Likelihood-based inferences about the mean area under a longitudinal curve in the presence of observations subject to limits of detection

Pharm Stat. 2015 May-Jun;14(3):252-61. doi: 10.1002/pst.1681. Epub 2015 Apr 1.

Abstract

Comparison of groups in longitudinal studies is often conducted using the area under the outcome versus time curve. However, outcomes may be subject to censoring due to a limit of detection and specific methods that take informative missingness into account need to be applied. In this article, we present a unified model-based method that accounts for both the within-subject variability in the estimation of the area under the curve as well as the missingness mechanism in the event of censoring. Simulation results demonstrate that our proposed method has a significant advantage over traditionally implemented methods with regards to its inferential properties. A working example from an AIDS study is presented to demonstrate the applicability of our approach.

MeSH terms

  • Area Under Curve*
  • Bias
  • Data Interpretation, Statistical*
  • Double-Blind Method
  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Likelihood Functions*
  • Limit of Detection*
  • Longitudinal Studies*
  • Models, Statistical
  • Randomized Controlled Trials as Topic / methods
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • HIV Protease Inhibitors