SAN FRANCISCO—Of the 7,776 adult cancer clinical trials initiated in 2005, approximately 20% failed to complete enrollment for reasons other than toxicity or efficacy of intervention, a study presented at the 2014 Genitourinary Cancers Symposium concluded.
The number one reason: poor accrual.
“The field of bladder cancer is replete with examples of trials that failed to complete,” said Matthew D. Galsky, MD, Director, Genitourinary Medical Oncology, and Associate Medical Director, Cancer Clinical Trials Office, Icahn School of Medicine at Mount Sinai, and The Tisch Cancer Institute, New York, NY. “Such trials require substantial resource expenditure and entail the time, trust, and commitment of patients, yet contribute minimally to the scientific knowledge base and direct recourses from answering critical questions.”
In 2010, the Institute of Medicine reported that approximately 40% of all National Cancer Institute Cooperative Group–sponsored clinical trials were never completed. However, sponsored trials only account for about 15% of all clinical trials. Noting these limitations, and that the scope of this problem had not previously been comprehensively evaluated, the investigators sought to determine the cumulative incidence of trials failing to complete over time, variables associated with studies that failed to complete, and whether genitourinary cancer trials were more likely to fail to complete.
They interrogated the ClinicalTrials.gov dataset for phase 2 or 3 interventional trials registered from September 13, 2005 through November 15, 2011. They used the search term “neoplasm” and then determined whether the key words “terminated” or “withdrawn” were present in the status field.
Of the 7,776 trials, which enrolled approximately 48,000 patients, 491 were in prostate, 142 in kidney, 75 in bladder, and 34 in testis cancers. A total of 935 trials were terminated early. Characteristics of trials failing to complete include those that were industry-funded versus federally funded (hazard ratio [HR], 1.97; 95% CI: 1.57-2.48), single-center versus multicenter sites (HR, 1.93; 95% CI: 1.64-2.27), and phase 2 versus 3 (HR, 1.29; 95% CI: 1.02-1.62). Trials conducted outside the United States or both in and outside the United States were more likely to be completed compared with trials based only in the United States (non-US: HR, 0.65; 95% CI: 0.55-0.77; both: HR, 0.67; 95% CI: 0.51-0.88). Genitourinary cancer trials were not significantly more likely to fail to complete.
“Not only does poor accrual lead to more expensive trials, [and] lead to trials that generate answers much more slowly, but also prevents many trials from generating any answers at all,” said Dr. Galsky. “Clinical trials that fail to complete represent an important barrier to progress in cancer care and this is by no means limited to genitourinary cancer trials but impacts the entire cancer clinical trials center process.”
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In addition to poor accrual (362 trials [38.7%]), reasons for termination included sponsor cancellation (99 [10.6%]), lack of funding (52 [5.6%]), agent unavailable (23 [2.4%]), departure of the principal investigator (18 [1.9%]), results at interim analysis (92 [9.9%]), toxicity/adverse events (77 [8.2%]), other (87 [9.3%]), trial no longer necessary (33 [3.5%]), or no reason given (92 [9.9%]). Dr. Galsky said in determining the number of adult cancer clinical trials that failed to complete, they eliminated toxicity or efficacy of intervention as reasons, as these are outcomes expected from a clinical trial.
“I want to very clearly state that this research is not an indictment of any particular stakeholder,” Dr. Galsky said. “This is not a finger-pointing exercise. As a clinical trialist, I’ve designed and led more than one study that’s failed to complete. Rather, what we wanted to do is hold up a mirror to our activities as a cancer clinical trial community and really ask whether the system is optimized to bring better treatments to our patients as efficiently as possible, and clearly there is some work to do.
“Based on this analysis and others, it’s apparent that we need better collaboration and communication within the system and we need novel approaches to increase accrual to cancer clinical trials, which has really been quite steady at 3% to 5% of the adult cancer population for decades,” he concluded.
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).