Forty percent of Phase III cancer trials explicitly barred patients with an ECOG performance status of 2 or higher, and among trials that allowed those patients, they made up just 3.6% of enrolled participants. The FDA’s July 2026 final guidance on performance-status eligibility pushes directly against that pattern, recommending that adults with ECOG PS 2, or Karnofsky scores of 60 to 70, be included unless a specific scientific or clinical safety rationale justifies exclusion. For feasibility teams, the practical consequence is immediate: every assumption baked into a historical enrollment model was built under the old, narrower rules.
The problem is not simply that eligible headcounts will change. Historical enrollment records understate both the accessible population and the operational demands of supporting lower-functioning adults through a trial. A KRAS G12C eligibility analysis of 1,172 NSCLC patients at Columbia University Irving Medical Center illustrates why protocol criteria need study-specific scrutiny: eligibility rules shaped who reached trial enrollment in ways that aggregate registry data alone would not reveal. Teams that copy performance-status cutoffs from earlier protocols without re-examining the current safety evidence are building models on assumptions that the FDA now requires them to justify explicitly.
The guidance adds operational layers beyond the eligible headcount. The FDA recommends collecting baseline performance-status data, considering stratification when the enrolled range is broad, and supplementing clinician ratings with patient-reported functional assessments. Each of those requirements changes what a participating site must actually support: staffing for additional assessments, visit structures that accommodate patients with higher care needs, and escalation pathways for adverse-event patterns that narrower trials were never designed to detect. Feasibility questionnaires need to test those capacities directly, not assume that a site’s historical performance predicts its ability to run the proposed study.
The ASCO and Friends of Cancer Research joint work on eligibility criteria has long argued that restrictions should match scientific and safety objectives, not convention. The FDA’s final guidance gives that argument regulatory weight. The concrete marker to watch now is whether sponsors treat the guidance as a documentation exercise or as a genuine prompt to rerun scenarios with the broader criteria, conservative retention assumptions, and present-day site capacity confirmed rather than inferred.
Moe Alsumidaie, MBA, MSF, is founder and Chief Editor of Vanguard Publications, which publishes Clinical Trial Vanguard, Pharma Vanguard and BullScope, and Head of Research at CliniBiz. He has two decades in clinical trial operations and data science, with earlier roles at Genentech, Abbott Vascular and Stanford University Medical Center, and is a guest lecturer in clinical trial sciences at Rutgers University.
