Eligibility criteria in pediatric oncology phase I and II clinical trials: Analysis and recommendations for standardization from the Innovative Therapies for Children and Adolescents with Cancer (ITCC) Consortium

Introduction Eligibility criteria safeguard trial integrity and safety, yet restrictive requirements frequently limit patient access and generalizability. While initiatives exist to simplify criteria in adult populations, evidence supporting their use and justification within pediatric oncology remains undefined. Methods Sixty-four protocols from 48 ITCC phase I–II trials (2011–2020) were evaluated. Protocol, literature analysis, and regulatory standards review was performed. Eligibility criteria were quantified and categorized by frequency: High (appeared in '66% of protocols), average (33%–66%), and low ('33%). For each high-frequency and relevant criteria identified in the literature review, the scientific justification provided within the trial protocol was assessed. Results Analysis revealed a median of 28 criteria per protocol (range 12–49), with a significant increase between 2011–2016 and 2017–2020 (p = 0.05). Substantial heterogeneity was observed in organ function thresholds and washout periods, irrespective of investigational agent characteristics. Repetition was prevalent; 69% of trials repeated similar criteria in both inclusion and exclusion sections. Notably, a median of only 7% (range 0%–62%) of high-frequency and relevant criteria possessed scientific justification within the protocol, with several exclusion categories lacking justification entirely. Conclusion Pediatric early-phase trial eligibility criteria are increasingly complex, heterogeneous and predominantly lacking justification. We recommend implementing evidence-based, medically relevant requirements to optimize patient accrual and representation. Harmonizing these standards is essential to maintain safety while ensuring broader access to innovative therapies in pediatric drug development.