Effect of early patient enrollment on the time to completion and publication of randomized controlled trials

Abstract

The authors evaluated whether early enrollment affects the significance of the results and the time to completion and publication of randomized controlled trials. Seventy-seven efficacy randomized controlled trials (total enrollment, 28,992 patients) initiated by the Acquired Immunodeficiency Syndrome Clinical Trials Group between 1986 and 1996 were evaluated. After adjustment for target sample size, for each 10-fold increase in the first-month accrual, the odds of a trial reaching statistically significant results increased 2.8-fold (p = 0.040). The relative enrollment during the first month over target sample size (hazard ratio (HR) = 1.40 per 10 percent increase, p = 0.004) and masking (HR = 1.78 for double-blind vs. single or unblinded studies, p = 0.031) were the major predictors of faster completion. Rapid early accrual (HR = 1.09 per 10 additional patients accrued the first month, p = 0.011) and statistical significance in favor of an experimental arm (HR = 2.47, p = 0.004) independently predicted faster publication. Early enrollment is a strong predictor of whether a study will reach formal statistical significance, and it can offer predictive information on the time needed to complete the study and publish its findings. Ongoing unpublished studies and their enrollment rates may need to be considered when interpreting the accumulated evidence.