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Full-Text Articles in Physical Sciences and Mathematics

Robust Inference On Effects Attributable To Mediators: A Controlled-Direct-Effect-Based Approach For Causal Effect Decomposition With Multiple Mediators, An-Shun Tai, Yi-Juan Du, Sheng-Hsuan Lin Aug 2020

Robust Inference On Effects Attributable To Mediators: A Controlled-Direct-Effect-Based Approach For Causal Effect Decomposition With Multiple Mediators, An-Shun Tai, Yi-Juan Du, Sheng-Hsuan Lin

Harvard University Biostatistics Working Paper Series

Effect decomposition is a critical technique for mechanism investigation in settings with multiple causally ordered mediators. Causal mediation analysis is a standard method for effect decomposition, but the assumptions required for the identification process are extremely strong. By extending the framework of controlled direct effects, this study proposes the effect attributable to mediators (EAM) as a novel measure for effect decomposition. For policy making, EAM represents how much an effect can be eliminated by setting mediators to certain values. From the perspective of mechanism investigation, EAM contains information about how much a particular mediator or set of mediators is involved …


Integrated Multiple Mediation Analysis: A Robustness–Specificity Trade-Off In Causal Structure, An-Shun Tai, Sheng-Hsuan Lin May 2020

Integrated Multiple Mediation Analysis: A Robustness–Specificity Trade-Off In Causal Structure, An-Shun Tai, Sheng-Hsuan Lin

Harvard University Biostatistics Working Paper Series

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and …


Survival Mediation Analysis With The Death-Truncated Mediator: The Completeness Of The Survival Mediation Parameter, An-Shun Tai, Chun-An Tsai, Sheng-Hsuan Lin Apr 2020

Survival Mediation Analysis With The Death-Truncated Mediator: The Completeness Of The Survival Mediation Parameter, An-Shun Tai, Chun-An Tsai, Sheng-Hsuan Lin

Harvard University Biostatistics Working Paper Series

In medical research, the development of mediation analysis with a survival outcome has facilitated investigation into causal mechanisms. However, studies have not discussed the death-truncation problem for mediators, the problem being that conventional mediation parameters cannot be well-defined in the presence of a truncated mediator. In the present study, we systematically defined the completeness of causal effects to uncover the gap, in conventional causal definitions, between the survival and nonsurvival settings. We proposed three approaches to redefining the natural direct and indirect effects, which are generalized forms of the conventional causal effects for survival outcomes. Furthermore, we developed three statistical …


Estimating Marginal Hazard Ratios By Simultaneously Using A Set Of Propensity Score Models: A Multiply Robust Approach, Di Shu, Peisong Han, Rui Wang, Sengwee Toh Jan 2020

Estimating Marginal Hazard Ratios By Simultaneously Using A Set Of Propensity Score Models: A Multiply Robust Approach, Di Shu, Peisong Han, Rui Wang, Sengwee Toh

Harvard University Biostatistics Working Paper Series

The inverse probability weighted Cox model is frequently used to estimate marginal hazard ratios. Its validity requires a crucial condition that the propensity score model is correctly specified. To provide protection against misspecification of the propensity score model, we propose a weighted estimation method rooted in empirical likelihood theory. The proposed estimator is multiply robust in that it is guaranteed to be consistent when a set of postulated propensity score models contains a correctly specified model. Our simulation studies demonstrate satisfactory finite sample performance of the proposed method in terms of consistency and efficiency. We apply the proposed method to …


Estimation Of Conditional Power For Cluster-Randomized Trials With Interval-Censored Endpoints, Kaitlyn Cook, Rui Wang Jan 2020

Estimation Of Conditional Power For Cluster-Randomized Trials With Interval-Censored Endpoints, Kaitlyn Cook, Rui Wang

Harvard University Biostatistics Working Paper Series

Cluster-randomized trials (CRTs) of infectious disease preventions often yield correlated, interval-censored data: dependencies may exist between observations from the same cluster, and event occurrence may be assessed only at intermittent clinic visits. This data structure must be accounted for when conducting interim monitoring and futility assessment for CRTs. In this article, we propose a flexible framework for conditional power estimation when outcomes are correlated and interval-censored. Under the assumption that the survival times follow a shared frailty model, we first characterize the correspondence between the marginal and cluster-conditional survival functions, and then use this relationship to semiparametrically estimate the cluster-specific …


Randomization-Based Confidence Intervals For Cluster Randomized Trials, Dustin J. Rabideau, Rui Wang Jan 2020

Randomization-Based Confidence Intervals For Cluster Randomized Trials, Dustin J. Rabideau, Rui Wang

Harvard University Biostatistics Working Paper Series

In a cluster randomized trial (CRT), groups of people are randomly assigned to different interventions. Existing parametric and semiparametric methods for CRTs rely on distributional assumptions or a large number of clusters to maintain nominal confidence interval (CI) coverage. Randomization-based inference is an alternative approach that is distribution-free and does not require a large number of clusters to be valid. Although it is well-known that a CI can be obtained by inverting a randomization test, this requires randomization testing a non-zero null hypothesis, which is challenging with non-continuous and survival outcomes. In this paper, we propose a general method for …


Power Calculation For Cross-Sectional Stepped-Wedge Cluster Randomized Trials With Binary Outcomes, Linda J. Harrison, Rui Wang Jan 2020

Power Calculation For Cross-Sectional Stepped-Wedge Cluster Randomized Trials With Binary Outcomes, Linda J. Harrison, Rui Wang

Harvard University Biostatistics Working Paper Series

Power calculation for stepped-wedge cluster randomized trials (SW-CRTs) presents unique challenges, beyond those of standard cluster randomized trials (CRTs), due to the need to consider temporal within cluster correlations and background period effects. To date, power calculation methods specific to SW-CRTs have primarily been developed under a linear model. When the outcome is binary, the use of a linear model corresponds to assessing a prevalence difference; yet trial analysis often employs a non-linear link function. We assess power for cross-sectional SW-CRTs under a logistic model fitted by generalized estimating equations. Firstly, under an exchangeable correlation structure, we show the power …