Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement
Abstract
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.
Article Details
Authors (51)
Uma Borate
2Ohio State University Comprehensive Cancer Center, Columbus, United States
Kelly Pugh
2The Ohio State University Comprehensive Cancer Center/James Cancer Hospital, The Ohio State University, Division of Hematology, Columbus, United States
Allyson Waller
1The James Cancer Hospital and Solove Research Institute at The Ohio State University, Department of Pharmacy, Columbus, United States
Rina Li Welkie
Ying Huang
Jan Philipp Bewersdorf
Maximilian Stahl
Amy E. DeZern
4Division of Hematology Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD
Uwe Platzbecker
Mikkael A. Sekeres
14University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL
Andrew H. Wei
Rena J. Buckstein
8Department of Medical Oncology/Hematology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Gail J. Roboz
Weill Cornell Medicine, New York Presbyterian Hospital, New York
Michael R. Savona
Department of Internal Medicine, Vanderbilt University School of Medicine
Sanam Loghavi
Robert P. Hasserjian
Massachusetts General Hospital
Pierre Fenaux
David A. Sallman
6Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
Christopher S. Hourigan
1Fralin Biomedical Research Institute, Virginia Tech Fralin Biomedical Research Institute Cancer Research Center, Washington, DC
Matteo Giovanni Della Porta
Stephen Nimer
6Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Division of Hematology, Miami, United States
Richard F. Little
17National Cancer Institute, Cancer Therapy Evaluation Program, Rockville, MD
Valeria Santini
7DMSC University of Florence, AOUC, MDS Unit, Hematology, Florence, Italy
Fabio Efficace
1Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
Justin Taylor
Guillermo Garcia-Manero
Olatoyosi Odenike
University of Chicago Medicine and Comprehensive Cancer Center, Chicago
Tae Kon Kim
1Vanderbilt University Medical Center, Division of Hematology/Oncology, Department of Medicine, Nashville, United States
Stephanie Halene
Department of Pathology, Yale School of Medicine
Rami S. Komrokji
H. Lee Moffitt Cancer Center, Tampa, Florida, United States
Elizabeth A. Griffiths
Roswell Park Comprehensive Cancer Center, Buffalo, NY
Peter L. Greenberg
1Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
Mina L. Xu
Zhuoer Xie
Moffitt Cancer Center, Tampa, Florida, United States
Rafael Bejar
Guillermo F. Sanz
26Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Mrinal M. Patnaik
Division of Hematology, Department of Internal Medicine, Mayo Clinic
Maria Figueroa
6Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
Hetty E. Carraway
30Division of Hematologic Oncology and Blood Disorders, Leukemia Program, Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
Omar Abdel-Wahab
Molecular Pharmacology Program, Sloan Kettering Institute
Daniel Starczynowski
3Cincinnati Children's Hospital Medical Center, Division of Experimental Hematology, Cincinnati, United States
Eric Padron
Moffitt Cancer Cancer and Research Institute, Tampa, Florida, United States
Jacqueline Boultwood
Steven Gore
Naval G. Daver
Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas USA
Jane E. Churpek
Ravindra Majeti
2Stanford University
John M. Bennett
Department of Chemistry, Stanford University
Alan F. List
36Precision BioSciences, Inc, Durham, NC
Andrew M. Brunner
37Division of Hematology and Oncology, Leukemia Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Amer M. Zeidan