Missing data in clinical studies: issues and methods.

Missing data are a prevailing problem in any type of data analyses. A participant variable is considered missing if the value of the variable (outcome or covariate) for the participant is not observed. In this article, various issues in analyzing studies with missing data are discussed. Particularly, we focus on missing response and/or covariate data for studies with discrete, continuous, or time-to-event end points in which generalized linear models, models for longitudinal data such as generalized linear mixed effects models, or Cox regression models are used. We discuss various classifications of missing data that may arise in a study and demonstrate in several situations that the commonly used method of throwing out all participants with any missing data may lead to incorrect results and conclusions. The methods described are applied to data from an Eastern Cooperative Oncology Group phase II clinical trial of liver cancer and a phase III clinical trial of advanced non-small-cell lung cancer. Although the main area of application discussed here is cancer, the issues and methods we discuss apply to any type of study.