Effects of randomizing second eyes in a trial to evaluate preoperative medical testing for cataract surgery

Abstract

The statistical and practical implications of including second eye surgeries were examined in a clinical trial designed to evaluate the impact of routine preoperative testing prior to cataract surgery on major medical events occurring within seven days following surgery. In order to detect a 0.8% difference in the rates of rare major medical events between the tested and untested groups, 20,000 surgeries must be randomized. About 30% of cataract operations were estimated to be done on second eyes of patients already included in the cohort. Different options for dealing with second eye surgeries were: (1) exclusion of all second eye surgeries, (2) inclusion of second eye surgeries only if the first eye is not enrolled, (3) inclusion of first and second eyes but randomization of patients rather than eyes, and (4) inclusion of first and second eyes but randomization of surgeries rather than patients. The final decision was to exclude second eye surgeries done within 28 days of first eye surgeries, but to rerandomize all other second eye surgeries. Differences in event rates between treatment groups can be estimated using Generalized Estimating Equations, and the association between outcomes of first and second eye operations estimated with pairwise odds ratios. An anticipated small positive correlation is likely to have minimal impact on statistical power and effective sample size.