Sample size calculations for time-averaged difference of longitudinal binary outcomes

• Published in: Communications in statistics. Theory and methods Vol. 46; no. 1; pp. 344 - 353
• Main Authors: Lou, Ying, Cao, Jing, Zhang, Song, Ahn, Chul
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.01.2017; Taylor & Francis Ltd
• Subjects: 92B15 (General Biostatistics); Binary; Clinical trials; Design parameters; GEE; Mathematical analysis; Medical research; Mixture of missing patterns; Repeated measurements; Sample size; Samples; Statistical analysis; Statistical methods; Statistics; Time measurement; Time-averaged differences; sample size; GEE; mixture of missing patterns; time-averaged differences; binary; repeated measurements
• ISSN: 0361-0926; 1532-415X
• DOI: 10.1080/03610926.2014.991040

In clinical trials with repeated measurements, the responses from each subject are measured multiple times during the study period. Two approaches have been widely used to assess the treatment effect, one that compares the rate of change between two groups and the other that tests the time-averaged difference (TAD). While sample size calculations based on comparing the rate of change between two groups have been reported by many investigators, the literature has paid relatively little attention to the sample size estimation for time-averaged difference (TAD) in the presence of heterogeneous correlation structure and missing data in repeated measurement studies. In this study, we investigate sample size calculation for the comparison of time-averaged responses between treatment groups in clinical trials with longitudinally observed binary outcomes. The generalized estimating equation (GEE) approach is used to derive a closed-form sample size formula, which is flexible enough to account for arbitrary missing patterns and correlation structures. In particular, we demonstrate that the proposed sample size can accommodate a mixture of missing patterns, which is frequently encountered by practitioners in clinical trials. To our knowledge, this is the first study that considers the mixture of missing patterns in sample size calculation. Our simulation shows that the nominal power and type I error are well preserved over a wide range of design parameters. Sample size calculation is illustrated through an example.