Hypothesis Testing Problems in an Unbalanced Longitudinal Ophthalmology Study
Communications in Statistics: Theory and Methods
Interaction; missing data; Nonparametric bootstrap test; Repeated measures; U Statistic
The analysis of clustered data in a longitudinal ophthalmology study is complicated by correlations between repeatedly measured visual outcomes of paired eyes in a participant and missing observations due to the loss of follow-up. In the present article we consider hypothesis testing problems in an ophthalmology study, where eligible eyes are randomized to two treatments (when two eyes of a participant are eligible, the paired eyes are assigned to different treatments), and vision function outcomes are repeatedly measured over time. A large sample-based nonparametric test statistic and a nonparametric Bootstrap test analog are proposed for testing an interaction effect of two factors and testing an effect of a eye-specific factor within a level of the other person-specific factor on visual function outcomes. Both test statistics allow for missing observations, correlations between repeatedly measured outcomes on individual eyes, and correlations between repeatedly measured outcomes on both eyes of each participant. A simulation study shows that these proposed test statistics maintain nominal significance levels approximately and comparable powers to each other, as well as higher powers than the naive test statistic ignoring correlations between repeated bilateral measurements of both eyes in the same person. For illustration, we apply the proposed test statistics to the changes of visual field defect score in the Advanced Glaucoma Intervention Study.