Causal Estimation with Functional Confounders.
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ABSTRACT:
SUBMITTER: Puli A
PROVIDER: S-EPMC8096536 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundStandard regression modeling may cause biased effect estimates in the presence of time-varying confounders affected by prior exposure. This study aimed to quantify the relationship between declining in modified creatinine index (MCI), as a surrogate marker of lean body mass, and mortality among end stage renal disease (ESRD) patients using G-estimation accounting appropriately for time-varying confounders.MethodsA retrospective cohort of all registered ESRD patients (n = 553) was constructed over 8 years from 2011 to 2019, from 3 hemodialysis centers at Kerman, southeast of Iran. According to changes in MCI, patients were dichotomized to either the decline group or no-decline group. Subsequently the effect of interest was estimated using G-estimation and compared with accelerated failure time (AFT) Weibull models using two modelling strategies.ResultsStandard models demonstrated survival time ratios of 0.91 (95% confidence interval [95% CI]: 0.64 to 1.28) and 0.84 (95% CI: 0.58 to 1.23) in patients in the decline MCI group compared to those in no-decline MCI group. This effect was demonstrated to be 0.57 (-95% CI: 0.21 to 0.81) using G-estimation.ConclusionDeclining in MCI increases mortality in patients with ESRD using G-estimation, while the AFT standard models yield biased effect estimate toward the null.
| S-EPMC9390931 | biostudies-literature
Project description:Mapping gene expression as a quantitative trait using whole genome-sequencing and transcriptome analysis allows to discover the functional consequences of genetic variation. We developed a novel method and ultra-fast software Findr for higly accurate causal inference between gene expression traits using cis-regulatory DNA variations as causal anchors, which improves current methods by taking into consideration hidden confounders and weak regulations. Findr outperformed existing methods on the DREAM5 Systems Genetics challenge and on the prediction of microRNA and transcription factor targets in human lymphoblastoid cells, while being nearly a million times faster. Findr is publicly available at https://github.com/lingfeiwang/findr.
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Project description:Doubly robust estimation combines a form of outcome regression with a model for the exposure (i.e., the propensity score) to estimate the causal effect of an exposure on an outcome. When used individually to estimate a causal effect, both outcome regression and propensity score methods are unbiased only if the statistical model is correctly specified. The doubly robust estimator combines these 2 approaches such that only 1 of the 2 models need be correctly specified to obtain an unbiased effect estimator. In this introduction to doubly robust estimators, the authors present a conceptual overview of doubly robust estimation, a simple worked example, results from a simulation study examining performance of estimated and bootstrapped standard errors, and a discussion of the potential advantages and limitations of this method. The supplementary material for this paper, which is posted on the Journal's Web site (http://aje.oupjournals.org/), includes a demonstration of the doubly robust property (Web Appendix 1) and a description of a SAS macro (SAS Institute, Inc., Cary, North Carolina) for doubly robust estimation, available for download at http://www.unc.edu/~mfunk/dr/.
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Project description:A large body of research shows that the Central Nervous System (CNS) integrates multisensory information. However, this strategy should only apply to multisensory signals that have a common cause; independent signals should be segregated. Causal Inference (CI) models account for this notion. Surprisingly, previous findings suggested that visual and inertial cues on heading of self-motion are integrated regardless of discrepancy. We hypothesized that CI does occur, but that characteristics of the motion profiles affect multisensory processing. Participants estimated heading of visual-inertial motion stimuli with several different motion profiles and a range of intersensory discrepancies. The results support the hypothesis that judgments of signal causality are included in the heading estimation process. Moreover, the data suggest a decreasing tolerance for discrepancies and an increasing reliance on visual cues for longer duration motions.
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Project description:BackgroundCausal inference has seen an increasing popularity in medical research. Estimation of causal effects from observational data allows to draw conclusions from data when randomized controlled trials cannot be conducted. Although the identification of structural causal models (SCM) and the calculation of structural coefficients has received much attention, a key requirement for valid causal inference is that conclusions are drawn based on the true data-generating model.MethodsIt remains widely unknown how large the probability is to reject the true structural causal model when observational data from it is sampled. The latter probability - the causal false-positive risk - is crucial, as rejection of the true causal model can induce bias in the estimation of causal effects. In this paper, the widely used causal models of confounders and colliders are studied regarding their causal false-positive risk in linear Markovian models. A simulation study is carried out which investigates the causal false-positive risk in Gaussian linear Markovian models. Therefore, the testable implications of the DAG corresponding to confounders and colliders are analyzed from a Bayesian perspective. Furthermore, the induced bias in estimating the structural coefficients and causal effects is studied.ResultsResults show that the false-positive risk of rejecting a true SCM of even simple building blocks like confounders and colliders is substantial. Importantly, estimation of average, direct and indirect causal effects can become strongly biased if a true model is rejected. The causal false-positive risk may thus serve as an indicator or proxy for the induced bias.ConclusionWhile the identification of structural coefficients and testable implications of causal models have been studied rigorously in the literature, this paper shows that causal inference also must develop new concepts for controlling the causal false-positive risk. Although a high risk cannot be equated with a substantial bias, it is indicative of the induced bias. The latter fact calls for the development of more advanced risk measures for committing a causal type I error in causal inference.
