Eligibility Criteria for Clinical Trials Could Be Loosened, Study Suggests

Patients given waivers to participate in A trial had outcomes the same or slightly better than people who met the standard requirements; findings support broader and more inclusive trial designs. 

Cancer patients sometimes find it difficult to get into clinical trials because of strict eligibility criteria. A new study from Europe indicates that patients could benefit from loosened requirements for participation. 

Patients who didn’t qualify for a trial under standard criteria but were allowed to participate via a waiver had the same or slightly better outcomes than those who met the criteria, according to the results of the study. 

“Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial,” said Hans Gelderblom, MD, senior author of the study and chair of the Department of Medical Oncology at the Leiden University Medical Center in the Netherlands.

Eligibility requirements for clinical trials help protect patients whose comorbidities may put them at an additional risk of severe harm from the treatment being tested. Further, they help ensure that analyses are performed on a carefully controlled population, minimizing outliers that could skew the data. 

Exemptions are sometimes granted to allow patients to participate in trials for which they would otherwise be ineligible. Examples of such exemptions include lab tests slightly outside the eligibility range, a necessary imaging scan completed outside the recommended window, or a tumor that could not be biopsied for safety reasons, Dr. Gelderblom explained. Whether these exemptions—or, by extension, the broadening of clinical trial eligibility criteria—lead to poorer patient outcomes has not been comprehensively studied, Dr. Gelderblom said. 

Dr. Gelderblom and colleagues studied the outcomes of patients participating in a trial that tested new options for cancers that didn’t respond to standard treatment. The trial, called the Drug Rediscovery Protocol (DRUP), matched patients with off-label targeted therapies based on the genetic profile of their particular tumor. Between September 2016 and September 2021, the 1,019 patients enrolled in the DRUP trial included 82 patients who received a protocol waiver.

The reasons for waivers were grouped into four categories: eligibility criteria exceptions, out-of-window testing, treatment exceptions, and testing exceptions. The waivers most commonly granted were exceptions to eligibility criteria, often due to out-of-range lab tests. The second most common waivers granted were testing exceptions, often exemptions from a biopsy. 

At 16 weeks post-treatment, the clinical benefit rate was 40% among patients who received a protocol waiver, compared to 33% among patients who did not receive a waiver. Similarly, the median overall survival among patients who were and were not granted waivers was 11 months and 8 months, respectively. 

Patients who received waivers were also no more likely to experience severe adverse events (SAEs) than patients who did not receive waivers; SAEs were observed in 39% of patients granted a waiver and 41% of patients without waivers.

Dr. Gelderblom and colleagues also evaluated the likelihood that each SAE was caused by a protocol waiver in patients who received them. They deemed the relationship between waivers and SAEs “unlikely” for 86% of patients and “possible” for 14% of patients. The rates of treatment discontinuation due to toxicity or progression during the first treatment cycle were similar among patients who did and did not receive waivers. 

While the protocol exceptions studied in this trial were minor, Dr. Gelderblom said, they could have broader implications for the design of clinical trial eligibility criteria. 

“These findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” he said.