USFDA Guidance: Cancer Clinical Trial Eligibility Criteria – Laboratory Values, Washout Periods and Concomitant Medications, and Performance Status
- Sharan Murugan
- 5 minutes ago
- 3 min read
Appropriate eligibility criteria are essential for protecting trial participants while ensuring that clinical trial populations are representative of patients who are expected to receive the investigational therapy in clinical practice. Overly restrictive eligibility criteria may unnecessarily exclude patients, delay trial enrollment, and limit the applicability of study results.
The three FDA guidances—Cancer Clinical Trial Eligibility Criteria: Laboratory Values, Cancer Clinical Trial Eligibility Criteria: Washout Periods and Concomitant Medications, and Cancer Clinical Trial Eligibility Criteria: Performance Status—provide recommendations for designing scientifically justified eligibility criteria that improve trial inclusiveness while maintaining patient safety.
This guidance provides recommendations for selecting laboratory value-based eligibility criteria that are scientifically justified and appropriate for the investigational drug and study population. Laboratory criteria should protect patient safety without unnecessarily excluding participants who may safely benefit from clinical trial participation.
Scientific Justification for Laboratory Values
Laboratory-based eligibility criteria should be developed based on the investigational drug's mechanism of action, pharmacokinetic and pharmacodynamic characteristics, anticipated toxicities, and available clinical data. Criteria should be tailored to the specific investigational product rather than being carried forward from previous studies without scientific justification.
Restrictions related to renal, hepatic, or hematologic function should only be applied when supported by evidence demonstrating a meaningful safety concern.
Accounting for Expected Laboratory Variations
When establishing laboratory eligibility criteria, sponsors should consider the characteristics of the target patient population and recognize that laboratory values may naturally vary because of disease, age, race, ethnicity, or other clinical factors. Broadening laboratory ranges where appropriate may improve trial enrollment while generating data that better reflect the intended treatment population.
The guidance also recommends considering repeat laboratory testing when isolated abnormal values may not be clinically significant.
Routine Reassessment of Eligibility Criteria
Laboratory-based exclusion criteria should be routinely reassessed throughout drug development. As additional pharmacology, safety, and clinical data become available, sponsors should revise eligibility criteria by removing or relaxing restrictions that are no longer scientifically justified, particularly during later-phase clinical trials.
This guidance provides recommendations for establishing washout periods and concomitant medication restrictions based on scientific evidence rather than routine practice. Eligibility criteria should support participant safety while avoiding unnecessary barriers to clinical trial enrollment.
Washout Periods
Washout periods should be determined according to the characteristics of previous therapies and the investigational product rather than relying solely on fixed time intervals. Relevant clinical and laboratory parameters may be more appropriate than predefined time-based requirements when determining patient eligibility.
Where time-based washout periods are necessary, they should be supported by scientific justification, including pharmacokinetic and pharmacodynamic considerations, and clearly described within the study protocol.
Concomitant Medications
Patients should only be excluded because of concomitant medications when clinically relevant drug-drug interactions or overlapping toxicities are expected to affect patient safety.
Rather than excluding patients, sponsors may consider modifying the dosage or treatment regimen of the investigational product or concomitant medications where appropriate. Any such modifications should be clearly described within the study protocol, and participants should receive adequate information regarding these changes.
This guidance provides recommendations for broadening performance status eligibility criteria while maintaining appropriate patient protection. The recommendations are intended to improve the representativeness of oncology clinical trials and better characterize the benefit-risk profile of investigational therapies.
Considerations for Including Patients with Lower Performance Status
Performance status is commonly used as an eligibility criterion because it reflects a patient's ability to perform daily activities. However, excluding patients with lower performance status may reduce trial enrollment and limit the generalizability of study findings.
The guidance discusses both the potential advantages of broader inclusion, including improved enrollment and greater applicability of trial results, and potential challenges such as increased adverse events, retention considerations, and possible effects on study outcomes.
Recommendations for Performance Status Eligibility
Patients with lower performance status should be included whenever there is no scientific or clinical justification for exclusion. Eligibility criteria should reflect the population expected to receive the investigational treatment in clinical practice and should be updated throughout drug development as additional safety and efficacy data become available.
Performance status information should be collected consistently, and where appropriate, incorporated as a stratification factor during trial design.
Additional Functional Assessments
The guidance recommends complementing traditional performance status scales with additional assessments that provide a more comprehensive understanding of patient functional status. Patient-reported outcomes, digital health technologies, and assessments of overall health status may provide valuable information without unnecessarily limiting trial participation.