| S-EPMC8883695 | biostudies-literature
Project description:BackgroundProbabilistic bias and Bayesian analyses are important tools for bias correction, particularly when required parameters are nonidentifiable. Negative controls are another tool; they can be used to detect and correct for confounding. Our goals are to present conditions that assure identifiability of certain causal effects and to describe and illustrate a probabilistic bias analysis and related Bayesian analysis that use a negative control exposure.MethodsUsing potential-outcome models, we characterized assumptions needed for identification of causal effects using a dichotomous, negative control exposure when residual confounding exists. We defined bias parameters, characterized their relationships with the negative control and with specified causal effects, and described the corresponding probabilistic-bias and Bayesian analyses. We present analytic examples using data on hormone therapy and suicide attempts among transgender people. To address possible confounding by healthcare utilization, we used prior tetanus-diphtheria-pertussis (TdaP) vaccination as a negative control exposure.ResultsHormone therapy was weakly associated with risk (risk ratio [RR] = 0.9). The negative control exposure was associated with risk (RR = 1.7), suggesting confounding. Based on an assumed prior distribution for the bias parameter, the 95% simulation interval for the distribution of confounding-adjusted RR was (0.17, 1.6), with median 0.5; the 95% credibility interval was similar.ConclusionsWe used dichotomous negative control exposure to identify causal effects when a confounder was unmeasured under strong assumptions. It may be possible to relax assumptions and the negative control exposure could prove helpful for probabilistic bias analyses and Bayesian analyses.
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Project description:The goal of personalized decision making is to map a unit's characteristics to an action tailored to maximize the expected outcome for that unit. Obtaining high-quality mappings of this type is the goal of the dynamic regime literature. In healthcare settings, optimizing policies with respect to a particular causal pathway may be of interest as well. For example, we may wish to maximize the chemical effect of a drug given data from an observational study where the chemical effect of the drug on the outcome is entangled with the indirect effect mediated by differential adherence. In such cases, we may wish to optimize the direct effect of a drug, while keeping the indirect effect to that of some reference treatment. [15] shows how to combine mediation analysis and dynamic treatment regime ideas to defines policies associated with causal pathways and counterfactual responses to these policies. In this paper, we derive a variety of methods for learning high quality policies of this type from data, in a causal model corresponding to a longitudinal setting of practical importance. We illustrate our methods via a dataset of HIV patients undergoing therapy, gathered in the Nigerian PEPFAR program.
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Project description:Dynamic Causal Modeling (DCM) can be used to quantify cognitive function in individuals as effective connectivity. However, ambiguity among subjects in the number and location of discernible active regions prevents all candidate models from being compared in all subjects, precluding the use of DCM as an individual cognitive phenotyping tool. This paper proposes a solution to this problem by treating missing regions in the first-level analysis as missing data, and performing estimation of the time course associated with any missing region using one of four candidate methods: zero-filling, average-filling, noise-filling using a fixed stochastic process, or one estimated using expectation-maximization. The effect of this estimation scheme was analyzed by treating it as a preprocessing step to DCM and observing the resulting effects on model evidence. Simulation studies show that estimation using expectation-maximization yields the highest classification accuracy using a simple loss function and highest model evidence, relative to other methods. This result held for various dataset sizes and varying numbers of model choice. In real data, application to Go/No-Go and Simon tasks allowed computation of signals from the missing nodes and the consequent computation of model evidence in all subjects compared to 62 and 48 percent respectively if no preprocessing was performed. These results demonstrate the face validity of the preprocessing scheme and open the possibility of using single-subject DCM as an individual cognitive phenotyping tool.
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Project description:Causal mediation analysis uses a potential outcomes framework to estimate the direct effect of an exposure on an outcome and its indirect effect through an intermediate variable (or mediator). Causal interpretations of these effects typically rely on sequential ignorability. Because this assumption is not empirically testable, it is important to conduct sensitivity analyses. Sensitivity analyses so far offered for this situation have either focused on the case where the outcome follows a linear model or involve nonparametric or semiparametric models. We propose alternative approaches that are suitable for responses following generalized linear models. The first approach uses a Gaussian copula model involving latent versions of the mediator and the final outcome. The second approach uses a so-called hybrid causal-observational model that extends the association model for the final outcome, providing a novel sensitivity parameter. These models, while still assuming a randomized exposure, allow for unobserved (as well as observed) mediator-outcome confounders that are not affected by exposure. The methods are applied to data from a study of the effect of mother education on dental caries in adolescence.
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Project description:A major concern in any observational study is unmeasured confounding of the relationship between a treatment and outcome of interest. Instrumental variable (IV) analysis methods are able to control for unmeasured confounding. However, IV analysis methods developed for censored time-to-event data tend to rely on assumptions that may not be reasonable in many practical applications, making them unsuitable for use in observational studies. In this report, we develop weighted estimators of the complier average causal effect (CACE) on the restricted mean survival time in the overall population as well as in an evenly matchable population (CACE-m). Our method is able to accommodate instrument-outcome confounding and adjust for covariate-dependent censoring, making it particularly suited for causal inference from observational studies. We establish the asymptotic properties and derive easily implementable asymptotic variance estimators for the proposed estimators. Through simulation studies, we show that the proposed estimators tend to be more efficient than instrument propensity score matching-based estimators or IPIW estimators. We apply our method to compare dialytic modality-specific survival for end stage renal disease patients using data from the U.S. Renal Data System.
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