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Bayesian Approaches for Missing Not at Random Outcome Data: The Role of Identifying Restrictions.

ABSTRACT: Missing data is almost always present in real datasets, and introduces several statistical issues. One fundamental issue is that, in the absence of strong uncheckable assumptions, effects of interest are typically not nonparametrically identified. In this article, we review the generic approach of the use of identifying restrictions from a likelihood-based perspective, and provide points of contact for several recently proposed methods. An emphasis of this review is on restrictions for nonmonotone missingness, a subject that has been treated sparingly in the literature. We also present a general, fully-Bayesian, approach which is widely applicable and capable of handling a variety of identifying restrictions in a uniform manner.

SUBMITTER: Linero AR

PROVIDER: S-EPMC6936760 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Bayesian Approaches for Missing Not at Random Outcome Data: The Role of Identifying Restrictions.

Linero Antonio R AR Daniels Michael J MJ

Statistical science : a review journal of the Institute of Mathematical Statistics 20180503 2

Missing data is almost always present in real datasets, and introduces several statistical issues. One fundamental issue is that, in the absence of strong uncheckable assumptions, effects of interest are typically not nonparametrically identified. In this article, we review the generic approach of the use of identifying restrictions from a likelihood-based perspective, and provide points of contact for several recently proposed methods. An emphasis of this review is on restrictions for nonmonoto ...[more]

PMID: 31889740

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Project description:BackgroundA number of strategies have been proposed to handle missing binary outcome data (MOD) in systematic reviews. However, none of these have been evaluated empirically in a series of published systematic reviews.MethodsUsing published systematic reviews with network meta-analysis (NMA) from a wide range of health-related fields, we evaluated comparatively the most frequently described Bayesian modelling strategies for MOD in terms of log odds ratio (log OR), between-trial variance, inconsistency factor (i.e. difference between direct and indirect estimates for a comparison), surface under the cumulative ranking (SUCRA) and rankings. We extended the Bayesian random-effects NMA model to incorporate the informative missingness odds ratio (IMOR) parameter, and applied the node-splitting approach to investigate inconsistency locally. We considered both pattern-mixture and selection models, different structures for prior distribution of log IMOR, and different scenarios for MOD. To illustrate level of agreement between different strategies and scenarios, we used Bland-Altman plots.ResultsAddressing MOD using extreme scenarios and ignoring the uncertainty about the scenarios led to systematically different and more precise log ORs compared to modelling MOD under the missing at random (MAR) assumption. Hierarchical structure of log IMORs led to lower between-trial variance, especially in the case of substantial MOD. Assuming common-within-network or trial-specific log IMORs yielded similar posterior results for all NMA estimates, whereas intervention-specific structure systematically inflated uncertainty around log ORs and SUCRAs. Pattern-mixture model agreed with selection model, particularly under the trial-specific structure; however, selection model systematically reduced precision around log IMORs. Overall, different strategies and scenarios mostly had good agreement in the case of low MOD.ConclusionsAddressing MOD using extreme scenarios and/or ignoring the uncertainty about the scenarios may negatively affect NMA estimates. Modelling MOD via the IMOR parameter can ensure bias-adjusted estimates and offer valuable insights into missingness mechanisms. The researcher should seek an expert opinion in order to decide on the structure of log IMOR that best aligns to the condition and interventions studied and to define a proper prior distribution for log IMOR. Our findings also apply to pairwise meta-analyses.

Project description:The PathoLogic program constructs Pathway/Genome databases by using a genome's annotation to predict the set of metabolic pathways present in an organism. PathoLogic determines the set of reactions composing those pathways from the enzymes annotated in the organism's genome. Most annotation efforts fail to assign function to 40-60% of sequences. In addition, large numbers of sequences may have non-specific annotations (e.g., thiolase family protein). Pathway holes occur when a genome appears to lack the enzymes needed to catalyze reactions in a pathway. If a protein has not been assigned a specific function during the annotation process, any reaction catalyzed by that protein will appear as a missing enzyme or pathway hole in a Pathway/Genome database.We have developed a method that efficiently combines homology and pathway-based evidence to identify candidates for filling pathway holes in Pathway/Genome databases. Our program not only identifies potential candidate sequences for pathway holes, but combines data from multiple, heterogeneous sources to assess the likelihood that a candidate has the required function. Our algorithm emulates the manual sequence annotation process, considering not only evidence from homology searches, but also considering evidence from genomic context (i.e., is the gene part of an operon?) and functional context (e.g., are there functionally-related genes nearby in the genome?) to determine the posterior belief that a candidate has the required function. The method can be applied across an entire metabolic pathway network and is generally applicable to any pathway database. The program uses a set of sequences encoding the required activity in other genomes to identify candidate proteins in the genome of interest, and then evaluates each candidate by using a simple Bayes classifier to determine the probability that the candidate has the desired function. We achieved 71% precision at a probability threshold of 0.9 during cross-validation using known reactions in computationally-predicted pathway databases. After applying our method to 513 pathway holes in 333 pathways from three Pathway/Genome databases, we increased the number of complete pathways by 42%. We made putative assignments to 46% of the holes, including annotation of 17 sequences of previously unknown function.Our pathway hole filler can be used not only to increase the utility of Pathway/Genome databases to both experimental and computational researchers, but also to improve predictions of protein function.

Dataset Information

Bayesian Approaches for Missing Not at Random Outcome Data: The Role of Identifying Restrictions.

Publications

Bayesian Approaches for Missing Not at Random Outcome Data: The Role of Identifying Restrictions.

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