Interim Futility Analysis based on Linear Regression with Longitudinal Endpoint in A Rare Disease Indication
*GQ Cai, GSK 


There are many clinical trials where the primary endpoint is observed at a specific long-term follow-up time, while repeated measures of the same outcome are also taken at earlier visits. In such cases, it is possible that interim futility analyses will be planned such that the trials can be terminated early if the treatment does not induce any benefit to the patients. For such trials subjects only provide data on the primary endpoint once they have completed the long-term follow-up time, potentially eliminating a large proportion of the enrolled subjects from an interim analysis. We propose a more efficient interim analysis based on the slope of a linear regression, which incorporates all the data available at the interim analysis. This approach has the added advantage of providing a data-drive decision about the timing of the interim. The construction of interim futility rules and the timing of the interim analysis are discussed and the method is illustrated with an example involving a placebo-controlled comparison of longitudinal proteinuria measurements in a rare renal disease.