Accounting for missing data in statistical analyses: multiple imputation is not always the answer.
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ABSTRACT:
SUBMITTER: Hughes RA
PROVIDER: S-EPMC6693809 | biostudies-other | 2019 Mar
REPOSITORIES: biostudies-other
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Project description:Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation, also called chained equations multiple imputation. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. This approach, however, assumes that the missingness mechanism is missing at random, and it is not well-justified under not-at-random missingness without additional modification. In this paper, we describe how we can generalize the sequential regression multiple imputation imputation procedure to handle missingness not at random in the setting where missingness may depend on other variables that are also missing but not on the missing variable itself, conditioning on fully observed variables. We provide algebraic justification for several generalizations of standard sequential regression multiple imputation using Taylor series and other approximations of the target imputation distribution under missingness not at random. Resulting regression model approximations include indicators for missingness, interactions, or other functions of the missingness not at random missingness model and observed data. In a simulation study, we demonstrate that the proposed sequential regression multiple imputation modifications result in reduced bias in the final analysis compared to standard sequential regression multiple imputation, with an approximation strategy involving inclusion of an offset in the imputation model performing the best overall. The method is illustrated in a breast cancer study, where the goal is to estimate the prevalence of a specific genetic pathogenic variant.
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Project description:Missing data are a common issue in cost-effectiveness analysis (CEA) alongside randomised trials and are often addressed assuming the data are 'missing at random'. However, this assumption is often questionable, and sensitivity analyses are required to assess the implications of departures from missing at random. Reference-based multiple imputation provides an attractive approach for conducting such sensitivity analyses, because missing data assumptions are framed in an intuitive way by making reference to other trial arms. For example, a plausible not at random mechanism in a placebo-controlled trial would be to assume that participants in the experimental arm who dropped out stop taking their treatment and have similar outcomes to those in the placebo arm. Drawing on the increasing use of this approach in other areas, this paper aims to extend and illustrate the reference-based multiple imputation approach in CEA. It introduces the principles of reference-based imputation and proposes an extension to the CEA context. The method is illustrated in the CEA of the CoBalT trial evaluating cognitive behavioural therapy for treatment-resistant depression. Stata code is provided. We find that reference-based multiple imputation provides a relevant and accessible framework for assessing the robustness of CEA conclusions to different missing data assumptions.
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Project description:BackgroundIncomplete categorical variables with more than two categories are common in public health data. However, most of the existing missing-data methods do not use the information from nonresponse (missingness) probabilities.MethodsWe propose a nearest-neighbour multiple imputation approach to impute a missing at random categorical outcome and to estimate the proportion of each category. The donor set for imputation is formed by measuring distances between each missing value with other non-missing values. The distance function is calculated based on a predictive score, which is derived from two working models: one fits a multinomial logistic regression for predicting the missing categorical outcome (the outcome model) and the other fits a logistic regression for predicting missingness probabilities (the missingness model). A weighting scheme is used to accommodate contributions from two working models when generating the predictive score. A missing value is imputed by randomly selecting one of the non-missing values with the smallest distances. We conduct a simulation to evaluate the performance of the proposed method and compare it with several alternative methods. A real-data application is also presented.ResultsThe simulation study suggests that the proposed method performs well when missingness probabilities are not extreme under some misspecifications of the working models. However, the calibration estimator, which is also based on two working models, can be highly unstable when missingness probabilities for some observations are extremely high. In this scenario, the proposed method produces more stable and better estimates. In addition, proper weights need to be chosen to balance the contributions from the two working models and achieve optimal results for the proposed method.ConclusionsWe conclude that the proposed multiple imputation method is a reasonable approach to dealing with missing categorical outcome data with more than two levels for assessing the distribution of the outcome. In terms of the choices for the working models, we suggest a multinomial logistic regression for predicting the missing outcome and a binary logistic regression for predicting the missingness probability.
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