One in five cancer trials fails to complete enrollment

Approximately 20% of all cancer trials terminated early, according to findings presented at the 2014 Genitourinary Cancers Symposium.

Perspective from Charles J. Ryan, MD

“Clinical trials are the cornerstone of progress in cancer care,” Matthew Galsky, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai and the director of the Genitourinary Medical Oncology Program at Tisch Cancer Institute, said during a press conference. “Prior to integration into standard practice, new treatments must be tested in a rigorous fashion to determine their relative risks and benefits. Given their critical role, it’s important that the efficiency of the cancer clinical trial enterprise be optimized. Therefore, it goes without saying that clinical trials that are initiated but that fail to complete…represent an extreme example of inefficiency in the system.”

Galsky and colleagues used CancerTrials.gov to identify 7,776 interventional phase 2 and phase 3 adult cancer trials registered between 2005 and 2011. The trials included 491 prostate, 142 kidney, 75 bladder and 34 testis cancer trials.

Of those trials, 935 failed to complete enrollment. Researchers calculated a 20% (95% CI: 18-22%) risk that an adult cancer clinical trial initiated between 2005 and 2011 would fail to complete enrollment.

The most common reasons for early termination were poor accrual (38.7%), sponsor cancellation (10.6%), results at interim analysis (9.9%), toxicity/adverse events (8.2%) and other (9.3%). No reason was given for 9.9% of early trial terminations.

“Importantly, we censored trials that closed because of reasons related to lack of effectiveness or side effects of the intervention, reasoning that these are actually good reasons for a trial to close, and do contribute knowledge,” Galsky said.

Researchers were initially interested in exploring this issue in a comprehensive manner after observing a series of clinical trials in bladder cancer that failed to complete, leaving the field without answers to critical questions regarding how to best care for patients, Galsky said. However, in their analysis, they found that bladder cancer trials — and other genitourinary cancer trials — were not more likely to fail to complete enrollment than trials throughout the entire cancer clinical trials enterprise.

They also found industry-funded trials were more likely to terminate prematurely (HR=1.98; 95% CI, 1.58-2.49), as were trials conducted at a single center (HR=1.93; 95% CI, 1.64-2.27).

Trials were less likely to terminate early when they were conducted outside of the United States (HR=0.65; 95% CI, 0.55-0.77), or within and outside the United States (HR=0.67; 95% CI, 0.51-0.88).

“A large proportion of adult cancer clinical trials fail to complete,” Galsky said. “Between 2005 and 2012, approximately 48,000 patients were enrolled on such trials. Poor accrual was the most common reason, and these findings further understate the clinical trial accrual problem that we have in the United States. Not only does poor accrual lead to more expensive trials, it leads to trials that generate answers much more slowly, and also prevents many trials from generating any answers at all.”

For more information:

Stensland KD. Abstract #288. Presented at: 2014 Genitourinary Cancers Symposium; Jan. 30-Feb. 1, 2014; San Francisco.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Charles J. Ryan, MD

This is a really interesting study that casts some light on one of the major frustrations our whole community shares about designing and implementing clinical trials. Hopefully this may be the beginning of a broader discussion that helps improve some of the inefficiencies.

One of the issues that may be really hard to quantify is the effect of changes in the field overall on ongoing trials. Some trials might take 2 to 3 years to fully accrue. During the first 2 years, the standards of care might be one thing, and during the third year, the standards of care may have changed. We’ve really seen a very rapid evolution in our standards of care. That could be one issue, and there are likely to be others.

Clearly money is also involved, but money can imply a lot of different things. Really, it’s about resources as opposed to just money. Sometimes the resource issue has to do with the work that has to go into the trial before it opens to accrual, and sometimes those delays — due to lack of money or resources — make the trial less relevant when it opens up than we thought it would be when we started planning it. There are a lot of factors there, but the cost of phase 3 trials in particular is into the tens to even hundreds of millions of dollars for corporate sponsors. There’s no question that there has to be a financial component.

But it’s great that we’re having this discussion. It’s not necessarily an issue due to attitudes of patients or clinicians, there are a number of different factors, and it’s great to start looking into this question.

Charles J. Ryan, MD

Professor of clinical medicine and urology

Helen Diller Family Comprehensive Cancer Center

University of California, San Francisco

Disclosures: Ryan reports an advisory board role with Astellas and honoraria from Janssen.