End Overly Strict Eligibility Criteria for Cancer Clinical Trials

It’s time to end overly restrictive eligibility criteria for cancer clinical trials, says Mikkael Sekeres, MD, MS, Vice Chair for Clinical Research at Cleveland Clinic Cancer Center.

To prove this assertion, he and colleagues recently published an analysis of a decade of leukemia clinical trials comparing outcomes of ineligible and eligible patients in Blood. Their results show that eligibility criteria unrelated to potential drug efficacy or safety, and especially those associated with missing documentation and other administrative errors, can be relaxed.

Study design and results

Dr. Sekeres and colleagues analyzed patients enrolled in SWOG phase 2, 2/3 or 3 protocols open since 2005 for eligibility status, reasons for eligibility, baseline characteristics, serious adverse events (SAEs), Eastern Cooperative Oncology Group (ECOG) performance status (PS), complete remission (CR) and overall survival (OS). They divided 2,361 patients from 13 studies into three groups and compared the latter two:

• Ineligible and excluded from SWOG analyses
• Ineligible but treated in the study and included in analyses
• Eligible and included in analyses

Seventy-eight patients were deemed ineligible and excluded from analyses. The majority of these (73 percent) did not have the disease of interest. Sixty percent of the 169 patients ineligible but included in analysis were deemed so due to missing documentation. Other reasons included lab values (16 percent) or bone marrow biopsy (9 percent) outside of the protocol-defined time window.

The baseline characteristics of ineligible and eligible patients were similar, including the proportion of patients with ECOG PS 2 or higher (OR = 0.60, 95% CI (0.32, 1.15), P = 0.12) and the rate of grade 5 SAEs (OR = 0.69, 95% CI (0.17, 2.99), P = 0.62).

Differences in CR rates between the groups were essentially similar across studies, and multivariable and univariate analysis found no difference in OS between the groups across all protocols (P = 0.25). “When we analyzed overall survival among all patients and controlled for factors like age, sex, study design and disease, we found no association between eligibility status and overall survival,” adds Dr. Sekeres.

A major statement

Relaxing non-essential, administrative criteria is key to increasing clinical trial enrollment, argues Dr. Sekeres. “Fewer than five percent of adult cancer patients are enrolled into clinical trials, and twenty percent of public studies shut down because of low enrollment,” he says. “Why are we exacerbating the problem?”

This study is the first step in removing organizational level barriers to patient enrollment. “Our results show that common reasons for ineligibility like missing documentation don’t impact the rate of toxicities, remission and survival,” says Dr. Sekeres.

He and colleagues recommend the modification of SWOG trial criteria as their findings suggest a potential 10 percent increase in accrual from this step alone. “If correlative testing is not a primary endpoint, why not remove sample collection mandates? When the science makes sense, why not extend the typical timeframe for labs and biopsies?” asks Dr. Sekeres.

Ultimately, more patients enrolled will mean greater and faster access to novel treatments for all patients. “This is about getting better treatments to more patients faster, without any negative impact on study integrity or patient outcomes,” says Dr. Sekeres. “It’s a critical step in the right direction.”