FDA narrows cancer trial rules

The U.S. Food and Drug Administration published final guidance on July 28 telling cancer-trial sponsors, investigators and institutional review boards to justify key eligibility rules with evidence rather than carry forward standard cutoffs by habit. The agency finalized documents on laboratory values and performance status, and pointed to separate recommendations on washout periods and concomitant medications. FDA said the aim is to avoid unjustified exclusions while still selecting the intended study population and reducing risks to trial participants. ### Which trial rules is the FDA targeting? The July 28 Federal Register notices said the new final guidances cover laboratory values and performance status in cancer trials. FDA said the laboratory-values document recommends selecting appropriate lab thresholds “to avoid unjustified exclusions of trial participants,” while the performance-status document recommends expanding eligibility to include patients with a wider range of performance status. (federalregister.gov) The FDA page for washout periods and concomitant medications says that guidance addresses the “appropriate use of washout periods and concomitant medication exclusions.” That document remains listed as draft guidance dated April 2024, but it is part of the same broader eligibility-criteria series described by the agency. (federalregister.gov) ### What does the laboratory-values guidance tell sponsors to do differently? The July 2026 laboratory-values guidance says eligibility criteria are used to select the intended patient population and reduce potential risks, but it also includes sections on “Scientific Justification for Laboratory Tests as Exclusion Criteria,” “Accounting for Potential Expected Variations in Laboratory Values,” and “Routine Reassessment of Laboratory-Based Exclusion Criteria.” The document says it reflects the FDA’s current thinking and is not binding. (fda.gov) The Federal Register notice for that guidance says sponsors should use laboratory values as eligibility criteria in a way that avoids unjustified exclusions. Read together, the notice and the guidance show the agency is pressing sponsors to explain why a given lab cutoff is needed for safety or trial design, rather than adopting thresholds from earlier protocols without a documented basis. (fda.gov) ### Why is performance status part of the same push? The July 28 performance-status notice said the final guidance recommends expanding eligibility criteria to include patients with a wider range of performance status. FDA’s notice said the document finalizes a draft issued on April 26, 2024. (federalregister.gov) The ASCO Post, summarizing the three guidance documents, said performance status can be affected by cancer itself and may improve after a patient starts treatment in a trial. That is one reason the agency is revisiting rigid entry rules that can keep patients out before investigators assess whether participation is appropriate. (federalregister.gov) ### How broad is the participation problem the FDA is responding to? The ASCO Post said fewer than 5% of cancer patients currently receiving treatment are enrolled in clinical trials, even though more than 70% say they are willing to participate. The publication said the guidances address one contributor to that gap: stringent and complex eligibility criteria. (ascopost.com) The same ASCO Post report quoted the guidances’ preambles as saying “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 eventual treatment population. That rationale links enrollment and representativeness to the agency’s narrower focus on lab thresholds, performance measures and medication-related exclusions. (ascopost.com) ### Where do washout periods fit into this? The FDA’s washout-periods draft guidance says eligibility criteria are sometimes more restrictive than necessary and that broader eligibility may improve the diversity of trial populations. It specifically addresses whether time-based washout periods are appropriate and how sponsors should think about exclusions tied to concomitant medications. (ascopost.com) The ASCO Post said that document encourages sponsors to consider whether a time-based washout is necessary between stopping one cancer drug and starting an investigational treatment. That places washout periods in the same category as lab cutoffs and performance-status limits: rules the FDA wants tied to a scientific or safety rationale. (fda.gov) ### What happens next for sponsors and investigators? The FDA said comments on agency guidances may be submitted at any time through Regulations.gov, and the July 28 notices identify dockets FDA-2024-D-1402 for laboratory values and FDA-2024-D-1377 for performance status. Sponsors designing oncology studies can now use the final July 2026 guidances, while the washout-periods document remains a draft dated April 2024 on the agency’s website. (ascopost.com) (federalregister.gov)