Interventions to increase enrollment in a large multicenter phase 3 trial of carotid stenting vs. endarterectomy

Background Randomized clinical trials often encounter slow enrollment. Failing to meet sample size requirements has scientific, financial, and ethical implications. Aims We report interventions used to accelerate recruitment in a large multicenter clinical trial that was not meeting prespecified enrollment commitments. Methods The C arotid R evascularization E ndarterectomy vs. S tenting T rial began randomization in D ecember 2000. To accelerate enrollment, multiple recruitment tactics were initiated, which included expanding the number of sites, hiring a recruitment director ( M ay 2003), broadening eligibility criteria ( A pril 2005), branding with a study logo, Web site, and recruitment materials, increasing site visits by study leadership, sending e‐mails to the site teams after every enrollment, distributing electronic newsletters, and implementing investigator and coordinator conferences. Results From D ecember 2000 through M ay 2003, 14 sites became active (54 patients randomized), from J une 2003 through A pril 2005, 44 sites were added (404 patients randomized), and from M ay 2005 through J uly 2008, 54 sites were added (2044 patients randomized). During these time intervals, the number of patients enrolled per site per year was 1·5, 3·6, and 5·6. For the single years 2004 to 2008, the mean monthly randomization rates per year were 19·7, 38·1, 56·4, 53·0, and 54·7 (annualized), respectively. Enrollment was highest after recruitment tactics were implemented: 677 patients in 2006, 636 in 2007, and 657 in 2008 (annualized). The prespecified sample size of 2502 patients, 47% asymptomatic, was accomplished on J uly 2008. Conclusions Aggressive recruitment tactics and investment in a full‐time recruitment director who can lead implementation may be effective in accelerating recruitment in multicenter trials.