The FDA's Oncology Center of Excellence (OCE) has issued 3 final guidance documents intended to broaden eligibility criteria for participation in clinical trials evaluating oncology drugs, with the documents addressing performance status, washout periods and concomitant medications, and laboratory values.1-4
According to the FDA, fewer than 5% of patients with cancer who are currently receiving treatment are enrolled in clinical trials, despite more than 70% reporting that they are willing to participate.1 The guidance documents aim to target stringent and complex eligibility criteria that could impede enrollment, and each document addresses a distinct area in which rigid requirements limit enrollment.
“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 in a news release.
The final documents follow draft versions the OCE issued in April 2024 and are part of a series developed through workshops with Friends of Cancer Research and ASCO.
What problems do the guidance documents address?
Eligibility criteria that are more restrictive than necessary have long been cited as a barrier to trial accrual and to the generalizability of trial findings. When enrolled populations diverge substantially from the patients who will ultimately receive an approved drug, the resulting efficacy and safety data may not fully reflect real-world use. By encouraging sponsors, institutional review boards (IRBs), and clinical investigators to reconsider criteria that exclude patients without a clear scientific or safety rationale, the guidances are intended to widen the pool of eligible participants and produce data more representative of clinical practice.
Each of the three final guidance documents focuses on a specific category of criteria in which the OCE has identified opportunities to expand eligibility.
How does each guidance modify eligibility criteria?
The final guidance on performance status addresses the use of performance status which is a common measure of how well a patient can perform ordinary tasks and carry out activities of daily living.2 The guidance raises questions about applying performance status as a rigid eligibility criteria, noting that some patients may have a low performance status since cancer has made them sick, which could improve once the they are enrolled and receiving treatment. Overly strict performance-status cutoffs can therefore exclude patients who might benefit from and safely tolerate an investigational agent.
FDA Trial Eligibility Criteria Guidance: Key Points
- The performance status guidance questions reliance on performance status as a rigid cutoff, noting that a low score driven by cancer may improve after a patient begins treatment.
- The washout and concomitant medications guidance asks sponsors to justify whether time-based washout periods are necessary and makes allowances for patients taking other medications.
- The laboratory values guidance calls for a more scientific, safety-focused approach to the test thresholds used to determine eligibility.
Furthermore, the FDA also outlined recommendations for alternative trial designs, which could comprise prespecified cohorts for patients with a lower performance status. Assessments of functional status given during a study could also help better characterize the functional status of patients at baseline and during the course of treatment.
The final guidance on washout periods and concomitant medications encourages sponsors to evaluate whether time-based washout periods are necessary for a given study.3 The document also makes some allowances for patients who are taking other medications, an accommodation intended to avoid excluding patients whose comorbidities require ongoing treatment.
The laboratory values final guidance overviews a more scientific and safety-based approach to the laboratory tests commonly used to determine whether a patient qualifies for a study.4 Rather than defaulting to conventional thresholds, 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, an approach designed to avoid unjustified exclusions.
Additionally, the FDA outlined that eligibility criteria regarding laboratory values should be adjusted based on clinical experience. For example, first-in-human studies of first-in-class drugs or platforms should include convention eligibility criteria as a precautionary measure before subsequent studies of drugs or platforms within the same class can have adjusted criteria based on prior experience.
References
- Final guidances to expand participation in cancer clinical trials. FDA Oncology Center of Excellence. July 2026. Accessed July 27, 2026. https://www.fda.gov/about-fda/oncology-center-excellence/oncology-center-excellence-guidance-documents
- Cancer clinical trial eligibility criteria: performance status. FDA. July 27, 2026. Accessed July 27, 2026. https://www.fda.gov/media/178018/download
- Cancer clinical trial eligibility criteria: washout periods and concomitant medications. FDA. July 27, 2026. Accessed July 27, 2026. https://www.fda.gov/media/178016/download
- Cancer clinical trial eligibility criteria: laboratory values. FDA. July 27, 2026. Accessed July 27, 2026. https://www.fda.gov/media/178013/download
