Longitudinal Trials with Adaptive Choice of Follow-Up Time

• Activity Number: 175
• Type: Contributed
• Date/Time: Monday, August 5, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Neal Jeffries*+ and Nancy L. Geller
• Companies: National Heart, Lung, and Blood Institute,-NIH and Office of Biostatistics Research, NHLBI, NIH
• Keywords: adaptive design ; longitudinal clinical trials ; group sequential analysis

Abstract

In longitudinal studies comparing two or more treatments with a maximum follow-up time there may be interest in examining treatment effects for intermediate follow-up times. One motivation may be to identify the time period with greatest treatment difference when there is a non-monotone treatment effect over time; another motivation may be to make the trial more efficient in terms of time to reach a decision on whether a new treatment is efficacious or not. Suppose the test statistic Zti will be used to test the hypothesis of no treatment effect at a fixed time ti. In this context a common approach is to perform a pilot study on n1 subjects, and evaluate the treatment effect at the fixed time points ti and choose t* as the value of ti for which Zti is maximized. Having chosen t* a second trial can be designed. We consider several adaptive alternatives to this approach that treat the pilot and second trial as a seamless, combined entity and evaluate type I error and power characteristics. The adaptive designs we consider typically have improved power over the common, separate trial approach.