Guideline on missing data in confirmatory clinical trials

Abstract

Missing data is an unavoidable problem in the research of confirmatory clinical trials,and the approach for handling missing data is an important factor affecting the objectivity of the trial conclusions.The data missing in the clinical trial is mainly induced by drop-out,which could be classified as missing completely at random(MCAR),missing at random(MAR) and missing not at random(MNAR) according to the mechanism.The bias of trial conclusion could be reduced through the complete case analysis,careful selection of the method handling for missing data(e.g.,imputation and mixed models) and the sensitivity analysis.To address this issue,European Medicines Evaluation Agency(EMEA) published a guideline on the missing data in the confirmatory clinical trial,and now it had come into effect.With focus on this guideline,we presented the main methods for handling missing data in clinical trials in this paper with the aim providing information for the drug development and clinical research in China.