Key Takeaways

  • FDORA's DAP mandate is law — the statutory requirement survived the January 2025 guidance removal and February court-ordered restoration. Sponsors must comply regardless of guidance status.

  • Site selection is the dominant lever. J&J's AI-driven geospatial platform produced a 3x enrollment lift in top-ranked sites across ~50 trials (J&J Health for Humanity Report, 2022; PharmaVoice, 2023).

  • Community infrastructure investment is accelerating. Sanofi committed $18M to three HBCUs; BMS committed $124.5M to diversify trial pipelines (Fierce Biotech, 2025; BMS Foundation, "Excellence in Clinical Trials").

  • The accountability gap is real. Congress mandated DAP submission but not public disclosure. Only 14% of protocols explicitly include diversity considerations (Applied Clinical Trials, October 2025).

  • The barrier is access, not willingness. A meta-analysis found >50% of offered patients agreed to enroll — the system fails to reach them, not to convince them (PMC, 2022).

The Regulatory Landscape: A Mandate in Limbo

FDORA Section 3601 requires sponsors to submit Diversity Action Plans for most Phase 3 and pivotal studies. The FDA's June 2024 draft guidance specified six components: enrollment goals, justification, recruitment strategies, retention strategies, monitoring and reporting, and site selection considerations (FDA Draft Guidance, June 2024).

The timeline since then has been unusual. The FDA issued draft guidance in June 2024 and closed comments by September. In January 2025, the agency removed the guidance from its website after an executive order curtailing DEI programs (Crowell & Moring, 2025). By February 2025, the guidance was restored by court order — but with an administration memo suggesting portions be disregarded (LeapCure, 2025). The statutory deadline for finalization remains June 2025.

The statutory requirement remains law regardless of the guidance document's fate. Sponsors face a mandate whose implementing details remain in flux — but whose legal force does not.

Site Selection: The Primary Strategic Lever

Across public disclosures, one theme dominates. Sponsors treat site selection as the highest-impact intervention for enrollment diversity.

J&J's AI/geospatial platform applies machine learning to de-identified real-world data, mapping where eligible patients are located and ranking sites by diversity enrollment potential. The results: top-50% sites enrolled 3x more patients than lower-ranked sites. The platform is deployed across ~50 trials (J&J Health for Humanity Report, 2022). By end of 2023, 84% of J&J's actively recruiting studies (31/37) were on track with diversity goals. In five multiple myeloma studies, enrollment of Black patients exceeded twice the historical industry average (J&J, 2023; PharmaVoice, 2023).

J&J was one of the first companies to voluntarily submit DAPs after the 2022 draft guidance — the clearest example of a sponsor treating this as an operational challenge rather than a compliance exercise.

The community site shift is the second major pattern. Traditional clinical trial infrastructure — concentrated in large academic medical centers in major metros — structurally limits who participates. The investments here are significant.

Eli Lilly launched its Equitable Breakthroughs in Medicine Development initiative, explicitly shifting research toward community-oriented settings (Lilly, 2024). Sanofi invested $18M in 2024 into clinical research infrastructure at three HBCUs (Fierce Biotech, 2025). BMS committed $124.5M — $100M from the BMS Foundation plus $24.5M from funding partners — to diversify their trial pipeline and expand community site capacity (BMS Foundation, "Excellence in Clinical Trials").

The Emerging Lifecycle Framework

A 2023 practical guide in Contemporary Clinical Trials offers one of the most detailed public frameworks for operationalizing diversity across the trial lifecycle — developed through cross-disciplinary collaboration spanning clinical operations, health economics, medical affairs, patient advocacy, and R&D (Contemporary Clinical Trials, 2023).

Planning: Review eligibility criteria for unnecessary restrictions. Engage patient advocacy early. Build community feedback loops before the protocol is finalized.

Startup: Site and investigator selection aligned to diversity goals. Demographic target-tracking systems established from day one.

Ongoing: Real-time monitoring against benchmarks. Built-in mechanisms to adjust recruitment strategies if enrollment falls short of targets.

Closeout: Document learnings. Strengthen community partnerships for future trials. Capture what worked and what didn't.

This is a meaningful evolution. Historically, diversity was an afterthought — flagged during regulatory review, not embedded in trial design. The lifecycle approach makes it operational infrastructure.

Enrollment Target-Setting: The Hardest Problem

How sponsors set diversity targets is the most consequential — and least publicly documented — aspect of DAP development.

