Clinical trials routinely use overly strict enrollment criteria, found a recent study.1 “Real-world patients are often excluded from clinical trials because they do not meet the restrictive eligibility criteria,” says lead author Abby Statler, MPH, MA, research regulatory quality assurance coordinator for the leukemia program in the Department of Hematology and Medical Oncology at Cleveland (OH) Clinic.

Researchers studied the relationship between eligibility criteria and adverse events in randomized controlled trials of hematologic malignancies. “We wanted to understand if there are specific criteria that may be responsible for inappropriately excluding patients,” Statler explains.

The results suggest that excluding patients with hepatic, renal, or cardiac abnormalities may not be justified, given the safety profiles of the study interventions. Of the 97 randomized controlled trials analyzed, 21% had the potential to cause nephrotoxicity. But nearly 74% of the trials excluded patients with renal abnormalities.

“The results relevant to neurological function did not follow this same trajectory,” says Statler. “Our findings indicate exclusion of patients with peripheral neuropathy may not be conservative enough.”

Statler adds, “Our findings suggest clinical research may unintentionally evoke a health equity dilemma.”

Clinical trials are designed to contribute to society’s general knowledge regarding the diagnosis, cure, mitigation, treatment, or prevention of disease. The study’s findings suggest that the studies’ results are only applicable to a select cohort of patients. “These select groups of potential beneficiaries are essentially established by the respective clinical trials’ eligibility criteria,” says Statler.

Many commonly used exclusion criteria may not be appropriate, given the study interventions’ safety profiles. Thus, widespread use might lead to the exclusion of specific groups of patients. “Furthermore, because cancer is a life-threatening disease, access to novel therapies is essential,” Statler says.

Overly restrictive criteria may limit the therapy options for specific patient populations, such as people with organ function abnormalities or comorbidities. “This presents ethical issues related to justice,” says Statler.

REFERENCE

  1. Statler A, Radivoyevitch T, Siebenaller C, et al. The relationship between eligibility criteria and adverse events in randomized controlled trials of hematologic malignancies. Leukemia (7 December 2016) doi:10.1038/leu.2016.374