Clinical trial implementation and recruitment: Lessons learned from the early closure of a randomized clinical trial

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Trends in characteristics of cardiovascular clinical trials 2001-2012

“…9 Often, clinical trials fail to meet recruitment targets and many studies report that the period for accrual was extended or prematurely terminated. [10][11][12] Our results show that the enrollment rate dropped from 1. Industry (P = .10) and mixed funding (P = .029) has declined over time, whereas government funding has been stable (P = .54).…”

“…The number of countries involved in multiregional trials trial ranged from 2 to 52 (median 13, IQR 6-24). Over time, multiregional trials involved more countries, from 12 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) in 2001-2003 to 18 in 2009-2012 (P for trend = .031) ( Figure 5B). Importantly, the proportion of sites from Western Europe significantly decreased over time, whereas that of Eastern European, Central/South American, and sites outside Europe and the Americas significantly increased (Table I).…”

Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease

“…[20] A verbal overview of GTT could be supplemented with detailed printed or web-based information consisting of a combination of text, charts, and pictures to describe the process in a stepwise manner. Participants in the current study responded favorably to a brochure developed with this approach.…”

Unsuccessful trial accrual and human subjects protections: An empirical analysis of recently closed trials

“…Abortive studies also poorly utilize scarce human and material resources, and deplete the supply of eligible candidates for other investigations. [8][9][10] Accrual effectiveness once a trial is initiated thus has important implications for safeguarding the welfare of human subjects and the broader research enterprise. We used the clinical trial register clinicaltrials.gov to determine the volume of initiated trials that are unable to attain a meaningful sample, to examine the relationship between unsuccessful accrual and trial closure, and to identify factors that may confer risk of unsuccessful accrual.…”