Is Demand for Trial Subjects Outpacing Supply?

September 1, 2006

Clinical trials may be running out of volunteers, according to a report at the American Society of Clinical Oncology 2006 meeting

ATLANTA—It is a phrase heard increasingly during scientific presentations: "Trial stopped early due to lack of accrual." Clinical trials may be running out of volunteers, according to a report at the American Society of Clinical Oncology 2006 meeting (abstract 6016).

In a review of breast, lung, and prostate cancer studies currently accruing patients, lead investigator Jennifer Tam-McDevitt, PharmD, PhD, of the Geriatric Oncology Consortium, Baltimore, and her colleagues found that 238,000 patients are needed to fulfill enrollment aims for these studies. For breast cancer, the number of patients needed represents a significant percentage of the breast cancer incidence for 2005. Currently, only about 10% of cancer patients are enrolled in US trials. With more drugs in the pipeline and more clinical trials being conducted, demand for participants may be outpacing the current "supply," she said.

The researchers derived data from the Clinical Trials database maintained by the NIH (www.clinicaltrials.gov). This database was selected because it has been proposed as the mandated repository for clinical trials information. Over a 2-month period, the database was mined for all active US trials recruiting patients for phase I, I/II, II, and III clinical trials in breast, lung, and prostate cancers.

The researchers found 290 breast, 212 lung, and 177 prostate cancer trials; the number of patients needed for the trials was 151,311 (breast), 33,498 (lung), and 53,181 (prostate). These figures represent 19.4% to 71.6% of the American Cancer Society incidence estimates of the studied tumors. About half of the studies (51%) were phase II, and about half the patients had advanced disease.

"Although many studies have an anticipated enrollment period over several years, the number of trial participants needed to complete these studies is quite daunting," Dr. Tam-McDevitt said, adding that the results are likely underestimates, as not all studies currently enrolling patients may be included in the NIH registry, and not all studies in the database specified the recruitment goal.

"It is clear that, given the current trial participation rate, demand has outpaced supply," she said. "The number of anticancer agents in the pipeline heading into clinical trials will continue to fuel the competition for research patients."

One solution to the problem, she said, could be rationing patients to important studies. "But more important, we support the creation of a national task force to facilitate better communication with the medical community, the government, the public, and the industry, to address current challenges to study enrollment and retention," she said.

Patients Unaware of Trials

In another ASCO presentation (abstract 6062), investigators maintained that patient unwillingness is not a key factor in insufficient enrollment; more important is the fact that patients may simply be unaware of the opportunity. The study was headed by Robert L. Comis, MD, and his colleagues from the Coalition of Cancer Cooperative Groups, Philadelphia, an organization that lobbies to increase patient and physician participation in trials.

Only 10% of patients are even aware that clinical trials are available to them, according to a web-based survey of attitudes and awareness among 1,788 cancer survivors. For 73% of these subjects, a physician was the source of the trial information. The most awareness was seen among patients with leukemia (26%), and the least among colorectal and bladder cancer patients (3% to 6%). Patients who declined clinical trial participation cited concerns about the new approach being less effective, and about being randomized to the placebo arm. Patients who had participated in clinical trials reported a very high level of satisfaction with the experience: 97% said they felt they were fully informed on risks and benefits; 96% said they were treated with dignity and respect during the trial; 92% said they had a positive experience, and 91% said they would recommend participation to a friend or family member. Only 9% said they felt like a "guinea pig." The results of the survey confirmed that "the cancer clinical trial experience is valued and appreciated by cancer survivors," Dr. Comis said.

Another ASCO report (abstract 6026) suggested that recruitment to ongoing phase III trials might be hindered by the accelerated approval of cancer agents. Andrew J. Lurie, BGS, of Northwestern University, noted that under accelerated approval, novel agents are approved based on improvements in surrogate outcomes, provided that subsequent phase III trials show evidence of clinical benefit (subpart H commitment). "However, drugs that receive accelerated approval must already show promise, making it difficult to recruit for randomized studies in which patients might get other drugs that are likely to be inferior," he said. "Policy makers have raised concerns that these studies are rarely completed."

His study evaluated whether drugs granted accelerated approval were "as likely to be superior as inferior to standard therapy" during the phase III trials, which is a necessary condition for clinical trials known as equipoise—the ethical basis for recruitment. Among 23 agents that received accelerated approval prior to 2004, subpart H commitments have been fulfilled for the 11 indications associated with high-incidence cancers, at a median completion time of 2 years. Of 12 drugs with accelerated approval for low-incidence cancers, only 1 (8.3%) has been converted to regular approval, with a median time from accelerated to regular approval of 6 years, and more than 90% are still being studied 6 years after accelerated approval. The chief reason for the lack of confirmatory studies is slow accrual, he said.

"While the equipoise theory predicts that 50% of the completed phase III trials would support the novel therapy, empirical data show that 90% of the studies required by subpart H commitments support the novel therapy," he said. "Since patients have access to the accelerated-approved drugs, even if they do not enroll in a randomized phase III trial, recruitment to ongoing phase III trials of these drugs is likely to be hindered."