences across demographic groups, “should they exist, or limiting the sponsor’s ability to conduct a robust assessment of observed differences.” However, the agency goes on to note the importance of DAPs for rare disease studies – particularly, “future study or hypothesis generation.”
  • Methods for considering the “population” prevalence: As noted above, estimated incidence/prevalence should “generally inform enrollment goals.” The agency cites several potential sources for identifying the population-level incidence or prevalence across different demographic groups, including registries or published literature, as well as non-public sources (e.g., certain registries or electronic health data) – although the latter will need to be described to the agency. When there is no clear source of data on the population level or demographic characteristics of the intended population, the agency offers a couple of options. First, if the sponsor is considering a narrower indication (intended use population) for a specific subset of a disease or condition, “it may be acceptable to use prevalence and incidence information for the broader disease” and base demographic considerations off of the broader population, rather than the narrower indication. Second, if the product would be intended for the general use population, the sponsor can use the demographic information about the U.S. overall (i.e., census data). Finally, if there is limited or no information on how to characterize the demographics of an intended use population, sponsors may again use the general U.S. population demographics.
  • What about global programs? Again, questions about the impact of the DAP policies on global development programs have been flagged as key questions, and challenges, for sponsors working under the voluntary diversity plan guidance. In effect, with the FDA asking sponsors to reflect the U.S.-specific intended use population, this presents “apparent tension between long standing practices of accepting foreign data to expedite drug development and a new emphasis on diversity and representativeness in clinical trials,” Fashoyin-Aje has acknowledged. The draft guidance offers some information for how to think about DAPs under “multi-regional clinical studies,” including “globally conducted clinical development programs.” The DAP for a multi-national study should include all participant enrollment goals, “and should not be limited to the U.S.-enrolled participants,” and will need to account for the DAP requirement to enroll a U.S. representative population. While the agency “recognizes that the lack of uniformity across the globe” in domains like the definition of race and ethnicity “may pose challenges,” it does not offer additional guidance on how to account for these challenges beyond noting that sponsors “should engage early with review divisions” to talk about geographic challenges.
  • Next, providing the rationale for enrollment goals: For both drugs and devices, DAPs need to include a sponsor’s rationale for the enrollment goals they’ve set (as described above). The new draft guidance offers some baseline parameters that should be addressed in these justifications, including background information on the disease (including incidence and prevalence estimates, if they’re available) and information about how different enrollment goals across different clinical studies “are intended to contribute to the overall enrollment goals” for the whole program. For drug products, the rationale should also address any data “that suggest a potential for differential safety and effectiveness” of the drug, such as PK/PD differences, different genetic variations that could impact metabolism, or other “population-level or individual characteristics” (e.g., SES, geographic location) that could impact clinical outcomes. For devices, sponsors should include any data that could inform goals related the potential for differential safety or efficacy, and any available data about how demographic differences could be tied to these differences as well as characteristics like SES or comorbidities. The device section also calls on sponsors to include information on “relevant factors for device performance (e.g., phenotypic, anatomical, technological, or biological factors)” that could lead to differential effects across different demographics and how these data were considered in enrollment goals. The guidance specifically cites the example of variations in skin pigmentation that could “affect the performance of certain devices.”
  • Your plan to meet enrollment goals: Measures. The DAP will need to include information about how the sponsor intends to meet the enrollment goals as laid out, including “a description of the enrollment and retention strategies for the study population.” This section of the DAP should focus on the different activities that sponsors will invest in to recruit and retain historically underrepresented population as per their enrollment goals, such as “sustained community engagement,” cultural trainings for investigators and research staff, methods to increase patient awareness and knowledge of study opportunities, methods to reduce patient burden, improving access to the study (physically or via limited exclusion criteria) and “employing clinical study decentralization when appropriate.” The DAP should include the sponsor’s monitoring plan, and what efforts the sponsors would employ “should the sponsor determine that the study is not on track to meet enrollment goals.”

Requesting a waiver: Process and potential

  • The statutory authority for DAPs includes the possibility of a wavier from the requirements. As the agency described in the guidance, the FDA may “waive the requirement to submit a Diversity Action Plan, or any part thereof” – in effect, a full waiver from the DAP requirements, or a partial waiver from specific DAP requirements.
  • Statutory wavier criteria include: (1) if a wavier is necessary “based on what is known or can be determined about the prevalence or incidence” of the condition; (2) conducting the investigation with a DAP “would be otherwise impractical”; or (3) “a waiver is necessary to protect public health during a public health emergency.”
  • The guidance, however, focuses on reasons why you wouldn’t get a waiver: Per FDA, “full or partial waivers from [the DAP requirements]… will only be granted in rare instances,” it cautions – and recalling recent statements made by guidance co-author TAMY KIM at last week’s Drug Information Association Annual Meeting. The guidance goes on to note that the agency does not expect to grant waivers “even if the disease or condition under study is relatively homogenous,” and cites the need for broader enrollment of historically underrepresented populations as the key driver for the policy.
  • The process for a waiver: For drugs, waivers should be submitted electronically in eCTD module 1.12.5 (Request for Waiver) to the IND, with an accompanying cover letter identifying the waiver request. For devices, waiver requests are standalone submissions, which should include “submission number(s) if available, information about the device including a device description and proposed intended use, the applicable clinical study, the type of marketing submission that the clinical study is intended to support, and a justification for the waiver request, including relevant data and information.” The FDA must issue a written response (denying or granting) “within 60-days of receiving such a request,” and therefore urges early interaction with the agency due to the relatively quick turnaround time. Specifically, “Sponsors should request a waiver early enough to allow sufficient time for preparation and submission of the Diversity Action Plan as required, should FDA deny the waiver request. Sponsors should not submit waiver requests less than 60 days before the Diversity Action Plan is required.”
  • One quick note: In circumstances when the FDA itself determines that wavier is required (e.g., in case of a public health emergency), then “FDA will notify interested parties through appropriate channels” – such as through its website or “public communications.”

