An Efficient Multiple Imputation Algorithm for Control-Based and Delta-Adjusted Pattern Mixture Models using SAS. (2nd January 2017)

• Record Type: Journal Article
• Authors: Tang, Yongqiang
• Is Part Of: Statistics in biopharmaceutical research. Volume 9:Number 1(2017)
• Page Start: 116
• Page End: 125
• Publication Date: 2017-01-02
• Subjects: Control-based imputation -- Delta-adjusted imputation -- Missing not at random -- Mixed effects model for repeated measures; Pharmacy -- Statistical methods -- Periodicals; Pharmaceutical biotechnology -- Statistical methods -- Periodicals; Biopharmaceutics -- Periodicals; Biometry -- Periodicals; Pharmacy -- Statistical methods; Periodicals; 615.190727
• DOI: 10.1080/19466315.2016.1225595
• Languages: English
• ISSNs: 1946-6315

Abstract

ABSTRACT: In clinical trials, mixed effect models for repeated measures (MMRM) and pattern mixture models (PMM) are often used to analyze longitudinal continuous outcomes. We describe a simple missing data imputation algorithm for the MMRM that can be easily implemented in standard statistical software packages such as SAS PROC MI. We explore the relationship of the missing data distribution in the control-based and delta-adjusted PMMs with that in the MMRM, and suggest an efficient imputation algorithm for these PMMs. The unobserved values in PMMs can be imputed by subtracting the mean difference in the posterior predictive distributions of missing data from the imputed values in MMRM. We also suggest a modification of the copy reference imputation procedure to avoid the possibility that after dropout, subjects from the active treatment arm will have better mean response trajectory than subjects who stay on the active treatment. The proposed methods are illustrated by the analysis of an antidepressant trial. Supplementary materials for this article are available online.