arXiv subjects

Issa J. Dahabreh

Publications and source records attributed to Issa J. Dahabreh.

At least 37 records · Page 2Linked to original sources

arXiv2022

Robust Estimation of Loss-Based Measures of Model Performance under Covariate Shift

We present methods for estimating loss-based measures of the performance of a prediction model in a target population that differs from the source population in which the model was developed, in settings where outcome and covariate data are available from the source population but only covariate data are available on a simple random sample from the target population. Prior work adjusting for differences between the two populations has used various weighting estimators with inverse odds or density ratio weights. Here, we develop more robust estimators for the target population risk (expected loss) that can be used with data-adaptive (e.g., machine learning-based) estimation of nuisance parameters. We examine the large-sample properties of the estimators and evaluate finite sample performance in simulations. Last, we apply the methods to data from lung cancer screening using nationally representative data from the National Health and Nutrition Examination Survey (NHANES) and extend our methods to account for the complex survey design of the NHANES.

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arXiv2022

Selection on treatment in the target population of generalizabillity and transportability analyses

Investigators are increasingly using novel methods for extending (generalizing or transporting) causal inferences from a trial to a target population. In many generalizability and transportability analyses, the trial and the observational data from the target population are separately sampled, following a non-nested trial design. In practical implementations of this design, non-randomized individuals from the target population are often identified by conditioning on the use of a particular treatment, while individuals who used other candidate treatments for the same indication or individuals who did not use any treatment are excluded. In this paper, we argue that conditioning on treatment in the target population changes the estimand of generalizability and transportability analyses and potentially introduces serious bias in the estimation of causal estimands in the target population or the subset of the target population using a specific treatment. Furthermore, we argue that the naive application of marginalization-based or weighting-based standardization methods does not produce estimates of any reasonable causal estimand. We use causal graphs and counterfactual arguments to characterize the identification problems induced by conditioning on treatment in the target population and illustrate the problems using simulated data. We conclude by considering the implications of our findings for applied work.

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arXiv2022

Tree-based Subgroup Discovery In Electronic Health Records: Heterogeneity of Treatment Effects for DTG-containing Therapies

The rich longitudinal individual level data available from electronic health records (EHRs) can be used to examine treatment effect heterogeneity. However, estimating treatment effects using EHR data poses several challenges, including time-varying confounding, repeated and temporally non-aligned measurements of covariates, treatment assignments and outcomes, and loss-to-follow-up due to dropout. Here, we develop the Subgroup Discovery for Longitudinal Data (SDLD) algorithm, a tree-based algorithm for discovering subgroups with heterogeneous treatment effects using longitudinal data by combining the generalized interaction tree algorithm, a general data-driven method for subgroup discovery, with longitudinal targeted maximum likelihood estimation. We apply the algorithm to EHR data to discover subgroups of people living with human immunodeficiency virus (HIV) who are at higher risk of weight gain when receiving dolutegravir-containing antiretroviral therapies (ARTs) versus when receiving non dolutegravir-containing ARTs.

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arXiv2022

Global sensitivity analysis for studies extending inferences from a randomized trial to a target population

When individuals participating in a randomized trial differ with respect to the distribution of effect modifiers compared compared with the target population where the trial results will be used, treatment effect estimates from the trial may not directly apply to target population. Methods for extending -- generalizing or transporting -- causal inferences from the trial to the target population rely on conditional exchangeability assumptions between randomized and non-randomized individuals. The validity of these assumptions is often uncertain or controversial and investigators need to examine how violation of the assumptions would impact study conclusions. We describe methods for global sensitivity analysis that directly parameterize violations of the assumptions in terms of potential (counterfactual) outcome distributions. Our approach does not require detailed knowledge about the distribution of specific unmeasured effect modifiers or their relationship with the observed variables. We illustrate the methods using data from a trial nested within a cohort of trial-eligible individuals to compare coronary artery surgery plus medical therapy versus medical therapy alone for stable ischemic heart disease.

