Graduation Year


Document Type




Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Epidemiology and Biostatistics

Major Professor

Yougui Wu, Ph.D.

Committee Member

Getachew A. Dagne, Ph.D.

Committee Member

Yangxin Huang, Ph.D.

Committee Member

Paul Leaverton, Ph.D.


unbalanced design, balanced design, interval censor, time to event


In longitudinal studies, the exact timing of an event often cannot be observed, and is usually detected at a subsequent visit, which is called interval censoring. Spacing of the visits is important when designing study with interval censored data. In a typical longitudinal study, the spacing of visits is usually the same across all subjects (balanced design). In this dissertation, I propose an unbalanced design: subjects at baseline are divided into a high risk group and a low risk group based on a risk factor, and the subjects in the high risk group are followed more frequently than those in the low risk group. Using a simple setting of a single binary exposure of interest (covariate) and exponentially distributed survival times, I derive the explicit formula for the asymptotic sampling variance of the estimate for the covariate effect. It shows that the asymptotic sampling variance can be simply reduced by increasing the number of examinations in the high risk group. The relative reduction tends to be greater when the baseline hazard rate in the high risk group is much higher than that in the low risk group and tends to be larger when the frequency of assessments in the low risk group is relatively sparse. Numeric simulations are also used to verify the asymptotic results in small samples and evaluate the efficiency of the unbalanced design in more complicated settings. Beyond comparing the asymptotic sampling variances, I further evaluate the power and empirical Type I error from unbalanced design and compare against the traditional balanced design. Data from a randomized clinical trial for type 1 diabetes are further used to test the performance of the proposed unbalanced design, and the parametric analyses of these data confirmed the findings from the theoretical and numerical studies.

Included in

Biostatistics Commons