The FDA's draft guidance specifies targets should reflect the "clinically relevant population": disease-specific epidemiology, not census proportions (FDA Draft Guidance, June 2024). A sickle cell trial and an Alzheimer's trial will have fundamentally different targets because their disease demographics differ.

J&J has offered the most visibility here, describing a framework integrating disease prevalence data, national demographics, and historical recruitment patterns. They applied it to 18 studies across immunology, cardiovascular, and oncology (J&J, 2023; PharmaVoice, 2023).

The "clinically relevant population" standard creates a meaningful analytical burden — sponsors must do the epidemiological homework for each indication. But it also ensures targets are scientifically grounded rather than arbitrary.

Decentralized Trials: Promise With a Critical Caveat

Remote monitoring, telemedicine, and home visits reduce geographic barriers. The appeal for diversity is obvious. But recent research in Nature Medicine raises an important counterpoint: decentralized approaches can worsen disparities when designed without attention to digital access gaps (Nature Medicine, 2024).

Rural internet limitations. Varying digital literacy among older adults and low-income populations. Technology-forward trial designs that inadvertently exclude the populations they aim to include.

The implication is straightforward: decentralized elements complement physical infrastructure in underserved communities. They do not replace it. Technology is a tool, not a strategy.

Investigator Diversity Drives Participant Diversity

The data here is striking and underappreciated. Fewer than 5% of U.S. academic faculty are African American. Only 3% are Hispanic. Female lead authors comprise just 17.9% of oncology trial publications (PMC, 2022).

This matters because diverse investigator teams correlate directly with increased minority enrollment. Female-led heart failure trials showed 50% higher female participation compared to male-led trials. The mechanism is likely multifactorial — different site selection, more inclusive protocols, stronger trust-building with underrepresented communities. Workforce composition is not a secondary consideration. It is a primary driver of enrollment composition.

Community Engagement: Access, Not Persuasion

Several sponsors have moved beyond recruitment advertising toward genuine community partnership.

Sanofi co-founded a grassroots collective of 30+ organizations — patient advocacy groups, sponsors, sites, and community partners — with Atlanta as the first pilot (Sanofi).

The barbershop trial: A hypertension study met Black men in familiar, trusted environments. Result: 300+ participants recruited, 95% retention (PMC, 2022).

The meta-analysis finding: >50% of patients offered clinical trial enrollment agreed to participate (PMC, 2022).

The gap is not willingness. The gap is the system's ability to reach patients. If the infrastructure and trust exist, enrollment follows. This reframes the entire diversity challenge — from a persuasion problem to an access problem.

What We Still Cannot See

The accountability gap remains the central tension. We can see general sponsor diversity commitments, aggregate historical enrollment data, dollar commitments to initiatives, and the FDA's aggregate annual report to Congress. We cannot see individual DAP documents, trial-specific enrollment targets by race or ethnicity, FDA feedback on submitted plans, cross-sponsor or cross-therapeutic-area comparisons, or enforcement actions.

Only 14% of clinical trial protocols explicitly include diversity considerations (Applied Clinical Trials, October 2025). The most recent comprehensive demographic data from 2020 shows persistent gaps: 8% Black versus 14.2% census, 11% Hispanic versus 18.7%, 6% Asian versus 7.2% — across 32,000 U.S. drug trial participants (PMC, 2022).

FDORA created a mandate without creating transparency. Academic commentators have called for mandatory public disclosure of DAPs through ClinicalTrials.gov, enforcement mechanisms for unmet enrollment goals, and expanded product labels with representation data from the development program (PMC — The Promise and Perils of Diversity Action Plans, 2024).

The Strategic Direction Is Clear

The leading sponsors have moved well beyond performative commitments. The investments are real — AI-driven site selection, community infrastructure, workforce development, operational frameworks embedding diversity across the trial lifecycle.

But the industry is deeply uneven. J&J leads in transparency and early compliance. Others publish commitments without disclosing specifics. The regulatory environment remains caught between a statutory mandate and shifting political winds.

For sponsors preparing DAPs, the playbook emerging from publicly available evidence:

  • Site selection → AI/geospatial tools to match sites with diverse patient populations

  • Community infrastructure → invest in non-academic sites where underserved populations access care

  • Enrollment targets → ground in disease-specific epidemiology, not census proportions

  • Monitoring → real-time tracking with built-in course correction

  • Investigator workforce → diverse PIs drive diverse enrollment

  • Decentralized elements → complement physical access, don't replace it

The companies treating this as a scientific and operational challenge — rather than a compliance checkbox — will be best positioned regardless of how the guidance lands.

Sources