FDA Finalizes Three Guidances to Broaden Cancer Clinical Trial Eligibility

The FDA's Oncology Center of Excellence (OCE) has issued three final guidance documents intended to expand eligibility criteria for participation in oncology clinical trials, targeting a persistent and well-documented gap in cancer research participation.¹

According to the FDA, despite more than 70% of cancer patients reporting willingness to participate in clinical trials, fewer than 5% of those currently receiving treatment are actually enrolled.

The guidances identify stringent and complex eligibility criteria as a key contributor to that gap.

"Unnecessarily restrictive eligibility criteria may slow subject accrual, limit patients' access to clinical trials, and lead to trial results that do not fully represent treatment effects in the patient population that will ultimately use the drug," the FDA wrote across all three documents.

The final documents follow draft versions issued by the OCE in April 2024 and are part of a series developed through workshops with Friends of Cancer Research and ASCO. They also advance one of the goals of the US Department of Health and Human Services’ Operation TrialBlazer Initiative, which tasked the FDA with improving patient and participant access and engagement in clinical trials.

Performance status

The first guidance addresses the use of performance status—a common measure of how well a patient can perform ordinary tasks and daily activities—as a rigid eligibility criterion.²

The guidance raises concerns about applying strict performance status cutoffs, noting that some patients may have a low score because cancer has made them sick, a condition that could improve once the patient begins receiving treatment. Excluding these patients on the basis of a low score at baseline may therefore eliminate individuals who could safely tolerate and benefit from an investigational agent.

The FDA also outlined recommendations for alternative trial designs, including prespecified cohorts for patients with lower performance status, and suggested that functional status assessments conducted during a study could better characterize patients' baseline and in-treatment functional capacity.

Washout periods and concomitant medications

The second guidance addresses washout periods—the time between stopping one cancer drug and beginning an experimental one—and the treatment of patients taking other medications.

The document encourages sponsors to evaluate whether time-based washout periods are scientifically necessary for a given study, rather than applying them by default, and makes allowances for patients whose comorbidities require ongoing medication, an accommodation intended to avoid unjustified exclusions.

Laboratory values

The third guidance calls for a more scientific and safety-focused approach to the laboratory test thresholds commonly used to determine trial eligibility. Rather than defaulting to conventional cutoffs, the guidance directs sponsors toward laboratory-value criteria grounded in the safety profile of the investigational drug and the biology of the disease under study.

The FDA also noted that eligibility criteria around laboratory values should be adjusted based on clinical experience. For example, first-in-human studies of first-in-class drugs or platforms should include conventional eligibility criteria as a precautionary measure, while subsequent studies of drugs within the same class can have criteria adjusted based on prior experience.

Broader context

When enrolled trial populations diverge substantially from the patients who will ultimately receive an approved drug, the efficacy and safety data generated may not fully reflect real-world use. By encouraging sponsors, IRBs, and clinical investigators to reconsider criteria that exclude patients without a clear scientific or safety rationale, the guidances are intended to both widen the pool of eligible participants and produce data more representative of clinical practice.

The three documents are part of a broader series the OCE has been developing in collaboration with ASCO and Friends of Cancer Research, and reflect continued regulatory momentum toward making oncology trials more inclusive and operationally accessible.

References

1. FDA Releases Final Guidances to Expand Participation in Cancer Clinical Trials. The ASCO Post. July 28, 2026. Accessed July 29, 2026. https://ascopost.com/news/july-2026/fda-releases-final-guidances-to-expand-participation-in-cancer-clinical-trials/
2. Oncology Center of Excellence Guidance Documents. FDA. July 27, 2026. Accessed July 29, 2026. https://www.fda.gov/about-fda/oncology-center-excellence/oncology-center-excellence-guidance-documents