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Jill Wechsler reports on FDA's newly published strategies supporting broader eligibility criteria for Phase III studies.
A prominent goal for biopharmaceutical research has been to broaden the range of participants in clinical trials to fully assess the impact of new therapies on different ethnic, racial and age groups. FDA has pressed for more inclusive research programs for drugs and medical products for decades to enhance the understanding of how medications affect certain populations differently. An early aim was to reverse established limitations on testing new products on women and both very young and elderly patients. More recent policies aim to offset years of under-enrollment of minority groups by expanding enrollment criteria, including more research sites in minority communities, and engaging investigators with diverse backgrounds. The visibly high impact of COVID-19 on minority populations in the U.S. has focused added attention on the importance of including racial and ethnic minorities in clinical trials for pandemic vaccines and therapeutics.
Over the years, FDA has issued multiple guidance documents to encourage broader data reporting on research subjects of different races and ethnicities. In November 2020, the agency spelled out a range of strategies in a final document on “Enhancing the Diversity of Clinical Trial Populations.”1 It supports broader eligibility criteria for Phase III studies and outlines ways to make it easier for individuals to participate in clinical studies, such as utilizing adaptive trial designs and enrichment strategies to facilitate broader ethnic group participation.
The importance of more inclusive clinical trials, moreover, has been emphasized for developing drugs and biological products for combatting COVID-19, as seen in a broad guidance issued in May 2020.2 This advisory, which FDA staffers have augmented several times over recent months, supports a range of strategies for studying drugs and medical products during the pandemic, such as arranging for more decentralized clinical trials, fewer clinic visits, virtual check-ups, alternative monitoring processes, and remote data collection and informed consent processes. FDA extended these policies to early stage clinical trials and cites international standards for conducting diverse research developed under the International Council for Harmonization.
New vaccines to combat the pandemic similarly should test these critical products on a broad spectrum of patients, FDA advises in a June 2020 guidance that spells out regulatory expectations for assessing vaccine manufacturing processes and facilities and both nonclinical and clinical data. The agency specifies that to ensure that vaccines are safe and effective for all indicated populations, sponsors should enroll individuals most affected by COVID-19, specifically racial and ethnic minorities, elderly individuals and patients with medical comorbidities.3 And subsequent guidance published in October 2020 to clarify data requirements for requesting an Emergency Use Authorization (EUA) for a COVID vaccine notes the need for broad clinical data for a medical product intended to be administered to millions of individuals.4 The intense public focus on the conduct and results from vaccine clinical trials prompted sponsors to take steps to meet expectations in this area; some trials were even halted at times due to difficulties in attracting sufficient numbers of minority patients to participate.
FDA has also sought to promote research diversity through its Drug Trials Snapshots program, established in 2015 to increase the visibility of clinical trial enrollment by age, sex, ethnicity and race. Under this program, the Center for Drug Evaluation and Research (CDER) posts a brief “snapshot” on demographic participation in clinical trials for each newly approved new molecular entity and biologic therapy. According to a recent report on the program’s impact, though, there still may be a ways to go for clinical trials to reflect the diversity of the U.S. population. The analysis shows that while participation by sex has become evenly balanced in recent years, and sponsors are including more elderly patients, most studies still enroll relatively low percentages of black, Asian and Hispanic patients.5
The Snapshot report and related issues were discussed at a recent FDA webinar on Diversity in Clinical Trials.6 Richardae Araojo, FDA associate commissioner for minority health, noted that FDA’s November 2020 final guidance on increasing diversity in clinical trials supports the use of real-world data for identifying potential study participants and advised researchers to utilize strategies that may ease trial participation, such as local doctor visits to reduce lengthy travel. Sponsors need to plan early and engage diverse populations in trial design and site locations to establish inclusive study programs, Araojo advised. Trials should enroll the full range of patients likely to benefit from the new therapy, including those taking other medicines or with other medical conditions or obesity. And exclusion criteria should be limited to those factors related to risk of adverse events. To combat the pandemic, moreover, Araojo emphasized the importance of more inclusive clinical trials to reduce distrust of medical treatment by minority groups and offset vaccine hesitancy.