Increasing Complexity of Clinical Trial Criteria in AML and MDS: Impact on Patient Eligibility and Generalizability

Over the past decade, clinical trials in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have become increasingly complex, with expanding inclusion and exclusion criteria, longer trial durations, and evolving primary and secondary endpoints. While these changes aim to refine trial design and ensure patient safety, they may inadvertently narrow eligibility, limiting external validity and reducing the generalizability of trial outcomes to real-world populations. This study systematically evaluates the trajectory of AML and MDS clinical trial design over the past five years, with a primary focus on the complexity of eligibility criteria. We compiled and analyzed trial protocols to characterize temporal trends in inclusion and exclusion parameters, trial duration, and endpoint selection. To assess real-world applicability, we applied these criteria to patient cohorts at Yale Cancer Center, quantifying the proportion of patients who would have been eligible for participation. By integrating trial-level and patient-level analyses, this study highlights the widening gap between clinical trial populations and patients seen in everyday practice. Our findings aim to inform future trial design, balance rigor with inclusivity, and enhance the translational value of AML and MDS research by ensuring outcomes are more broadly representative of the populations most affected by these diseases.