Why failure rates of randomized clinical trials in radiation oncology are increasing
Randomized clinical trials (RCTs) in oncology have been trending more toward failure than success in recent years, according to research out of Ontario, Canada. But when looking at both ends of the spectrum, behavioral radiation therapy studies are more likely to succeed than those with one or more surgical arms, which fail around 75 percent of the time.
According to a 2010 report from the Institute of Medicine, 40 percent of clinical trials supported by the National Cancer Institute fail to be completed and published, first author Timothy K. Nguyen, MD, and co-authors wrote in the International Journal of Radiation Oncology, Biology, Physics. Those failures don’t come cheap—the average cost of conducting a phase 3 clinical trial from protocol approval to manuscript publication is $21.4 million and can involve more than 370 separate processes.
“Along with wasting time, effort and resources, failed clinical trials subject patients to the risks of trial participation without the intended beneficial results,” Nguyen, of the department of radiation oncology at London Health Sciences Centre in Ontario, and colleagues said. “In addition, clinical trials often compete to recruit from a limited pool of eligible patients, and patients enrolled in a failed trial may lose the opportunity to participate in other trials.”
The authors said there’s been little research into the instigators behind trial failure, which is somewhat surprising considering randomized clinical trials and their meta-analyses are considered the highest level of evidence for intervention.
“Given the negative consequences of incomplete RCTs, minimizing the risk of failure should be a priority,” they wrote.
Nguyen and his team reviewed ClinicalTrials.gov to identify a pool of 134 studies involving radiation therapy between 2007 and 2010. Of those trials, all of which mandated external beam radiation therapy in at least one arm of the study, 70 percent were successful and 30 percent failed.
The most common reason behind trial failure was lack of accrual, the authors wrote, which was the case 57.5 percent of the time. Another 15 percent of failures were attributed to inadequate funding, 7.5 percent to drug unavailability and 7.5 percent to interim data-monitoring report recommendations.
More trials have failed to meet completion over time, according to the study—while RCT failure rates hovered around 12 percent before 2007, by 2012 they’d reached nearly 40 percent. The greatest predictors of failure were trials with a surgical comparator, government sponsorship and inclusion of a safety endpoint. While surgical trials were strongly predictive of failure, Nguyen et al. said, behavioral trials were strongly predictive of success.
“Since success rates for surgical comparator trials were poor, our findings strongly suggest that novel methods should be considered in the design of radiation therapy RCTs with a surgical comparator,” they wrote. “Part of the challenge in comparing surgical procedures with nonsurgical interventions, such as radiation therapy, is that they are starkly different in their nature and toxicity profile, resulting in strong patient and provider preferences for one over the other. Patients may have preconceived treatment preferences and an unwillingness to accept the uncertainty of randomization.”
The authors said novel study methods could help raise the rate of study completion, as could a qualitative assessment of factors that contribute to the overwhelming success of behavioral studies.
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.