Recruiting subjects for acute stroke trials - A meta-analysis

Background and Purpose - Recruitment rate is a major determinant of the duration, cost, and feasibility of acute stroke trials. Methods - We performed a meta-analysis of all randomized, controlled trials of >= 300 subjects that were designed to evaluate the efficacy of a medical intervention for the treatment of acute ischemic stroke. Data about trial recruitment, organization, and inclusion/exclusion criteria were abstracted independently by 2 reviewers who applied predefined criteria. Recruitment efficiency was defined as the number of subjects enrolled per study center per month of recruitment. Results - Of 32 trials meeting inclusion criteria, the average recruitment efficiency was 0.79 subjects per center per month (range 0.08 to 3.7). Recruitment efficiency did not vary by geographic region (P = 0.36), but trials conducted in 1 country had more efficient recruitment than international studies (P = 0.03), and recruitment efficiency declined with each percentage increase in the total number of study centers (P = 0.002). The primary study entry criteria that predicted reduced recruitment efficiency were the maximum allowable time from stroke to study enrollment (P = 0.002) and the exclusion of mild strokes (P = 0.009). Trials with a treatment window >6 hours had approximately double the recruitment rates of trials that used treatment windows <= 6 hours (1.03 versus 0.52 patients per center per month). Conclusion - Recruitment rates for acute stroke trials are influenced by organizational structure and study entry criteria. Characterizing predictors of recruitment may help optimize future trial design.