Evolution of Protein Molecules

25. Multiple Imputation for Nonresponse in Surveys. By D. B. Rubin. ISBN 0 471 08705 X. Wiley, Chichester, 1987. 258 pp. £30.25.

Multiple Imputation for Nonresponse in Surveys

We investigate conditions sufficient for identification of average treatment effects using instrumental variables. First we show that the existence of valid instruments is not sufficient to identify any meaningful average treatment effect. We then establish that the combination of an instrument and a condition on the relation between the instrument and the participation status is sufficient for identification of a local average treatment effect for those who can be induced to change their participation status by changing the value of the instrument. Finally we derive the probability limit of the standard IV estimator under these conditions. It is seen to be a weighted average of local average treatment effects.

Evolution and Rationality Some Recent Game-Theoretic Results. Identification and Estimation of Local Average Treatment Effects

Virtually all discussions and applications of statistical mediation analysis have been based on the condition that the independent variable is dichotomous or continuous, even though investigators frequently are interested in testing mediation hypotheses involving a multicategorical independent variable (such as two or more experimental conditions relative to a control group). We provide a tutorial illustrating an approach to estimation of and inference about direct, indirect, and total effects in statistical mediation analysis with a multicategorical independent variable. The approach is mathematically equivalent to analysis of (co)variance and reproduces the observed and adjusted group means while also generating effects having simple interpretations. Supplementary material available online includes extensions to this approach and Mplus, SPSS, and SAS code that implements it.

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Statistical mediation analysis with a multicategorical independent variable

Omnibus Tests of the Indirect Effect in Statistical Mediation Analysis with a Multicategorical Independent Variable

For dichotomous outcomes, the authors discuss when the standard approaches to mediation analysis used in epidemiology and the social sciences are valid, and they provide alternative mediation analysis techniques when the standard approaches will not work. They extend definitions of controlled direct effects and natural direct and indirect effects from the risk difference scale to the odds ratio scale. A simple technique to estimate direct and indirect effect odds ratios by combining logistic and linear regressions is described that applies when the outcome is rare and the mediator continuous. Further discussion is given as to how this mediation analysis technique can be extended to settings in which data come from a case-control study design. For the standard mediation analysis techniques used in the epidemiologic and social science literatures to be valid, an assumption of no interaction between the effects of the exposure and the mediator on the outcome is needed. The approach presented here, however, will apply even when there are interactions between the effect of the exposure and the mediator on the outcome.

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Odds Ratios for Mediation Analysis for a Dichotomous Outcome

Concepts concerning mediation in the causal inference literature are reviewed. Notions of direct and indirect effects from a counterfactual approach to mediation are compared with those arising from the standard regression approach to mediation of Baron and Kenny (1986), commonly utilized in the social science literature. It is shown that concepts of direct and indirect effect from causal inference generalize those described by Baron and Kenny and that under appropriate identification assumptions these more general direct and indirect effects from causal inference can be estimated using regression even when there are interactions between the primary exposure of interest and the mediator. A number of conceptual issues are discussed concerning the interpretation of identification conditions for mediation, the notion of counterfactuals based on hypothetical interventions and the so called consistency and composition assumptions.

https://www.intlpress.com/site/pub/files/_fulltext/journals/sii/2009/0002/0004/SII-2009-0002-0004-a007.pdf

Conceptual issues concerning mediation, interventions and composition

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

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Mediation Analysis with Multiple Mediators

Rationale: Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results.Objectives: We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference.Methods: Patients (n = 4,479) from the longitudinal prospective (1997–2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity.Measurements and Main Results: Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval,...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.201105-0867OC

Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.

An important problem within both epidemiology and many social sciences is to break down the effect of a given treatment into different causal pathways and to quantify the importance of each pathway. Formal mediation analysis based on counterfactuals is a key tool when addressing this problem. During the last decade, the theoretical framework for mediation analysis has been greatly extended to enable the use of arbitrary statistical models for outcome and mediator. However, the researcher attempting to use these techniques in practice will often find implementation a daunting task, as it tends to require special statistical programming. In this paper, the authors introduce a simple procedure based on marginal structural models that directly parameterize the natural direct and indirect effects of interest. It tends to produce more parsimonious results than current techniques, greatly simplifies testing for the presence of a direct or an indirect effect, and has the advantage that it can be conducted in standard software. However, its simplicity comes at the price of relying on correct specification of models for the distribution of mediator (and exposure) and accepting some loss of precision compared with more complex methods. Web Appendixes 1 and 2, which are posted on the Journal's Web site (http://aje.oupjournals.org/), contain implementation examples in SAS software (SAS Institute, Inc., Cary, North Carolina) and R language (R Foundation for Statistical Computing, Vienna, Austria).

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Stijn Vansteelandt

Papers

Odds Ratios for Mediation Analysis for a Dichotomous Outcome

Conceptual issues concerning mediation, interventions and composition

Mediation Analysis with Multiple Mediators

Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.

A Simple Unified Approach for Estimating Natural Direct and Indirect Effects