Cleveland Clinic Cancer Researchers Find Eligibility Criteria In Clinical Trials Overly Strict

New research from Cleveland Clinic finds that clinical trials routinely use excessively strict enrollment criteria, which excludes patients who could potentially benefit from new treatments and limits trial results to a narrow group. The implications are that trials are not being designed to include participants who are representative of society, and therefore, safety results may not reflect what will be seen outside of strict trial eligibility criteria, or in some instances, what are reported on product labels.

The consequences of overly restrictive eligibility criteria may be categorized into two distinct levels: 1) the individual patient level, which emphasizes the negative impact of denying cancer patients access to cutting-edge therapies and 2) the societal level, which focuses on the limited generalizability of trial results.

“For patients, access to advanced therapies, especially for life-threatening diseases with undefined first-line treatment, is vital,” said Mikkael Sekeres, M.D., director of Cleveland Clinic leukemia program and co-author on the study. “However, fewer than five percent of adult cancer patients enroll in clinical trials, due in part to eligibility and screening failures.”

The study, in Leukemia, investigated the relationship between enrollment criteria and adverse events in 97 randomized controlled trials (RCTs) of blood cancers, such as leukemia, lymphoma, multiple myeloma and myelodysplastic syndromes, recently published in high impact journals.

Of the trials the team analyzed, 33 percent were conducted in leukemia, 28 percent in lymphoma, 34 percent in multiple myeloma, and 5 percent in myelodysplastic syndromes or myelofibrosis. Researchers found that specific, objective eligibility criteria for enrollment in RCTs routinely exclude patients with comorbidities and/or organ function abnormalities in a way that does not reflect the expected toxicities or observed adverse effects eventually seen in these patients. The alignment of renal, hepatic and/or cardiac toxicities and organ function exclusion criteria suggest eligibility criteria are overly conservative, introducing restrictions that may not be appropriate given the known toxicity of the treatment being studied.

“The goals of improving cancer trial conduct and efficiency are crucial if we are to advance cancer care rapidly,” adds Sekeres. “But without broadening access to studies for people with other medical conditions, the trials only rarely will be available to our cancer patients.”

The study results, coupled with evidence from post-hoc and long-term follow up analyses that suggests published safety data may be under-reported, indicate a need for modernized clinical trials with a more purposeful approach to eligibility criteria. Cleveland Clinic researchers believe the next step is to study adverse events and outcomes of patients who would have been excluded from trials but were actually treated on those trials.