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arXiv2022

Systematically Missing Data in Causally Interpretable Meta-Analysis

Causally interpretable meta-analysis combines information from a collection of randomized controlled trials to estimate treatment effects in a target population in which experimentation may not be possible but covariate information can be collected from a simple random sample. In such analyses, a key practical challenge is systematically missing data when some baseline covariates are not collected in all trials. Here, we provide identification results for potential (counterfactual) outcome means and average treatment effects in the target population when covariate data are systematically missing from some of the trials in the meta-analysis. We propose three estimators for the average treatment effect in the target population, examine their asymptotic properties, and show that they have good finite-sample performance in simulation studies. We use the estimators to analyze data from two large lung cancer screening trials and target population data from the National Health and Nutrition Examination Survey (NHANES). To accommodate the complex survey design of the NHANES, we modify the methods to incorporate survey sampling weights and allow for clustering.

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arXiv2022

Extending inferences from a cluster randomized trial to a target population

We describe methods that extend (generalize or transport) causal inferences from cluster randomized trials to a target population of clusters, under a general nonparametric model that allows for arbitrary within-cluster dependence. We propose doubly robust estimators of potential outcome means in the target population that exploit individual-level data on covariates and outcomes to improve efficiency and are appropriate for use with machine learning methods. We illustrate the methods using a cluster randomized trial of influenza vaccination strategies conducted in 818 nursing homes nested in a cohort of 4,475 trial-eligible Medicare-certified nursing homes.

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arXiv2022

Randomized trials and their observational emulations: a framework for benchmarking and joint analysis

A randomized trial and an analysis of observational data designed to emulate the trial sample observations separately, but have the same eligibility criteria, collect information on some shared baseline covariates, and compare the effects of the same treatments on the same outcomes. Treatment effect estimates from the trial and its emulation can be compared to benchmark observational analysis methods. In a simplified setting with complete adherence to the assigned treatment strategy and no loss-to-follow-up, we show that benchmarking relies on an exchangeability condition between the populations underlying the trial and its emulation, to account for differences in the distribution of covariates between them. When this exchangeability condition holds, and the usual conditions needed for the estimates from the trial and its emulation to have a causal interpretation also hold, we derive restrictions on the law of the observed data. When the data are compatible with the restrictions, joint analysis of the trial and its emulation is possible. When the data are incompatible with the restrictions, a discrepancy between (1) estimates based on extending inferences from the trial to the population underlying the emulation and (2) the emulation itself may reflect either inability to benchmark (e.g., due to selective participation into the trial) or a failure of the emulation (e.g., due to unmeasured confounding), but we cannot use the data to determine which is the case. Our analysis reveals how benchmarking attempts combine causal assumptions, data analysis methods, and substantive knowledge to examine the validity of observational analysis methods.

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arXiv2022

Learning about treatment effects in a new target population under transportability assumptions for relative effect measures

Epidemiologists and applied statisticians often believe that relative effect measures conditional on covariates, such as risk ratios and mean ratios, are ``transportable'' across populations. Here, we examine the identification of causal effects in a target population using an assumption that conditional relative effect measures (e.g., conditional risk ratios or mean ratios) are transportable from a trial to the target population. We show that transportability for relative effect measures is largely incompatible with transportability for difference effect measures, unless the treatment has no effect on average or one is willing to make even stronger transportability assumptions, which imply the transportability of both relative and difference effect measures. We then describe how marginal causal estimands in a target population can be identified under the assumption of transportability of relative effect measures, when we are interested in the effectiveness of a new experimental treatment in a target population where the only treatment in use is the control treatment evaluated in the trial. We extend these results to consider cases where the control treatment evaluated in the trial is only one of the treatments in use in the target population, under an additional partial exchangeability assumption in the target population (i.e., a partial assumption of no unmeasured confounding in the target population). We also develop identification results that allow for the covariates needed for transportability of relative effect measures to be only a small subset of the covariates needed to control confounding in the target population. Last, we propose estimators that can be easily implemented in standard statistical software.

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arXiv2022

Efficient and robust methods for causally interpretable meta-analysis: transporting inferences from multiple randomized trials to a target population

We present methods for causally interpretable meta-analyses that combine information from multiple randomized trials to estimate potential (counterfactual) outcome means and average treatment effects in a target population. We consider identifiability conditions, derive implications of the conditions for the law of the observed data, and obtain identification results for transporting causal inferences from a collection of independent randomized trials to a new target population in which experimental data may not be available. We propose an estimator for the potential (counterfactual) outcome mean in the target population under each treatment studied in the trials. The estimator uses covariate, treatment, and outcome data from the collection of trials, but only covariate data from the target population sample. We show that it is doubly robust, in the sense that it is consistent and asymptotically normal when at least one of the models it relies on is correctly specified. We study the finite sample properties of the estimator in simulation studies and demonstrate its implementation using data from a multi-center randomized trial.

