On model selections for repeated measurement data in clinical studies

Stat Med. 2015 May 10;34(10):1621-33. doi: 10.1002/sim.6414. Epub 2015 Jan 23.

Abstract

Repeated measurement designs have been widely used in various randomized controlled trials for evaluating long-term intervention efficacies. For some clinical trials, the primary research question is how to compare two treatments at a fixed time, using a t-test. Although simple, robust, and convenient, this type of analysis fails to utilize a large amount of collected information. Alternatively, the mixed-effects model is commonly used for repeated measurement data. It models all available data jointly and allows explicit assessment of the overall treatment effects across the entire time spectrum. In this paper, we propose an analytic strategy for longitudinal clinical trial data where the mixed-effects model is coupled with a model selection scheme. The proposed test statistics not only make full use of all available data but also utilize the information from the optimal model deemed for the data. The performance of the proposed method under various setups, including different data missing mechanisms, is evaluated via extensive Monte Carlo simulations. Our numerical results demonstrate that the proposed analytic procedure is more powerful than the t-test when the primary interest is to test for the treatment effect at the last time point. Simulations also reveal that the proposed method outperforms the usual mixed-effects model for testing the overall treatment effects across time. In addition, the proposed framework is more robust and flexible in dealing with missing data compared with several competing methods. The utility of the proposed method is demonstrated by analyzing a clinical trial on the cognitive effect of testosterone in geriatric men with low baseline testosterone levels.

Keywords: bootstrap; missing data; mixed-effects model; model selection; repeated measurement; t-test.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Analysis of Variance
  • Androgens / pharmacology
  • Bias
  • Cognition / drug effects
  • Computer Simulation
  • Data Interpretation, Statistical
  • Humans
  • Longitudinal Studies
  • Male
  • Models, Statistical*
  • Randomized Controlled Trials as Topic / methods
  • Randomized Controlled Trials as Topic / standards
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Research Design / standards
  • Research Design / statistics & numerical data*
  • Testosterone / pharmacology

Substances

  • Androgens
  • Testosterone