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Evolution of eligibility criteria for non-transplant randomized controlled trials in adults with acute myeloid leukemia


Eligibility criteria for clinical trials are intended to select suitable study subjects but can limit trial participation and generalization of results. While reported for other cancers, non-enrollment rates and evolution of eligibility criteria over time have so far not been studied for randomized controlled trials (RCTs) involving adults with acute myeloid leukemia (AML). Among 3698 studies published between 2010 and 2020, including 447 involving prospective clinical trials, we identified 75 phase three RCTs testing non-transplant therapies for adults with AML. Only 31 studies (41%) provided information on non-enrollment; in these studies, the median non-enrollment rate was 23%, primarily attributed to restrictive eligibility criteria. In 95% of trials, eligibility criteria were reported with the total number per trial increasing over time (P < 0.001), particularly in industry-funded trials. A total of 27 eligibility criteria were used across trials, mostly concerning comorbidities or performance status, with eight of them becoming more common over time. The concordance with recent ASCO – Friends of Cancer Research eligibility criteria recommendations greatly varied, from 35% to 99%. Together, our analyses suggest that the ability to generalize results from non-transplant RCTs may be increasingly limited because of high non-enrollment rates and increasingly restrictive eligibility criteria.

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Fig. 1: Evolution of number of total eligibility criteria required overtime.
Fig. 2: Number of eligibility criteria according to the type of drug studied and according to industry funding.
Fig. 3: Change in the requirement for each individual eligibility criteria over time.
Fig. 4: Observance of ASCO-Friends of Cancer Research recommendations.


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The study was originally conceived and designed with Professor Elihu H. Estey who passed away before it could be completed. We are thankful for his mentorship on this work and so many others.

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Authors and Affiliations



Conception and Design: CO, RBW. Collection and Assembly of Data: CO, GJ. Data Analysis and Interpretation: CO, MO, MHB, FRA, RBW. Manuscript Writing: All authors. Final Approval of the Manuscript: All authors.

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Correspondence to Roland B. Walter.

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Employment or Leadership Position: none; Consultant or Advisory Role: MHB, Erytech©; Stock Ownership: none; Honoraria: CO, Novartis, MHB, Abbvie, Incyte, and Jazz Pharmaceuticals; Research Funding: none; Expert Testimony: none; Patents: none; Other Remuneration: none.

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Orvain, C., Othus, M., Johal, G. et al. Evolution of eligibility criteria for non-transplant randomized controlled trials in adults with acute myeloid leukemia. Leukemia (2022).

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