Almost one-fifth of adult cancer clinical trials fail to reach completion for reasons unrelated to efficacy or adverse effects, according to data being reported at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. Poor accrual is the leading cause.
Trials were more likely to fail completion if they were phase II, single center, funded by industry, or conducted solely in the United States. Trials among patients with genitourinary cancers were no more or less likely to fail than trials among patients with other cancers.
"These findings really underscore the clinical trial accrual problem that we have in the United States. Not only does poor accrual lead to more expensive trials and trials that generate answers much more slowly, but it also prevents many trials from generating answers at all," senior author Dr. Matthew D. Galsky, director of the genitourinary medical oncology program, Icahn School of Medicine at Mount Sinai, New York, said in a press briefing at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.
Dr. Matthew Galsky
The study is not meant to indict any specific stakeholders, Dr. Galsky stressed. "Rather, what we wanted to do was hold up a mirror to our activities as a cancer clinical trials 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 to use 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."
"This is a really interesting presentation which casts some light on one of the major frustrations that I think ... our whole community shares in designing and implementing clinical trials," said press briefing moderator Dr. Charles J. Ryan, leader of the genitourinary medical oncology program at the University of California, San Francisco. "Hopefully, this may be the beginning of a broader discussion that helps improve some of the efficiencies here."
Dr. Galsky speculated that the explanation for poor accrual is multifactorial. "Clearly, we need to engage patients more in the design of trials. We need to design trials that are more pragmatic; eligibility for trials is often so restrictive that only the patients who are the fittest and represent kind of an extreme of cancer patients can actually enroll," he said.
Other issues likely include financial barriers (such as whether insurers reimburse the costs of care for patients in trials); geographic accessibility; and the time and regulatory burdens of participating, especially as they affect community oncology practices. "Addressing the cancer clinical trials enterprise at large requires making the burden of participation lower because that does address accrual, that does address generalizability, that does address accessibility. It’s a problem that needs to be part of this conversation," Dr. Galsky maintained.
Dr. Ryan, the moderator, cited rapid treatment advances as yet another possible reason for poor accrual. "Some trials may take 2 or 3 years to accrue. During the first year, the standards of care may be one thing, and during the third year, the standards of care may have changed. We are really seeing very rapid evolution in our standards of care, so that could be one issue," he elaborated.
Introducing the study, Dr. Galsky noted that trials that fail to complete (that is, close without enrolling the intended number of patients) represent a major inefficiency of the cancer clinical trials enterprise. "Such trials contribute little knowledge, waste finite resources, and potentially divert patients from participating in other trials," he said.
The Institute of Medicine previously issued a report suggesting that about 40% of trials sponsored by the National Cancer Institute fail to achieve completion. But such trials account for only about 15% of all cancer trials.
The researchers analyzed 7,776 phase II or III interventional adult cancer clinical trials registered on ClinicalTrials.gov that had start dates between 2005 and 2011. They searched for those that had failed to reach completion, meaning that the trial had been stopped and had a "terminated" or "withdrawn" status.
The trials had a total of about 48,000 patients. Overall, 10% were trials in prostate, kidney, bladder, or testicular cancer.
The cumulative incidence of failure to reach completion for reasons unrelated to the efficacy or safety of the intervention was about 20%, according to Dr. Galsky.
Among all noncompleted trials, the largest share, 39%, failed to achieve completion because of poor accrual, topping other reasons such as logistics and efficacy/safety.