Improved GSimp: A Flexible Missing Value Imputation Method to Support Regulatory Bioequivalence Assessment.

Abstract

Missing values are not uncommon in in vivo bioequivalence (BE) studies and pose non-trivial challenges for BE assessment. Missing values typically appear as a mixture of different types, such as Missing Not at Random (MNAR) and Missing Completely at Random (MCAR), however, current data imputation methods were usually developed for a certain type of missing values (e.g., MNAR). Among them, an iterative Gibbs sampler-based left-censored missing value imputation approach (GSimp) was recently developed and showed superior performance over other methods in handling MNAR data. In this study, we introduce an improved GSimp ("Improved GSimp" thereafter) that offers flexibility in handling mixed types of missing data and better imputation accuracy to support BE assessment for studies with missing values. Simulations mimicking different missing value scenarios (e.g., mixture of different missing types and proportion of missing values) were conducted to compare performance of the Improved GSimp with other methods (e.g., original GSimp and half of minimal value). Normalized root mean square error (NRMSE) was used to evaluate imputation accuracy. Our results showed that the Improved GSimp always had the best accuracy in all simulated scenarios compared to other methods.