Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer

Abstract

Objective The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. Methods We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Results Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. Conclusion A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

“…Randomized chemoprevention trials using agents similar to readily available over-the-counter supplements present unique challenges to recruitment and retention (63). Although several infrastructure, protocol-related and personal factors were taken into consideration while designing the clinical trial, safety monitoring imposed by the FDA continued to challenge recruitment and retention.…”

Chemoprevention Trial Feasibility Using Botanicals in Exceptionally High Risk Populations for Lung Cancer

“…These challenges are significantly associated with protocol and patient-related factors, including the behavioral dynamics of the research team, institutional infrastructure, community and participating subjects [14]. Although other research teams [8,16] have examined feasibility of strategies used to recruit former smokers in chemoprevention trials, these strategies remain costly, not targeted to specific populations nor contemporary. Once the target population, the source of subjects and agent to be evaluated have been identified, it is critical for research teams to carefully examine the potential challenges and facilitators unique to the target population, study agent and disease site as a first step of the design phase of a lung cancer chemoprevention trial.…”

“…However, unlike other trials with experimental drugs or vitamins and minerals, chemoprevention trials using botanicals present unique challenges to recruitment 12. We and others have observed several barriers to recruitment in chemoprevention trials using botanicals including research environment, protocol and subject related factors [16]. Although institutional databases, mass media and community outreach efforts to recruit participation in clinical trials have demonstrated success in epidemiological studies and treatment trials, we have not experienced the same success in recruitment to early phase trials with FDA approved botanicals [14,15].…”

“…In addition to ensuring agent effectiveness, safety and committed academic physicians, the ability of research teams and institutions to recognize subject-related factors is critical to recruiting eligible subjects in chemoprevention trials, who are willing to adhere to study agents and protocols, particularly in randomized clinical trials with botanicals that are easily accessible over- the- counter [14-16]. It is therefore important for research teams to evaluate the feasibility and willingness of specific target populations to participate in these trials, prior to initiating these clinical trials.…”

Safety and Chemopreventive Effect of Polyphenon E in Preventing Early and Metastatic Progression of Prostate Cancer in TRAMP Mice

“…Although several early clinical trials have been initiated using Polyphenon E, including our clinical trial in progress, based on the available data from preclinical studies, restrictions to eligibility imposed by the FDA continue to place a significant challenge on recruitment of subjects to these trials. (5, 51)…”