What’s next? A comment period and a final guidance

  • The new draft guidance differs slightly from the approach outlined in the 2022 OCE guidance. The 2022 guidance stated that enrollment goals should be partially derived from the “pre-specified protocol objectives of the investigation” as well as an initial assessment performed by the sponsor on whether there might be differences in drug/device performance for racial/ethnic patient subgroups. The new guidance takes a different approach – It directs sponsors to set enrollment goals using data about the incidence and/or prevalence of a disease in the U.S. population. In other words, it doesn’t direct sponsors to first consider existing evidence on potential differences in product safety/efficacy and then use that info to set enrollment goals. Instead, it instructs the establishment of enrollment goals based on the composition of the underlying patient population. Only after the demographics of a patient population have been established, should sponsors consider next whether there is data to indicate potential differences in a product’s safety/efficacy by patient subgroup. If so, this data would be used to adjust enrollment goals, likely so that subgroup analyses are sufficiently powered to detect potential differences in outcomes or side effects by subgroups should they occur. Furthermore, the new guidance describes this second step as constituting the rationale for proposed enrollment goals, underscoring its use as a contextual feature rather than core component of setting enrollment goals.
  • The DAP requirement applies for clinical studies “for which enrollment commences after 180 days from the publication of the final guidance.” Per the FDORA bill text, the final guidance is due “not later than 9 months after closing the comment period on such draft guidance.” Notwithstanding that the agency blew past the 12-month timeline for issuing the draft guidance by about six months, with the 90-day comment period on the draft guidance, this would theoretically put the guidance into force in late December 2025. Notably, this back-of-the-calendar math assumes that the current comment period (open through September 26, 2024, according to the guidance landing page, although the guidance has not yet been formally published in the Federal Register) will not be extended, and that the FDA will meet the statutory timeline for finalizing the guidance within nine months of the closing of the comment period.
  • There agency is offering some flexibility in the actual implementation, however. The agency, acknowledging that sponsors plan for and implement study activities “prior to when enrollment commence,” said it “does not expect” a DAP for certain projects. Specifically: (1) when a drug product’s protocol is submitted “within 180 days” after a final guidance is published and in which enrollment will begin in the 180 days (i.e., during the implementation period); (2) device studies for which an Investigational Device Exemption (IDE) is received within 180 days of the publication of the final guidance; and (3) device studies for which an IDE is not required but which are approved by an institutional review board (IRB) or independent ethics committee (IEC) within 180 days of the final guidance publication. Still, this is a tight timeline for industry, in which clinical studies are planned out well in advance.
  • The guidance offers some more recommendations for industry on how to find appropriate sources for enrollment goals, including deferring to the U.S. general population demographics when appropriate or if there is limited to no information about the expected intended use demographic breakdown.
  • The question of waivers: As noted above, FDA officials have recently been cautioning industry that they expect waivers to be rare; however, the way this works out in practice (including certain “partial” waivers, depending on the information that is available about certain demographic groups) remains to be seen. The guidance notably doesn’t offer different potential models of a partial waiver, but presumably these would include waivers from specific requirements under the DAP policies.
  • A key complexity for industry: Implementation and measures. The guidance itself acknowledges in several places that there are circumstances beyond the control of the life sciences industry (or the FDA) that impact whether or not different populations may be eligible to participate in research studies, including the accessibility of health care in their area (e.g., White patients are more likely to be screened for certain cancers, higher-SES populations are more likely to access preventive care or undergo testing, rural patients are less likely to have diagnostic laboratory services or specialty medical providers available to them). The guidance generally indicates that the intent is for life sciences product sponsors to invest in community-facing strategies to ensure diverse populations in their research studies, such as cultural competency training for investigator staff and partnerships with patient populations. However, whether those methods are sufficient to suitably enroll and retain new research populations also remains to be seen, or if different therapeutic areas will face bigger challenges in this area than others, and how/if FDA’s policies will adapt from there.
  • A key question not answered here: What happens if targets aren’t met? The 2022 draft guidance from OCE included the following language: “In the event that recruitment goals are not met despite best efforts, sponsors should discuss with FDA a plan to collect this data in the post-marketing setting” (footnote 24). The new DAP guidance, however, includes no such caveat. This is likely to be a key point of consideration and feedback from industry.