In clinical trials, mixed effects 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.
This article focuses on measurement error in covariates in regression analyses in which the aim is to estimate the association between one or more covariates and an outcome, adjusting for confounding. Error in covariate measurements, if ignored, results in biased estimates of parameters representing the associations of interest. Studies with variables measured with error can be considered as studies in which the true variable is missing, for either some or all study participants. We make the link between measurement error and missing data and describe methods for correcting for bias due to cov…
tBayes-MICE: A Bayesian Approach to Multiple Imputation for Time Series Data
Transitional Artificial Intelligence Research Group, School of Mathematics and Statistics, UNSW, Sydney, Australia（过渡人工智能研究组，数学与统计学院，新南威尔士大学，悉尼，澳大利亚）；School of Mathematics and Statistics, UNSW, Sydney, Australia（数学与统计学院，新南威尔士大学，悉尼，澳大利亚）
A method using multiple imputation and bootstrap for dealing with missing data in mediation analysis is introduced and implemented in SAS. Through simulation studies, it is shown that the method performs well for both MCAR and MAR data without and with auxiliary variables. It is also shown that the method works equally well for MNAR data if auxiliary variables related to missingness are included. The application of the method is demonstrated through the analysis of a subset of data from the National Longitudinal Survey of Youth.
Censored survival data are common in clinical trial studies. We propose a unified framework for sensitivity analysis to censoring at random in survival data using multiple imputation and martingale, called SMIM. The proposed framework adopts the δ-adjusted and control-based models, indexed by the sensitivity parameter, entailing censoring at random and a wide collection of censoring not at random assumptions. Also, it targets for a broad class of treatment effect estimands defined as functionals of treatment-specific survival functions, taking into account of missing data due to censoring. Mul…
Adjusting for Outcome Reporting Bias in Meta-analysis: A Multiple Imputation Approach
Epidemiology, Biostatistics and Prevention Institute (EBPI)（流行病学、生物统计学与预防研究所）；Center for Reproducible Science and Research Synthesis (CRS)（可重复科学与研究综合中心）；University of Zurich (UZH)（苏黎世大学）
Recent advances in computational methods for intractable models have made network data increasingly amenable to statistical analysis. Exponential random graph models (ERGMs) emerged as one of the main families of models capable of capturing the complex dependence structure of network data in a wide range of applied contexts. The Bergm package for R has become a popular package to carry out Bayesian parameter inference, missing data imputation, model selection and goodness-of-fit diagnostics for ERGMs. Over the last few years, the package has been considerably improved in terms of efficiency by…
Risk modeling with EHR data is challenging due to a lack of direct observations on the disease outcome, and the high dimensionality of the candidate predictors. In this paper, we develop a surrogate assisted semi-supervised-learning (SAS) approach to risk modeling with high dimensional predictors, leveraging a large unlabeled data on candidate predictors and surrogates of outcome, as well as a small labeled data with annotated outcomes. The SAS procedure borrows information from surrogates along with candidate predictors to impute the unobserved outcomes via a sparse working imputation model w…
Population adjustment methods such as matching-adjusted indirect comparison (MAIC) are increasingly used to compare marginal treatment effects when there are cross-trial differences in effect modifiers and limited patient-level data. MAIC is sensitive to poor covariate overlap and cannot extrapolate beyond the observed covariate space. Current outcome regression-based alternatives can extrapolate but target a conditional treatment effect that is incompatible in the indirect comparison. When adjusting for covariates, one must integrate or average the conditional estimate over the population of …
The mixed effects model for repeated measures (MMRM) has been widely used for the analysis of longitudinal clinical data collected at a number of fixed time points. We propose a robust extension of the MMRM for skewed and heavy-tailed data on basis of the multivariate skew-t distribution, and it includes the multivariate normal, t, and skew-normal distributions as special cases. An efficient Markov chain Monte Carlo algorithm is developed using the monotone data augmentation and parameter expansion techniques. We employ the algorithm to perform controlled pattern imputations for sensitivity an…
Attrition is a common occurrence in cluster randomised trials (CRTs) which leads to missing outcome data. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. This paper compares the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis and linear mixed model (LMM) analysis, under baseline covariate dependent missingness (CDM) in continuous outcomes, in terms of bias, average estimated standard error and coverage probability. The methods of complete case analysis (CCA) and multiple imputation (MI) are …
Missing outcomes are a commonly occurring problem for cluster randomised trials, which can lead to biased and inefficient inference if ignored or handled inappropriately. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. In this study, we assessed the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis, random effects logistic regression (RELR) and generalised estimating equations (GEE) when binary outcomes are missing under a baseline covariate dependent missingness mechanism. Missing outcomes we…
