Clinical trials are essential for developing new medicines. But for research to reflect how treatments work in the real world, the participants in those trials should resemble the patients who will ultimately use the therapies.
At TrialX, we work with sponsors and research teams to support more inclusive clinical trials—and the latest FDA guidance aligns closely with what we see as the future of patient-centered research. In December 2025, the U.S. Food and Drug Administration released guidance outlining practical steps sponsors can take to improve participation in clinical trials for new drugs and biologics. The guidance emphasizes a central goal: ensuring that clinical trial populations better reflect the diversity of patients seen in clinical practice—including differences in age, sex, race, health conditions, and other real-world factors.
As the FDA notes in the document:
“Broadening eligibility criteria and improving enrollment practices can help ensure that clinical trials include populations that are representative of the patients likely to use the drug in clinical practice.”
To support this goal, the agency highlights three areas where sponsors can make meaningful improvements: eligibility criteria, trial design, and participation practices.
1. Rethinking Eligibility Criteria
Eligibility criteria play an important role in clinical research. They help protect participants and ensure that studies generate scientifically reliable results. However, the FDA notes that some criteria become overly restrictive over time, particularly when they are reused across studies without careful reassessment. In the early stages of drug development, certain exclusions may be necessary. For example:
- Patients with severe kidney or liver impairment may initially be excluded until researchers better understand how the drug is metabolized.
- Pregnant or breastfeeding women may be excluded when potential risks to the fetus or infant are unknown.
As more safety data becomes available, the FDA encourages sponsors to re-evaluate these exclusions. Sponsors are encouraged to examine whether each eligibility criterion remains necessary for participant safety or study objectives. If not, it may be possible to modify or remove the restriction.
The agency also recommends reviewing eligibility criteria used in Phase 2 trials, which are often carried forward into Phase 3 studies without modification. Since later-stage trials are intended to evaluate treatments in broader patient populations, reassessing these criteria can help ensure the study population better reflects real-world patients.
Ensuring representation across key populations is equally important. Sponsors should aim to include participants across:
- Age groups, including older adults
- Women and men in sufficient numbers to analyze potential differences in response
- Racial and ethnic populations that may be underrepresented in research
- Patients with complex health conditions or disabilities
Collecting data across diverse populations helps researchers better understand how treatments perform in different groups and identify potential differences in safety or effectiveness.
2. Using Trial Design Strategies to Support Inclusion
In addition to eligibility criteria, the way a study is designed can significantly influence who is able to participate.
The FDA encourages sponsors to consider trial design strategies that allow broader participation while maintaining scientific rigor and reliable study outcomes. Planning for representative enrollment early during protocol development can help ensure that clinical trials include populations likely to use the therapy once it is approved.
One approach involves the use of enrichment strategies, which select participants who are more likely to demonstrate a treatment effect. These strategies can improve trial efficiency while still allowing researchers to study therapies in relevant patient populations.
Enrichment approaches typically fall into two categories:
- Prognostic enrichment, which enrolls participants more likely to experience the clinical endpoint being studied
- Predictive enrichment, which selects participants based on biological characteristics—such as biomarkers or genetic markers—that suggest they may respond to a treatment
3. Reducing Barriers to Participation
Even when patients meet eligibility requirements, practical challenges can prevent them from enrolling in or remaining in a clinical trial.
Common barriers include:
- Frequent travel to research sites
- Time away from work or caregiving responsibilities
- Transportation or lodging costs
- Limited awareness of clinical trial opportunities
- Language barriers
To address these issues, the FDA recommends designing trials in ways that reduce participation burden wherever possible.
These strategies may include:
- Decentralized or hybrid trial models that allow certain study activities to take place outside traditional research sites
- Telehealth visits and remote data collection tools that reduce the need for frequent in-person appointments
- Home visits by trained healthcare professionals, such as nurses or phlebotomists, for procedures like sample collection
- Reimbursement for reasonable participant expenses, including travel, lodging, or meals when reviewed by institutional review boards
- Partnerships with patient advocacy groups and community organizations to improve awareness of clinical trial opportunities
- Multilingual study materials and interpretation services to ensure patients can understand study information and provide informed consent
Reducing logistical and communication barriers can make it easier for a wider range of patients to participate in clinical research.
Special Considerations for Rare Disease Trials
Rare disease trials often face additional challenges because eligible patients may be small in number and geographically dispersed.
To address this, the FDA suggests several approaches, including:
- Engaging patient advocacy groups early in the development process
- Considering re-enrollment of participants from earlier trial phases when appropriate
- Offering open-label extension studies so participants can access investigational therapies after initial trial phases
These strategies can help researchers collect meaningful safety and effectiveness data from the limited patient populations available.
What This Means for Sponsors
The FDA guidance reflects a broader shift toward more inclusive and patient-centered clinical research.
For sponsors, this means clinical trials must increasingly be designed with real-world patient populations in mind—from eligibility criteria and site selection to recruitment and operational strategies.
Improving participation in clinical trials can lead to:
- More comprehensive safety data
- Better understanding of treatment effects across diverse populations
- Stronger evidence to support regulatory decisions and product labeling
Supporting More Inclusive Clinical Trials
The FDA guidance highlights several approaches that can help improve participation in clinical trials, including broader patient outreach, reducing logistical barriers, and enabling more flexible participation models.
At TrialX, our patient recruitment and remote research data collection platforms are designed to support these efforts by helping research teams connect with patients and facilitate participation in both traditional and decentralized clinical trials.
We support clinical trial participation through several capabilities:
AI-powered trial matching
TrialX’s AI-powered clinical trial finder uses natural language processing and machine learning to match patient profiles with relevant trials. By analyzing structured eligibility criteria and patient-provided information such as condition and location, the platform identifies studies that may be a good fit and presents personalized trial options.
AI-powered trial navigator
TrialX’s AI navigator—an interactive avatar—helps guide patients through the trial discovery process and prescreens them to identify studies that match their health conditions and preferences.
Simplified trial information
Clinical trial descriptions often contain complex medical terminology. TrialX uses AI-based tools to translate technical trial information into clearer, patient-friendly summaries, helping potential participants better understand study requirements.
Multilingual trial discovery
TrialX supports trial discovery across 18 countries and 22 languages, with plans to expand to 40 countries soon. Multilingual trial listings, prescreeners, and recruitment materials help ensure that patients can explore research opportunities in languages they are comfortable using.
Support for decentralized and hybrid trials
Our digital engagement tools support decentralized and hybrid trial models by enabling remote communication, prescreening, and participant engagement, helping reduce the need for frequent site visits.
