Move over LOCF: principled methods for handling missing data in sleep disorder trials

Sleep Med. 2012 Feb;13(2):123-32. doi: 10.1016/j.sleep.2011.09.007. Epub 2011 Dec 14.


Missing data, e.g. patient attrition, are endemic in sleep disorder clinical trials. Common approaches for dealing with this situation include complete-case analysis (CCA) and last observation carried forward (LOCF). Although these methods are simple to implement, they are deeply flawed in that they may introduce bias and underestimate uncertainty, leading to erroneous conclusions. There are alternative principled approaches, however, that are available in statistical software namely mixed-effects models and multiple imputation. In this paper we introduce terminology used to describe different assumptions about missing data. We emphasize that understanding reasons for missingness is a critical step in the analysis process. We describe and implement both linear mixed-effects models and an inclusive multiple imputation strategy for handling missing data in a randomized trial examining sleep outcomes. These principled strategies are compared with "complete-case analysis" and LOCF. These analyses illustrate that methodologies for accommodating missing data can produce different results in both direction and strength of treatment effects. Our goal is for this paper to serve as a guide to sleep disorder clinical trial researchers on how to utilize principled methods for incomplete data in their trial analyses.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Humans
  • Longitudinal Studies / methods*
  • Longitudinal Studies / statistics & numerical data
  • Models, Statistical*
  • Randomized Controlled Trials as Topic / methods*
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Research Design / statistics & numerical data
  • Sleep Wake Disorders / therapy*