Clinical trials struggle to recruit, retain patients

ABSTRACT: An alarming 80% of US trials are delayed because of poor enrollment. Experts share what’s being done to close the gap between patients’ awareness of trials and their actual participation?

It’s no secret that enrollment into cancer care clinical trials has reached a level that could be described as anemic. Conventional wisdom puts adult enrollment at 3% to 5%, even though two-thirds of cancer patients say they are receptive to participating.

“Two surveys of cancer survivors conducted in 2000 and 2005 suggest that 4% is probably a real number,” said Robert L. Comis, MD, president and chair of the Coalition of Cancer Cooperative Groups (CCCG) and chair of the Eastern Cooperative Oncology Group (ECOG). A recent survey of 9762 patients by the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) found only a slightly higher rate, 5.5%.

Either way, the number is “distressingly low,” Dr. Comis said.

The consequence of the lack of enrollment is a crisis in drug development, warned William Gradishar, MD, director of breast medical oncology at the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, in Chicago.

“I spend much of my day talking to patients about clinical trials, and, unfortunately, only a small fraction enroll,” he told Oncology News International. Eighty percent of US trials are delayed because of unfulfi lled enrollment, Dr. Gradishar added.

According to Dr. Comis, approximately 70% of patients say they know about trials, but just 10% see them as a treatment option. “There is a big discrepancy between willingness to participate theoretically and actual participation,” he told Oncology News International.

Charles H. Weaver, MD, founder and CEO of Cancer Consults, which represents trials for 120 cancer clinics, noted “there are barriers in the marketplace, in spite of patient motivation.”

Trialists are trying to close the gap between patients’ awareness of trials and their actual participation. One recent development by the CCCG is TrialCheck, a trial database and matching/eligibility tool that is operated through a website (www.CancerTrialsHelp.org) and the American Cancer Society’s 24-hour call center.

“TrialCheck was designed by clinicians for clinicians to make it easy for oncologists and patients to know which studies are up and running,” Dr. Comis said.

As data from TrialCheck mature, trialists will gain insights into factors influencing participation. Meanwhile, the first eight months of operation have yielded some information (see Sidebar below), as has the CanCORS study.

CanCORS found that patients were more likely to participate if their physician had recently enrolled other patients; their physician practiced at an NCIdesignated cancer center; or the patient was younger than 50 years old, male, not a member of a minority group, or had advanced disease.

Physicians were more likely to enroll patients if they expected fi nancial gain, reported Mona N. Fouad, MD, MPH, of the University of Alabama at Birmingham.

While these efforts to boost trial participation are laudable, Dr. Weaver, who helps cancer patients fi nd trials, still has concerns about how trials are perceived.

“Patients still look at trials as a ‘value proposition’ and are most interested in the outcome to be achieved,” he said. “If you take all the barriers away, without off ering a trial that will change their personal outcome, I doubt the situation will change much.”

Trial attraction

There is a direct relationship between the patient’s perception of a trial and the doctor’s interest in the same, Dr. Comis pointed out. “If physicians encourage patients to enroll, they generally do. Our hope is that if patients become more active about searching for trials, doctors will respond by providing them.” Dr. Weaver agreed, noting that patients primarily want to fi nd the “best” oncologist and put their faith in him or her, rather than the therapy.

What can be done to facilitate involvement among oncologists? According to Dr. Comis, clinicians should be attracted to the cutting-edge research.

“The most interesting trials involve novel approaches or give physicians access to new medications before they are generally available. Th is should be a major advantage to clinicians,” he said.

Laurence H. Baker, DO, chair of the Southwest Oncology Group in Ann Arbor, Mich., agreed that oncologists participate when they are interested in the question being addressed. “Th is means they believe the best medicine can be practiced within the context of a clinical trial, with the subtext being that they have greater access to novel agents,” he said.

‘Not a money-making operation’

But don’t count on a financial payoff , interviewees said. “Clinical research is not a money-making operation,” Dr. Comis noted. “At least half the patients enroll on the public side through the cooperative group system, which is grossly underfunded.”

Costs have risen while the NCI budget has remained flat. “In the cooperative group system, we peaked at $150 million in funding, which is now down to $145 million. Adjusted for inflation, this is a decrease of 20%,” he said. “Reimbursement by the NCI is $2,000 per case, although the average cost is more like $4,000. The sites that are most successful economically have strong institutional commitment and survive by doing a mix of public and private trials. On the private side, clinicians can at least break even.”

Dr. Comis noted “it’s amazing that committed physicians continue to enroll patients. It’s not easy to do clinical research, but, no question, there are success stories, and trial participation can be made into a marketing advantage.”

Indeed, some claim there is actually an economic disincentive to trial involvement, since oncologists can bill more for chemotherapy than they receive for enrolling a patient. “Physicians may tend to enroll those patients who lack good health insurance,” Dr. Weaver pointed out, though this may be changing. “As margins are diminishing, trials are becoming more economically advantageous.”

Dr. Baker added that research universities also feel the pinch, since they cannot fund their research with NIH grants alone but must rely on revenue derived through clinical practice.

“This comes from the same physicians who are counted upon to do the trials,” he said, adding that the effort required for conducting clinical trials is “contrary to the university’s business interests.”

Easing the burden of trials Policy issues on the front burner may lead to change. Efforts are being made to shorten the period between trial inception and enrollment (currently two to three years) and to convene leadership councils to set research priorities and align strategies among organizations that will be “complementary and not antagonistic,” Dr. Baker said.

Discussions are under way to “harmonize the missions of the cancer centers and the cooperative groups,” he explained. According to Dr. Baker, cancer center guidelines permit involvement only in phase I and phase II studies and not in phase III cooperative group trials.

“Everyone involved in this process recognizes that inequity and is trying to change it,” he said. “Some cancer centers have the courage to say, ‘This policy is obviously wrong,’ and they endorse participation in cooperative group studies anyway. Others say, ‘This is not our job.’ But I contend it is the mission of a cancer center to conduct scientifically rigorous activities. The most important clinical trials are those that change the practice of medicine: the phase III trials.”