By James Miessler

The FDA has published overdue draft guidance on developing diversity action plans for clinical trials, moving the agency a step closer to the statutory mandate that all phase 3 trials include such plans.

The Food and Drug Omnibus Reform Act (FDORA), which Congress passed in December 2022, charged the FDA with requiring diversity action plans for certain late-stage trials and issuing draft guidance on the subject within a year of the bill being signed into law (CenterWatch Weekly, Jan. 2, 2023).

Though the agency missed that FDORA deadline by a wide margin, the draft guidance that arrived last week would start the clock on the requirement that sponsors submit diversity action plans for trials that begin enrollment 180 days after the draft’s finalization.

The 23-page guidance, which was announced by FDA Commissioner Robert Califf, offers sponsors recommendations on formatting, content, diversity goal development, submitting plans to the agency and publicly sharing action plans, as well as requesting waivers.

“This most recent update is more detailed in describing three required sections: enrollment goals, rationale for enrollment goals and measures to meet enrollment goals,” Sandy Smith, WCG’s senior vice president of clinical solutions and strategic partnering, tells CenterWatch Weekly. “With this publication, we are getting closer to understanding the required documentation and format for submission.”

Diversity action plans must lay out trial enrollment goals organized by race, ethnicity, sex and age group, according to the guidance. Sponsors should consider how the medical product’s intended use population is distributed according to these demographics.

In particular, think about whether certain populations, such as older patients, children, females or specific races/ethnic groups, might respond differently to the medical product. It’s also important to consider differences in disease presentation among different groups.

“In some cases, it may be necessary to increase the proportional enrollment of a certain population in the clinical study to evaluate outcomes of interest or other clinically relevant factors in that group,” the guidance notes.

On plan rationale, the FDA recommends sponsors include background information needed to understand the disease/condition at hand, including an overview of natural history and risk factors as well as prevalence/incidence estimates, if available, and rationale for having different enrollment goals across multiple planned studies supporting a single approval and how individual trials will support the overall enrollment goals of the clinical development program.

Diversity action plans should also detail how the sponsor intends to meet its enrollment goals through a description of enrollment and retention strategies. This part “should focus on specific measures that address the enrollment and retention of participants in the particular clinical study for which the diversity action plan is developed.”

In addition, plans should describe how sponsors will monitor their goals during trial conduct to help ensure targets will be met and enable swift action on addressing barriers as they appear.

For example, the sponsor could consider specifying “the manner and frequency with which study enrollment will be monitored (e.g., when a certain proportion of the study population has been enrolled), and any measures that may be undertaken should the sponsor determine that the study is not on track to meet enrollment goals,” the guidance reads.

The FDA encourages sponsors to seek patient and provider feedback when crafting these strategies.

The guidance provides a number of examples of potential enrollment and retention strategies:

• Sustained community engagement through advisory boards and navigators, community health workers, advocacy groups, local healthcare providers, community organizations, etc.
• Cultural competency and proficiency training for investigators and trial staff
• Improving participant awareness and knowledge of the trial, such as by providing language services for patients with limited English abilities
• Reducing participant burden by removing unnecessary trial-related procedures, imaging and lab tests; using convenient sites for procedures and lab tests; providing support on transportation and childcare; having flexible hours for study visits; and offering reimbursement
• Improving trial access by limiting exclusion criteria, selecting sites that have diverse populations and experience enrolling diverse participants and considering accessibility needs for patients with disabilities
• Using decentralized approaches “when appropriate”

While the FDA encourages sponsors to submit diversity action plans for drugs as soon as practical for the sake of efficiency (usually at the end-of-phase 2 meeting), they expect sponsors to file them no later than the date of protocol submission.

For devices, the plan must be included in the IDE application. Device studies that don’t require an IDE still would require a diversity action plan. In those cases, the plan should be attached as part of the device’s 510(k) application, premarket approval application or De Novo classification request.

Comments are due by Sept. 26.

Access the full draft guidance here.