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, investigators reported Tuesday.
That failure rate represents stalled progress in the pursuit of better cancer drugs and techniques – and “a waste of scarce human and economic resources,” according to a study by Fred Hutchinson Cancer Research Center and the University of Washington.
To help predict which clinical trials may not entice or find a sufficient number of participants, the authors identified several trial-related “risk factors” associated with low patient-accrual rates.
The risk of low patient-accrual is higher, for example, in trials that require a tissue sample or biopsy to determine whether patients are eligible for the trial versus those that do not require such invasive eligibility assessments, the authors found. Another risk factor: when patients know they may not – or will not – be treated with a potentially new drug or therapy they appear much less likely to enroll.
“If you have a trial looking at a new investigational drug, it’s much more likely to hit its accrual target. That’s especially true of Phase 2 trials [testing drug safety], which often guarantee patients will get the new treatment,” said Dr. Carrie Bennette, an investigator with the Hutchinson Institute for Cancer Outcomes Research, or HICOR, and a recent graduate of the University of Washington.
In Phase 3 drug trials, by comparison, patients typically are “randomized,” meaning they randomly receive either cutting edge – if still unproven – treatment or the most effective treatments already approved by the government. Randomization is a cornerstone of clinical trials and is critical to determine which treatment works better, but it has important implications for accrual rates.
“As soon as you add in randomization, where patients may or may not get [the investigational treatment], it wipes away the higher accrual rates we found among trials studying new treatments,” Bennette said.
The findings of Bennette and her colleagues were published in the Journal of the National Cancer Institute.
Clinical trials are regarded as the gold standard to examine if a new treatment is safe and effective in people. To evaluate those benchmarks, statisticians and clinicians calculate how many patients must enroll in clinical trial to draw valid and meaningful conclusions.
The authors analyzed data from 787 Phase 2 and Phase 3 adult trials sponsored by the National Clinical Trials Network (NCTN) between 2000 and 2011. The NCTN is part of the National Cancer Institute.
The Hutch researchers found that 18 percent of cooperative-group-sponsored trials closed due to low patient-accrual rates – or were accruing at less than 50 percent of the targeted participation number three or more years after launch.
No scientific advance
If a trial closes due to low accrual, the patients who enrolled still get the potential treatment under investigation. But the researchers behind the study cannot report whether the drug or therapy actually works, Bennette said.
“What that means is a clinical trial is started, a tremendous amount of resources are invested in designing the trial and finding sites to begin to enroll patients – then that trial doesn’t get used to help advance science or improve clinical practice,” Bennette said.
Another risk factor associated with low participant rates is “increased competition for patients from ongoing trials,” Bennette and her colleagues found. Their work was funded by grants from the federal Agency for Healthcare Research and Quality and the National Science Foundation.
Scientists already struggle to convince cancer patients to join clinical trials. Nationally, only 3 to 5 percent of adult cancer patients enroll in these studies.
And, then, there are highly motivated patients, like Wendy Ramsey, 60, diagnosed with chronic lymphocytic leukemia (CLL).
'I am in awe'
To combat her disease, Ramsey participated in four different trials. Today, she’s nearly four years into a Phase 1 clinical trial initially conducted through Fred Hutch to test a new treatment.
“It has been so very successful for me, I am generally in awe of my life these days,” said Ramsey, who lives in Idaho.
For that trial, she takes three pills daily with no detectable side effects, she said. She cycles, hikes and travels. Her doctor has told her she is in remission.
“As the months roll by, I sometimes stop and remember that I am a cancer patient,” Ramsey said. “Life is that normal. The trial is life changing for me.”
To teach herself how to find and review trials, she painstakingly tapped an online community of CLL patients.
“It taught me that cancer treatment is always a risk-versus-reward decision,” Ramsey said. “… It showed me that cancer patients live in a world with a very high level of hope – because we have to.”
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.
In fact, cancer patients who live on less than $50,000 annually participate in clinical trials at a rate one-third lower than those who earn more each year, experts at Fred Hutch and other institutions reported in October.
“The real issue is still the lack of patients involved in cancer trials, irrespective of whether they are conducted by cooperative groups [like the National Clinical Trials Network], private or single-institution entities, or the pharmaceutical industry,” wrote Raghavan, president of Levine Cancer Institute in Charlotte, North Carolina.
“It is well documented that patients on clinical trials have better outcomes than those who do not participate,” Raghavan wrote. “… We should strive to improve trial enrollment, giving the associated potential for improved results.”
To learn more about clinical trials at Fred Hutch, go here.
Bill Briggs was a former Fred Hutch News Service staff writer as well as a contributing writer for NBCNews.com and TODAY.com. As a staff writer for The Denver Post, he was part of the newspaper's team that earned the Pulitzer Prize for coverage of the Columbine High School massacre. He authored two books, including "The Third Miracle: An Ordinary Man, a Medical Mystery, and a Trial of Faith."
