New FDA Guidance: Further Enhancing Clinical Trial Participation

In December 2025, the U.S. Food and Drug Administration (FDA) released a new guidance focused on improving participation in clinical trials. The guidance provides updated recommendations to increase patient enrollment among representative populations in clinical research. Its goal is to ensure that clinical trials for drugs and biologics reflect the real-world populations likely to use these therapies after approval, taking into account demographics as well as factors such as comorbidities, disabilities, and rare diseases.

Below is a breakdown of the key recommendations outlined in the new FDA guidance.

1. Broaden eligibility criteria.

When determining who can participate in trials, the FDA recommends avoiding unnecessary exclusions, such as those related to older age, weight extremes, HIV status, or disabilities. It also recommends that researchers make justifications for any exclusions based on safety or scientific rationale. The guidance also encourages sponsors to reassess restrictive eligibly criteria carried over from early-phase trials when designing later-phase studies. Overall, trials should aim to include a diverse range of participants across age, sex, race, and ethnicity to enable more meaningful subgroup analyses.

2. Trial design approaches.

The FDA encourages the use of adaptive designs that allow study populations to expand as safety data becomes available, while applying prognostic and predictive enrichment strategies that preserve demographic diversity rather than limit it. Sponsors are also encouraged to characterize drug metabolism early to minimize the need for exclusions later in development. Inclusive pediatric programs should be planned, and pregnant participants should be considered when appropriate and safe to do so.

3. Reduce participation burden.

Trials can better support participants by minimizing the time and logistical demands of participation. This includes reducing site visits through the use of telehealth, mobile health professionals, and digital tools. The guidance also highlights the importance of reimbursing travel and other related costs, providing fair compensation for participants’ time, and offering multilingual materials and interpreter services when needed – all of which can significantly reduce barriers to participation.

4. Enhance recruitment and retention.

To improve recruitment and retention, trial teams should engage with the communities they serve.  Involving patients and advocacy groups early in trial planning can help sponsors better understand patient needs, priorities, and potential barriers to enrollment. When electing trial sites, sponsors should consider geographic areas with diverse populations and hire site staff who reflect those communities. The FDA also recomments leveraging real-world data, social media, and electronic informed consent to support outreach, while fostering trust through cultural compentency training and transparent communication.

5. Special considerations for rare diseases.

For rare disease trials, early collaboration with advocacy groups and clinical experts is essential. The guidance recommends considering re-enrollment from early-phase trials and open-label extension studies, as well as designing flexible protocols to maximize participation among small and geographically dispersed patient populations.

6. Expand access.

Despite efforts to broaden eligibility and reduce participation barriers, some patients may still be unable to enroll in clinical trials, particularly those with serious or immediately life-threatening conditions. In these cases, the FDA’s expanded access regulations provide a pathway for patients to potentially receive treatment with an investigational drug, provided specific criteria are met. Expanding access refers to the use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition, rather than to collect data typically obtained through clinical trials.

Widening eligibility and improving enrollment practices enhance trial quality, generate safety data that better reflects real-world populations, and support more equitable access to investigational therapies. We’re excited to see these FDA recommendations because they align with the types of trials EmVenio has been conducting since day one. This guidance further validates the work we’ve done, the studies we’re currently running, and the approach we’ll continue to take in the future.

If you’re ready to learn more about how our community-based research solutions help expand the reach of research to support better results for both patients and sponsors, contact us today!