Borate Uma, Pugh Kelly, Waller Allyson, Welkie Rina Li, Huang Ying, Bewersdorf Jan Philipp, Stahl Maximilian, DeZern Amy E, Platzbecker Uwe, Sekeres Mikkael A, Wei Andrew H, Buckstein Rena J, Roboz Gail J, Savona Michael R, Loghavi Sanam, Hasserjian Robert P, Fenaux Pierre, Sallman David A, Hourigan Christopher S, Della Porta Matteo Giovanni, Nimer Stephen, Little Richard F, Santini Valeria, Efficace Fabio, Taylor Justin, Garcia-Manero Guillermo, Odenike Olatoyosi, Kim Tae Kon, Halene Stephanie, Komrokji Rami S, Griffiths Elizabeth A, Greenberg Peter L, Xu Mina L, Xie Zhuoer, Bejar Rafael, Sanz Guillermo F, Patnaik Mrinal M, Figueroa Maria, Carraway Hetty E, Abdel-Wahab Omar, Starczynowski Daniel, Padron Eric, Boultwood Jacqueline, Gore Steven, Daver Naval G, Churpek Jane E, Majeti Ravindra, Bennett John M, List Alan F, Brunner Andrew M, Zeidan Amer M
Division of Hematology, The Ohio State University Comprehensive Cancer Center/James Cancer Hospital, The Ohio State University, Columbus, OH.
Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
Blood. 2025 Mar 27;145(13):1369-1381. doi: 10.1182/blood.2023023717.
Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly phase 3 trials, have unnecessarily restrictive eligibility criteria. This study aims to evaluate the most common eligibility criteria according to phase of trial and to determine whether criteria correspond with drug safety signals. We identified MDS clinical trials registered on ClinicalTrials.gov from 1 January 2000 to 1 September 2023 and analyzed the eligibility criteria of 191 therapeutic MDS trials. We found that categorical inclusion and exclusion criteria are remarkably similar in representation across trial phases. Additionally, only 13% of trials are concordant with drug safety signals, suggesting that the eligibility criteria are often arbitrary. On behalf of the icMDS (International Consortium for Myelodysplastic Syndromes), an association of international MDS experts, we provide a position statement on restrictive eligibility criteria for MDS clinical trials that should be avoided with the aim of removing barriers to clinical trial enrollment.
临床试验中过度严格的纳入和排除标准是骨髓增生异常综合征/肿瘤（MDS）患者参与临床试验的众多障碍之一。许多组织正在努力提高临床试验的入选资格；然而，最近几篇关注MDS患者的出版物表明，许多患有这种疾病的患者可能被不必要地排除在临床试验之外。临床试验的入选资格应反映研究阶段和所研究药物的风险。3期试验的限制应比早期试验少，以便尽可能贴近真实世界人群。我们假设许多临床试验，尤其是3期试验，具有不必要的严格入选标准。本研究旨在根据试验阶段评估最常见的入选标准，并确定这些标准是否与药物安全信号相符。我们确定了2000年1月1日至2023年9月1日在ClinicalTrials.gov上注册的MDS临床试验，并分析了191项MDS治疗性试验的入选标准。我们发现，不同试验阶段的分类纳入和排除标准在表述上非常相似。此外，只有13%的试验与药物安全信号一致，这表明入选标准往往是随意的。代表国际MDS专家协会icMDS（国际骨髓增生异常综合征联盟），我们就MDS临床试验中应避免的严格入选标准发表立场声明，旨在消除临床试验入组的障碍。
