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. 2025 Mar 27;145(13):1369-1381.
doi: 10.1182/blood.2023023717.

Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement

Uma Borate  1 , Kelly Pugh  1 , Allyson Waller  1 , Rina Li Welkie  1 , Ying Huang  1 , Jan Philipp Bewersdorf  2 , Maximilian Stahl  3 , Amy E DeZern  4 , Uwe Platzbecker  5 , Mikkael A Sekeres  6 , Andrew H Wei  7 , Rena J Buckstein  8 , Gail J Roboz  9 , Michael R Savona  10 , Sanam Loghavi  11 , Robert P Hasserjian  12 , Pierre Fenaux  13 , David A Sallman  14 , Christopher S Hourigan  15 , Matteo Giovanni Della Porta  16 , Stephen Nimer  6 , Richard F Little  17 , Valeria Santini  18 , Fabio Efficace  19 , Justin Taylor  6 , Guillermo Garcia-Manero  20 , Olatoyosi Odenike  21 , Tae Kon Kim  10 , Stephanie Halene  2 , Rami S Komrokji  14 , Elizabeth A Griffiths  22 , Peter L Greenberg  23 , Mina L Xu  24 , Zhuoer Xie  14 , Rafael Bejar  25 , Guillermo F Sanz  26   27   28 , Mrinal M Patnaik  29 , Maria Figueroa  6 , Hetty E Carraway  30 , Omar Abdel-Wahab  31 , Daniel Starczynowski  32 , Eric Padron  14 , Jacqueline Boultwood  33 , Steven Gore  17 , Naval G Daver  20 , Jane E Churpek  34 , Ravindra Majeti  23 , John M Bennett  35 , Alan F List  36 , Andrew M Brunner  37 , Amer M Zeidan  2
Affiliations

Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement

Uma Borate et al. Blood. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: A.M.Z. participated in advisory boards, and/or had a consultancy with, and received honoraria from, AbbVie, Pfizer, Celgene/Bristol Myers Squibb (BMS), Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, Otsuka, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Zentalis, Schrodinger, Regeneron, Syros, and Tyme and served on clinical trial committees for Novartis, AbbVie, Gilead, Syros, BioCryst, ALX Oncology, Kura, Geron, and Celgene/BMS. M.S. served on the advisory board for Novartis, Kymera, Sierra Oncology, GlaxoSmithKline, Rigel, BMS, Sobi, and Syndax; consulted for Boston Consulting, Gerson Lehrman Group, and Dedham group; and participated in continuing medical education activity for Novartis, Curis Oncology, Haymarket Media, and Clinical Care Options. A.E.D. participated in advisory boards, and/or had a consultancy with, and received honoraria from, Celgene/BMS, Agios, Novartis, Astellas, Gilead and served on clinical trial committees or data and safety monitoring boards for Novartis, AbbVie, Kura, Geron, Servier, Keros, and Celgene/BMS. U.P. reports research support and honoraria from BMS, Geron, Curis, AbbVie, and Janssen. D.A.S. reports research funding from Aprea Therapeutics and reports consulting for, and/or advisory board participation with, AbbVie, Agios, Akesobio, Avencell Europe GmbH, Bluebird Bio, BMS, Geron, Gilead Sciences, Janssen Global Services, Kite Pharma, Molecular Partners AG, Novartis, Servier Pharmaceuticals, Shattuck Labs, Syndax Pharmaceuticals, Syros Pharmaceuticals, and Takeda Pharmaceutical. F.E. reports consultancy or advisory role with AbbVie, Incyte, Novartis, and Jazz Pharmaceuticals and reports research support (institution) from Daiichi Sankyo, all outside the submitted work. E.A.G. declares honoraria for continuing medical education activity from Aplastic Anemia and MDS International Foundation, MedscapeLIVE, MediCom Worldwide, MJH Health, American Society of Hematology, MDS International Foundation, and Physicians Educational Resource; reports consulting fees from AbbVie, Alexion Pharmaceuticals, Apellis Pharmaceuticals, Takeda Oncology, Astex Pharmaceuticasls/Taiho Oncology, Alexion/AstraZeneca Rare Disease, Celgene/BMS, CTI BioPharma, Novartis, Partner Therapeutics, Picnic Health, and Servier; and reports research funding (to Roswell Park Comprehensive Cancer Center) from Alexion Pharmaceuticals, Apellis, Astex/Otsuka Pharmaceuticals/Taiho Oncology, Blueprint Medicines, Celldex Pharmaceuticals, Genentech, and NextCure Inc. M.L.X. served as consultant to Treeline Biosciences and Pure Marrow. A.W. served on the advisory board of Syndax Medical in October 2024, and served on the advisory board of Jazz Pharmaceuticals, Inc. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Schematic outlining the selection process of MDS trials. A total of 464 trials were selected for further screening after initial search results; 191 trials were included in the final analysis. Most trials incorporated MDS with AML.
Figure 2.
Figure 2.
Most common inclusion criteria in early-phase vs late-phase trials. There is a significant difference between early- and late-phase trials for inclusion criteria categorized as expected survival, bone marrow blasts, transfusion requirements, and washout periods.
Figure 3.
Figure 3.
Most common exclusion criteria in early-phase vs late-phase trials. There is a significant difference between early- and late-phase trials for exclusion criteria categorized as liver function tests, chronic viral illness, and prior treatments.
Figure 4.
Figure 4.
Overall concordance and discordance of eligibility criteria with drug safety signals. A safety signal (SS) is defined as the presence of a potential drug safety issue as identified by literature and pharmacist review. A limit is defined as eligibility criteria that is restrictive. The presence or absence of SS and limits for the following variables in each trial were assessed: EF, QTc limits, HIV, hepatitis B, hepatitis C, creatinine, ALT, AST, and total bilirubin. Stacked bars show concordance (shades of blue) and discordance (red and orange) between eligibility criteria and relevant drug safety signals. Numbers within the bars indicate the number of trials.
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References

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