One in four cancer trials fails to enroll enough participants

According to a study published on December 29 in the JNCI: Journal of the National Cancer Institute, a number of measurable trial characteristics are predictive of low patient accrual. Nearly one in four publicly sponsored cancer clinical trials fail to enroll enough participants to extract valid conclusions regarding treatments or techniques.

Such trials constitute to an absolute waste of scarce human and economic resources and contribute little to medical knowledge. Clinical trials are the scientific soul of cancer-cure advances, but nearly 20 percent of these publicly funded studies fail to draw enough patients to render verdicts on experimental therapies.

Although many studies have investigated the perceived barriers to accrual from the patient or provider perspective, very few have taken a trial-level view and asked why certain trials are able to accrue patients faster than expected while others fail to attract even a fraction of the intended number of participants.

Some trials do get filled and a paper in the JNCI: Journal of the National Cancer Institute, says there are a number of measurable trial characteristics are predictive of low patient accrual. Scholar’s analyzed information on 787 phase II/III clinical trials sponsored by the National Clinical Trials Network launched between 2000 and 2011.

Caroline S. Bennette, M.P.H., Ph.D., of the Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, and colleagues from the University of Washington and the Fred Hutchinson Cancer Research Center analyzed information on 787 phase II/III clinical trials sponsored by the National Clinical Trials Network (NCTN; formerly the Cooperative Group Program) launched between 2000 and 2011. Bennette et al. found that 145 (18%) of NCTN trials closed with low accrual or were accruing at less than 50% of target accrual 3 years or more after opening.

Factors associated with poor accrual were increased competition for patients, planning to enroll a higher proportion of the available patient population, and not evaluating a new investigational agent or targeted therapy.

The researchers conclude that “Systematically considering the overall influence of these factors could aid in the design and prioritization of future clinical trials…” and that this research provides a response to the recent directive from the Institute of Medicine to “improve selection, support, and completion of publicly funded cancer clinical trials.”

Using 13 predictors for accrual of participants — number of competing trials, phase of trial, enrollment as percentage of eligible population, targeted therapy, radiation therapy, tissue sample requirement, investigational new drug, metastatic setting, sample size, more than one condition evaluated, common solid cancer, and interaction term — the researchers created an algorithm predicting how a study may fare in its recruitment efforts.

“We identified multiple characteristics of cooperative group-sponsored trials that were importantly not associated with low accrual, several of which have not been previously empirically described,” the researchers wrote. “Systematically considering the overall influence of these factors could aid in the design and prioritization of future clinical trials and therefore provides a direct response to the Institute of Medicine’s call for efforts to improve the selection, support, and completion of publicly funded cancer clinical trials.”

For many other cancer patients, however, clinical trials are not an option due to an array of enrollment barriers, including health-insurance constraints, the distance they live from cancer centers, and various “disparities in cancer care,” writes oncologist Dr. Derek Raghavan, in an editorial accompanying the new research by Bennette and colleagues.