Clinical trial implementation and recruitment: Lessons learned from the early closure of a randomized clinical trial
ABSTRACT The NHLBI-sponsored Sickle Cell Disease Clinical Research Network (SCDCRN) conducted a multi-center, acute intervention randomized clinical trial of two methods of Patient Controlled Analgesia for acute pain. This trial was terminated early due to low enrollment. We analyzed the perceived barriers and recruitment difficulties as reported by the coordinators and principal investigators.
Participating sites completed a missed eligibility log of subjects admitted in pain crisis throughout the study and a survey at the end of the trial. The survey covered site-specific factors, policies, and procedures in study implementation, recruitment strategies, and eligibility factors. The New England Research Institutes (NERI) collected de-identified surveys from 31 respondents at 29 of 31 participating sites.
From December 2009 to June 2010, 1116 patient encounters for SCD and pain occurred at participating institutions: 38 subjects were enrolled (14 pediatric and 24 adults) and 34 completed the trial, below the projected 278 subjects. Fourteen sites enrolled subjects and seventeen did not. Recruitment barriers included insufficient staff, subject ineligibility or in too much pain to consent, competing protocols, and concerns regarding pain control. Recruitment methods were referrals from urgent care, SCD clinics and in house databases. No use of media or outside physicians was reported.
We identified multiple barriers to patient accrual including short duration of enrollment period, protocol design, complex dosing schedule, requirement for staff availability during week-end and after hours, multiple departments' involvement, protocol acceptance, eligibility criteria, competing protocols, and limited staff. Each of these areas should be targeted for intervention in order to plan and conduct successful future clinical trials.
- [Show abstract] [Hide abstract]
ABSTRACT: Ethical evaluation of risk-benefit in clinical trials is premised on the achievability of resolving research questions motivating an investigation. To determine the fraction and number of patients enrolled in trials that were at risk of not meaningfully addressing their primary research objective due to unsuccessful patient accrual. We used the National Library of Medicine clinical trial registry to capture all initiated phases 2 and 3 intervention clinical trials that were registered as closed in 2011. We then determined the number that had been terminated due to unsuccessful accrual and the number that had closed after less than 85% of the target number of human subjects had been enrolled. Five factors were tested for association with unsuccessful accrual. Of 2579 eligible trials, 481 (19%) either terminated for failed accrual or completed with less than 85% expected enrolment, seriously compromising their statistical power. Factors associated with unsuccessful accrual included greater number of eligibility criteria (p = 0.013), non-industry funding (25% vs 16%, p < 0.0001), earlier trial phase (23% vs 16%, p < 0.0001), fewer number of research sites at trial completion (p < 0.0001) and at registration (p < 0.0001), and an active (non-placebo) comparator (23% vs 16%, p < 0.001). A total of 48,027 patients had enrolled in trials closed in 2011 who were unable to answer the primary research question meaningfully. Ethics bodies, investigators, and data monitoring committees should carefully scrutinize trial design, recruitment plans, and feasibility of achieving accrual targets when designing and reviewing trials, monitor accrual once initiated, and take corrective action when accrual is lagging. © The Author(s) 2014.Clinical Trials 12/2014; 12(1). DOI:10.1177/1740774514558307 · 1.94 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: AimThe aim of this study was to describe nurse leaders’ perceptions of ethical recruitment in clinical research.Background Nurse leaders are expected to get involved in clinical research, but there are few studies that focus on their role, particularly the ethical issues.Method Qualitative data were collected from ten nurse leaders using thematic one-to-one interviews and analysed with content analysis.ResultsNurse leaders considered clinical research at their workplace in relation to the key issues that enabled ethical recruitment of study subjects in clinical research. These were: early information and collaboration for incorporating clinical research in everyday work, an opportune and peaceful recruitment moment and positive research culture.Conclusion Getting involved in clinical research is part of the nurse leader's professional responsibility in current health care. They have an essential role to play in ensuring that recruitment is ethical and that the dignity of study subjects is maintained.Implications for nursing managementThe duty of nurse leaders is to maintain good contact with other collaborators and to ensure good conditions for implementing clinical research at their site. This requires a comprehensive understanding of the overall situation on their wards. Implementing clinical research requires careful planning, together with educating, supporting and motivating nursing staff.Journal of Nursing Management 08/2014; DOI:10.1111/jonm.12248 · 1.14 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: A substantial number of planned clinical trials for sickle cell disease (SCD) have terminated early due to insufficient patient enrollment. To describe attitudes toward clinical trials among a sample of adults with SCD and identify patient-level factors associated with these attitudes. Our data came from a sample (N = 291) of primarily adults with SCD participating in the Improving Patient Outcomes with Respect and Trust (IMPORT) study, which is a federally funded observational study of SCD patient experiences in seeking healthcare. Attitudes toward clinical trials were assessed using items from the Perceptions of Participation in Clinical Research instrument. Patient factors examined as potential correlates of clinical trial attitudes were demographics, disease severity, engagement in self-care, trust, healthcare experience ratings, and prior history of participation in clinical trials. Multiple regression analyses were used to identify patient-level correlates of clinical trial attitudes. Our sample of SCD patients expressed overwhelmingly favorable attitudes about clinical trials, with 77%-92% of our sample expressing agreement with a series of positive statements about clinical trials in general. Demographics, engagement in self-care, healthcare experience ratings, and prior trial participation each explained significant portions of the variability in clinical trial attitudes. The generalizability of our results to the entire SCD population may be of concern as the study participants were all receiving care at comprehensive sickle cell centers and already participating in clinical research. Our results suggest that, in principle, adults with SCD enrolled in an observational study express very positive general attitudes about clinical trial participation and that specific factors attached to particular clinical trial opportunities may play a greater role in a SCD patient's decision to participate than a general unwillingness to participate.Clinical Trials 02/2014; 11(3). DOI:10.1177/1740774513519876 · 1.94 Impact Factor