59,776 research outputs found
Causal Inference in Longitudinal Studies with History-Restricted Marginal Structural Models
Causal Inference based on Marginal Structural Models (MSMs) is particularly attractive to subject-matter investigators because MSM parameters provide explicit representations of causal effects. We introduce History-Restricted Marginal Structural Models (HRMSMs) for longitudinal data for the purpose of defining causal parameters which may often be better suited for Public Health research. This new class of MSMs allows investigators to analyze the causal effect of a treatment on an outcome based on a fixed, shorter and user-specified history of exposure compared to MSMs. By default, the latter represents the treatment causal effect of interest based on a treatment history defined by the treatments assigned between the study\u27s start and outcome collection. Beyond allowing a more flexible causal analysis, the proposed HRMSMs also mitigate computing issues related to MSMs as well as statistical power concerns when designing longitudinal studies. We develop three consistent estimators of HRMSM parameters under sufficient model assumptions: the Inverse Probability of Treatment Weighted (IPTW), G-computation and Double Robust (DR) estimators. In addition, we show that the assumptions commonly adopted for identification and consistent estimation of MSM parameters (existence of counterfactuals, consistency, time-ordering and sequential randomization assumptions) also lead to identification and consistent estimation of HRMSM parameters
Counting and Sampling from Markov Equivalent DAGs Using Clique Trees
A directed acyclic graph (DAG) is the most common graphical model for
representing causal relationships among a set of variables. When restricted to
using only observational data, the structure of the ground truth DAG is
identifiable only up to Markov equivalence, based on conditional independence
relations among the variables. Therefore, the number of DAGs equivalent to the
ground truth DAG is an indicator of the causal complexity of the underlying
structure--roughly speaking, it shows how many interventions or how much
additional information is further needed to recover the underlying DAG. In this
paper, we propose a new technique for counting the number of DAGs in a Markov
equivalence class. Our approach is based on the clique tree representation of
chordal graphs. We show that in the case of bounded degree graphs, the proposed
algorithm is polynomial time. We further demonstrate that this technique can be
utilized for uniform sampling from a Markov equivalence class, which provides a
stochastic way to enumerate DAGs in the equivalence class and may be needed for
finding the best DAG or for causal inference given the equivalence class as
input. We also extend our counting and sampling method to the case where prior
knowledge about the underlying DAG is available, and present applications of
this extension in causal experiment design and estimating the causal effect of
joint interventions
A new approach to hierarchical data analysis: Targeted maximum likelihood estimation for the causal effect of a cluster-level exposure
We often seek to estimate the impact of an exposure naturally occurring or
randomly assigned at the cluster-level. For example, the literature on
neighborhood determinants of health continues to grow. Likewise, community
randomized trials are applied to learn about real-world implementation,
sustainability, and population effects of interventions with proven
individual-level efficacy. In these settings, individual-level outcomes are
correlated due to shared cluster-level factors, including the exposure, as well
as social or biological interactions between individuals. To flexibly and
efficiently estimate the effect of a cluster-level exposure, we present two
targeted maximum likelihood estimators (TMLEs). The first TMLE is developed
under a non-parametric causal model, which allows for arbitrary interactions
between individuals within a cluster. These interactions include direct
transmission of the outcome (i.e. contagion) and influence of one individual's
covariates on another's outcome (i.e. covariate interference). The second TMLE
is developed under a causal sub-model assuming the cluster-level and
individual-specific covariates are sufficient to control for confounding.
Simulations compare the alternative estimators and illustrate the potential
gains from pairing individual-level risk factors and outcomes during
estimation, while avoiding unwarranted assumptions. Our results suggest that
estimation under the sub-model can result in bias and misleading inference in
an observational setting. Incorporating working assumptions during estimation
is more robust than assuming they hold in the underlying causal model. We
illustrate our approach with an application to HIV prevention and treatment
Bayesian hierarchical modeling for signaling pathway inference from single cell interventional data
Recent technological advances have made it possible to simultaneously measure
multiple protein activities at the single cell level. With such data collected
under different stimulatory or inhibitory conditions, it is possible to infer
the causal relationships among proteins from single cell interventional data.
In this article we propose a Bayesian hierarchical modeling framework to infer
the signaling pathway based on the posterior distributions of parameters in the
model. Under this framework, we consider network sparsity and model the
existence of an association between two proteins both at the overall level
across all experiments and at each individual experimental level. This allows
us to infer the pairs of proteins that are associated with each other and their
causal relationships. We also explicitly consider both intrinsic noise and
measurement error. Markov chain Monte Carlo is implemented for statistical
inference. We demonstrate that this hierarchical modeling can effectively pool
information from different interventional experiments through simulation
studies and real data analysis.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS425 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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