Clinical Trial Accrual Hampered by Many Factors

In recent years, cancer patients are more knowledgeable and willing to participate in clinical trials, but issues pertaining to physician enthusiasm, design requirements, and enrollment procedures now pose large barriers to patient accrual, finds two new Cancer studies. Since previous research has predominantly focused on patient and physician perspectives, Canadian researchers interviewed clinical research associates (CRAs), whose work spans all stages of clinical trials, to gain new insight into the factors influencing enrollment. The CEO of an Austin, Texas-based contract research organization (CRO), which designs trials and staffs CRAs, told the Watch (9/24/02) that the strict participation guidelines for oncology-related clinical trials make meeting accrual goals for experimental cancer therapies particularly difficult.

CRAs say patients still reluctant to participate, but better informed

Eva Grunfeld and colleagues conducted focus groups of CRAs because their “unique perspective” on gaining patient consent, day-to-day trial administration, and analyzing results has been “rarely” explored (Cancer, 10/1/02). Twenty-nine clinical workers at six tertiary care centers in Ontario, Canada, told investigators they believed volumes of extra tests and questionnaires, the potentially greater toxicity of an investigational treatment, and the extra stress of participation hindered patient enrollment efforts. However, heightened media coverage and the Internet appear to have improved patient awareness and interest in clinical trials. CRAs reported that more informed patients believe trials offered better treatment options than standard procedures, a potential cure for their cancer, and increased care from medical staff. Increased awareness raises the population of potential study candidates, CRAs told researchers, therefore facilitating the recruitment process.

While physicians influence recruitment…

Increased patient interest in clinical trials represents a significant step toward improving accrual, but oncologists, who initially discuss treatment options with patients, remain the ultimate “gatekeepers” of clinical research. A second Cancer (10/1/02) study, led by Dr. James Wright of the Ontario-based Hamilton Regional Cancer Centre, explored CRAs' perceptions of factors that influenced a patient's decision to enter trials. Two CRA focus groups indicated that physicians who provided prospective participants with a “sound rationale” for enrolling in clinical trials significantly improved accrual efforts. They believed the level of the referring oncologist's belief in the potential benefits of an experimental new treatment plays a direct role in shaping their patients' minds when discussing the prospect of trial participation. CRAs thought only principal investigative physicians consistently exhibit such “enthusiasm,” because they hold a “vested interest” in their study, often going “the extra mile” during the brief time they may allocate to “identifying and approaching” study candidates.

…redefining CRAs' roles could improve accrual

In clinical studies in which CRAs play a greater part in patient recruitment, they believed their ability to take an “emphatic” and “personalized” approach to gaining consent considerably improved recruitment prospects. CRAs believed recruitment improved when they “honestly and completely presented the pros and cons of study entry to the patient.” They also felt that spending "quality time" with patients, which oncologists could not often afford because of their busy schedules, helped shrink physician responsibility for recruitment. Wright states that his facility has seen accrual improvements by placing increased reliance on CRAs, not physicians, to formally gain patient consent for enrollment in phase III clinical trials.

Rigid trial guidelines limit potential candidates

Despite a better understanding of recruitment hurdles, meeting accrual goals is no small feat. Trial requirements designed with narrow enrollment qualifications limit potential candidates, said Steven Mayo, founder and CEO of Emissary, a CRO dedicated to managing trial design, recruiting patients, and monitoring clinical progress in collaboration with trial sponsors (Watch interview). He said diverse endpoints of cancer therapy trials such as prevention, treatment, increasing survival rate, and improving quality-of-life, further limit potential study population candidates.

 Health Care Advisory Board - October 4, 2002