Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement Journal Article


Authors: Kim, E. S.; Bruinooge, S. S.; Roberts, S.; Ison, G.; Lin, N. U.; Gore, L.; Uldrick, T. S.; Lichtman, S. M.; Roach, N.; Beaver, J. A.; Sridhara, R.; Hesketh, P. J.; Denicoff, A. M.; Garrett-Mayer, E.; Rubin, E.; Multani, P.; Prowell, T. M.; Schenkel, C.; Kozak, M.; Allen, J.; Sigal, E.; Schilsky, R. L.
Article Title: Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement
Abstract: Purpose The primary purposes of eligibility criteria are to protect the safety of trial participants and define the trial population. Excessive or overly restrictive eligibility criteria can slow trial accrual, jeopardize the generalizability of results, and limit understanding of the intervention's benefit-risk profile. Methods ASCO, Friends of Cancer Research, and the US Food and Drug Administration examined specific eligibility criteria (ie, brain metastases, minimum age, HIV infection, and organ dysfunction and prior and concurrent malignancies) to determine whether to modify definitions to extend trials to a broader population. Working groups developed consensus recommendations based on review of evidence, consideration of the patient population, and consultation with the research community. Results Patients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale. In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients older than age 12 years. HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion. Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves renal excretion. Patients with prior or concurrent malignancies should be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low. Conclusion To maximize generalizability of results, trial enrollment criteria should strive for inclusiveness. Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation. © 2017 by American Society of Clinical Oncology.
Keywords: liver function; patient selection; clinical trials as topic; liver dysfunction; united states; human immunodeficiency virus infection; organization and management; consensus; biomedical research; heart disease; oncology; age; alanine aminotransferase blood level; aspartate aminotransferase blood level; alanine aminotransferase; aspartate aminotransferase; bilirubin; kidney function; medical research; patient safety; brain metastasis; medical society; medical oncology; bilirubin blood level; early detection of cancer; creatinine clearance; clinical trial (topic); human immunodeficiency virus infected patient; kidney dysfunction; eligibility determination; urinary excretion; electrocardiography monitoring; procedures; experimental therapy; low risk population; humans; human; priority journal; article; new york heart association class; early cancer diagnosis
Journal Title: Journal of Clinical Oncology
Volume: 35
Issue: 33
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2017-11-20
Start Page: 3737
End Page: 3744
Language: English
DOI: 10.1200/jco.2017.73.7916
PUBMED: 28968170
PROVIDER: scopus
PMCID: PMC5692724
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Stuart Lichtman
    163 Lichtman