Strict clinical trial eligibility criteria exclude patients most likely to benefit from cancer treatment

Clinical trials routinely use strict enrollment criteria that exclude patients who are most likely to benefit from the treatment under investigation, according to study results published in Leukemia.

Trials are not being designed to include participants who are representative of society, Mikkael A. Sekeres, MD, MS, director of the leukemia program in the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute, and colleagues concluded.

Mikkael A. Sekeres

Consequently, trial results may not reflect what will occur outside of a clinical trial.

“For patients, access to advanced therapies — especially for life-threatening diseases with undefined first-line treatment — is vital,” Sekeres said in a press release. “However, fewer than 5% of adult [patients with cancer] enroll in clinical trials, due in part to eligibility and screening failures.”

HemOnc Today spoke with Sekeres about the study results, their potential implications, and how members of the clinical community can help drive change in this area.

Question: Can you describe the study and the key findings?

Answer: Abby Statler, MPH, MA, research regulatory quality assurance coordinator at Taussig Cancer Institute, served as lead author and initiated this study. In reviewing studies, she observed many similarities in the eligibility criteria of cancer trials. We decided to formally study this and see whether eligibility criteria were actually sensitive to known drug toxicities, or if they represented a ‘cut-and-paste’ job. We decided to focus on hematologic malignancies as a starting point. We searched journals with a high impact factor. We identified 97 studies, of which one-third were conducted in leukemia, 28% in lymphoma, 34% in multiple myeloma and 5% in myelodysplastic syndrome. We first assessed known toxicities of the drugs studied in each trial to see whether they aligned with eligibility criteria. For example, a study may say a patient is not eligible to participate if their creatinine is 1.5 times the upper limit of normal, or if their liver function is 2.5 times the upper limit of normal. We found that the known toxicities of these drugs did not correlate with the cardio-hepatic or renal eligibility criteria of the trials. Eligibility criteria were not sensitive to what was known about those drugs in terms of their toxicities. We then looked to see whether patients actually had the toxicities for which they may have been excluded. Once again, we found that for hepatic and renal eligibility criteria, they did not correlate with observed adverse events on those studies.