TL;DR: On 15 December 2025, the FDA issued guidance for industry titled Enhancing Participation in Clinical Trials — Eligibility Criteria, Enrollment Practices, and Trial Designs. It tells sponsors to justify, rather than default to, restrictive eligibility criteria at every phase of drug and biologic development — covering both demographic factors (age, sex, race, ethnicity, geography) and non-demographic factors (organ dysfunction, comorbidities, disability, weight extremes, HIV status, low-prevalence conditions). This is a distinct document from, and broader in scope than, the FDA Diversity Action Plan requirement created by FDORA — see the comparison below.
What the guidance covers
According to FDA’s guidance-document listing and law-firm and trade-press coverage tracking the release (King & Spalding, ClinicalLeader, Targeted Oncology), the December 2025 guidance addresses how sponsors of trials intended to support a new drug application (NDA) or biologics license application (BLA) design eligibility criteria and enrollment practices. Its central recommendation is that exclusion criteria should be scientifically or clinically justified rather than inherited by default from prior protocols or applied for convenience. Specific recommendations reported across this coverage include:
- Eliminating overly restrictive Phase 2 exclusion criteria unless there is a clinical or scientific rationale for keeping them — a notable departure from the common practice of using tighter eligibility criteria in early-phase studies and loosening them later.
- Avoiding unnecessary exclusion of participants on the basis of older age, weight extremes, HIV status, or disability, unless the exclusion is justified by a genuine safety or scientific concern specific to the study drug.
- Considering non-demographic population characteristics explicitly in trial design — organ dysfunction, comorbid conditions, and populations with diseases or conditions of low prevalence — not just the demographic breakdowns (age, sex, race, ethnicity) that dominated the diversity conversation in FDA policy through 2024.
- Enrolling participants whose demographic characteristics reflect the population expected to use the drug if approved, consistent with the generalizability rationale FDA has applied across its recent diversity- and inclusion-related policy work.
Because FDA’s own guidance-document page for this title returned a 404 on direct verification during drafting — a recurring issue with FDA’s guidance-document URLs generally, also seen with the Diversity Action Plan guidance — the specifics above should be treated as REPORTED-tier: corroborated across multiple independent secondary sources rather than confirmed against FDA’s primary document text directly. Sponsors relying on this page for compliance decisions should locate and read the guidance document itself via FDA’s guidance document database.
How this differs from the FDA Diversity Action Plan requirement
It’s easy to conflate this guidance with FDA’s Diversity Action Plan (DAP) requirement, since both concern who gets enrolled in clinical trials and both were issued by FDA within roughly the same policy window. They are not the same thing, and a sponsor can be fully compliant with one while the other is irrelevant to a given study:
- Legal basis and bindingness. The Diversity Action Plan requirement is a statutory mandate — created by Section 3601 of the Food and Drug Omnibus Reform Act (FDORA) of 2022, codified as FDCA Section 505(z) for drugs/biologics and Section 520(g)(9) for certain devices. The December 2025 eligibility-criteria guidance is non-binding guidance for industry: it states FDA’s current thinking and recommended approaches, not a statutory submission requirement.
- What sponsors must produce. The DAP requirement obligates covered sponsors to submit an actual named document — enrollment goals broken out by age, sex, race, and ethnicity, plus rationale and an operational plan for meeting the goals. The eligibility-criteria guidance does not require a standalone submission; it shapes how sponsors write and justify eligibility criteria within the protocol itself.
- Which studies are covered. DAP obligations attach specifically to pivotal studies supporting a marketing application — Phase 3 (or FDA-agreed pivotal) studies for drugs and biologics, and IDE/510(k)/De Novo/PMA studies for devices. The eligibility-criteria guidance is framed across the development lifecycle, explicitly reaching Phase 2 exclusion-criteria practices that the DAP requirement does not touch.
- Scope of population characteristics. DAP goals are demographic only — age group, sex, race, ethnicity. The eligibility-criteria guidance explicitly extends to non-demographic characteristics: organ dysfunction, comorbidities, disability status, weight extremes, and low-prevalence conditions.
In practice, the two are complementary: a sponsor building a DAP for a pivotal trial should be applying the same generalizability logic the eligibility-criteria guidance recommends when it decides which exclusion criteria are actually necessary earlier in that same program. See the full FDA Diversity Action Plans for Clinical Trials guide for the DAP requirement itself, including which studies are covered and the current status of FDA’s DAP-specific implementing guidance.
What it means for sponsors and research teams
For research administrators and clinical operations teams, the practical shift is at the protocol-design stage, earlier than where DAP obligations bite. Eligibility-criteria review should now document a rationale for each exclusion criterion, particularly ones inherited from a prior-phase protocol or a similar program, rather than carrying them forward by default. This intersects with existing patient retention and patient engagement practice, and with site selection decisions, since criteria that unnecessarily exclude older patients, patients with comorbidities, or patients from a narrow geographic catchment also narrow the pool of sites and populations that can feasibly enroll.
Frequently asked questions
Is this guidance legally binding on sponsors?
No. FDA guidance documents, including this one, represent the agency’s current thinking and recommended approach; they do not have the force of law the way a statute or regulation does. FDA can still raise eligibility-criteria design as a review concern during an IND or marketing-application review, which gives the guidance practical weight even though it isn’t a binding rule.
Does this guidance replace the Diversity Action Plan requirement?
No. The DAP requirement remains a separate, statutory obligation under FDORA for covered pivotal studies. This guidance addresses eligibility-criteria design more broadly and does not eliminate or substitute for the DAP submission requirement where it applies.
Does this guidance apply to device studies?
Coverage reported in secondary sources for this guidance centers on trials intended to support an NDA or BLA — drugs and biological products. Confirm applicability to a specific device program directly against FDA’s guidance-document text or with regulatory counsel; this page should not be treated as authoritative on device-specific scope.
Sources
- FDA, guidance document listing (title verified via search; full text not independently retrievable at time of writing) — FDA Guidance Document Database
- King & Spalding, “FDA Issues New Guidance for Enhancing Participation in Drug Clinical Trials” — kslaw.com
- Clinical Leader, “FDA Issues Final Guidance On Clinical Trial Participation” — clinicalleader.com
