Strategies for Recruitment and Retention of Participants in Clinical Trials

Abstract

CLINICAL TRIALS AND THE CONSEQUENT BENEFITS TO society are in jeopardy in the United States because of a decline in the ability to recruit patients in a timely manner to trials addressing key clinical issues. Current initiatives (eg, the Clinical Trials Transformation Initiative and the proposed National Center for Advancing Translational Sciences) and the recent Institute of Medicine report each recognize that successful recruitment and retention of participants in clinical trials is critical for improving the efficiency and effectiveness of phase 3 and 4 clinical trials and that action to ensure adequate enrollment is urgently needed. Too often trial enrollment fails or is significantly delayed, leading to substantial additional costs to the sponsor. Of particular concern is the failure of US trials to meet desired participant enrollment and the trend toward increasing emphasis on recruitment abroad. The National Heart, Lung, and Blood Institute (NHLBI) and cosponsors convened a workshop on December 7 and 8, 2010, in Bethesda, Maryland, to review, compile, and recommend successful recruitment and retention strategies in phase 3 and 4 clinical trials. Barriers to successful recruitment and key recommendations were discussed, including policies, guidelines, and reimbursement for studies involving human research participants and clinical trial enrollment experience and practice. Seventy-five participants included clinical researchers, private advocacy groups, federal sponsors, regulatory agencies, and industry. Several critical barriers to successful recruitment were identified. First, the importance of health care professionals as gatekeepers for clinical trial participation cannot be overstated. However, many clinicians are either not aware of active trials or do not refer their patients for participation in trials. Some have questioned the ethics of physicians involving their own patients in clinical trials, whereas others note the challenge of achieving equipoise when physicians have firm opinions about treatment choices. This is compounded by patients’ lack of knowledge about clinical trials for which they may be eligible, availability of experimental intervention in the community, and entrenched cultural and historical views and suspicions of clinical research. Second, the financial realities of funding clinical trials must be estimated accurately and met. Understated infrastructure needs or reimbursement costs associated with recruitment and retention can lead to failure. Substantial costs are necessary to enroll and retain diverse populations, and these additional costs compete for available funds in a fiscal climate in which cost containment is expected. Women and minority populations are more difficult and more costly to recruit and retain in trials because, for women, the costs of child care, transportation, and even usual health care are often out-of-pocket additional expenses for their participation. For minorities, extra time is needed to gain individual and community acceptance. Balancing the need to enroll these understudied populations and developing outreach strategies to support their participation is an ongoing challenge. Third, administrative burdens and regulatory requirements present unprecedented challenges, even for experienced trialists. Institutional policies that govern clinical investigation often create barriers for clinician investigators rather than encouraging their participation. Moreover, the entire concept of indirect costs related to clinical trials needs review, critical analysis, and optimization. Clinical trials are essential to evaluate new therapies and improve health care. Successful enrollment is pivotal for the success of every trial. The following are recommendations to help promote enrollment success.