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arXiv2021

Estimating subgroup effects in generalizability and transportability analyses

Methods for extending -- generalizing or transporting -- inferences from a randomized trial to a target population involve conditioning on a large set of covariates that is sufficient for rendering the randomized and non-randomized groups exchangeable. Yet, decision-makers are often interested in examining treatment effects in subgroups of the target population defined in terms of only a few discrete covariates. Here, we propose methods for estimating subgroup-specific potential outcome means and average treatment effects in generalizability and transportability analyses, using outcome model-based (g-formula), weighting, and augmented weighting estimators. We consider estimating subgroup-specific average treatment effects in the target population and its non-randomized subset, and provide methods that are appropriate both for nested and non-nested trial designs. As an illustration, we apply the methods to data from the Coronary Artery Surgery Study to compare the effect of surgery plus medical therapy versus medical therapy alone for chronic coronary artery disease in subgroups defined by history of myocardial infarction.

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arXiv2021

Center-specific causal inference with multicenter trials: reinterpreting trial evidence in the context of each participating center

In multicenter randomized trials, when effect modifiers have a different distribution across centers, comparisons between treatment groups that average over centers may not apply to any of the populations underlying the individual centers. Here, we describe methods for reinterpreting the evidence produced by a multicenter trial in the context of the population underlying each center. We describe how to identify center-specific effects under identifiability conditions that are largely supported by the study design and when associations between center membership and the outcome may be present, given baseline covariates and treatment ("center-outcome associations"). We then consider an additional condition of no center-outcome associations given baseline covariates and treatment. We show that this condition can be assessed using the trial data; when it holds, center-specific treatment effects can be estimated using analyses that completely pool information across centers. We propose methods for estimating center-specific average treatment effects, when center-outcome associations may be present and when they are absent, and describe approaches for assessing whether center-specific treatment effects are homogeneous. We evaluate the performance of the methods in a simulation study and illustrate their implementation using data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial.

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arXiv2021

Transporting a prediction model for use in a new target population

We consider methods for transporting a prediction model and assessing its performance for use in a new target population, when outcome and covariate information for model development is available from a simple random sample from the source population, but only covariate information is available on a simple random sample from the target population. We discuss how to tailor the prediction model for use in the target population, how to assess model performance in the target population (e.g., by estimating the target population mean squared error), and how to perform model and tuning parameter selection in the context of the target population. We provide identifiability results for the target population mean squared error of a potentially misspecified prediction model under a sampling design where the source study and the target population samples are obtained separately. We also introduce the concept of prediction error modifiers that can be used to reason about the need for tailoring measures of model performance to the target population and provide an illustration of the methods using simulated data.

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arXiv2020

Causal Interaction Trees: Tree-Based Subgroup Identification for Observational Data

We propose Causal Interaction Trees for identifying subgroups of participants that have enhanced treatment effects using observational data. We extend the Classification and Regression Tree algorithm by using splitting criteria that focus on maximizing between-group treatment effect heterogeneity based on subgroup-specific treatment effect estimators to dictate decision-making in the algorithm. We derive properties of three subgroup-specific treatment effect estimators that account for the observational nature of the data -- inverse probability weighting, g-formula and doubly robust estimators. We study the performance of the proposed algorithms using simulations and implement the algorithms in an observational study that evaluates the effectiveness of right heart catheterization on critically ill patients.

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arXiv2020

Towards causally interpretable meta-analysis: transporting inferences from multiple studies to a target population

We take steps towards causally interpretable meta-analysis by describing methods for transporting causal inferences from a collection of randomized trials to a new target population, one-trial-at-a-time and pooling all trials. We discuss identifiability conditions for average treatment effects in the target population and provide identification results. We show that assuming inferences are transportable from all trials in the collection to the same target population has implications for the law underlying the observed data. We propose average treatment effect estimators that rely on different working models and provide code for their implementation in statistical software. We discuss how to use the data to examine whether transported inferences are homogeneous across the collection of trials, sketch approaches for sensitivity analysis to violations of the identifiability conditions, and describe extensions to address non-adherence in the trials. Last, we illustrate the proposed methods using data from the HALT-C multi-center trial.

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arXiv2019

Extending inferences from a randomized trial to a new target population

When treatment effect modifiers influence the decision to participate in a randomized trial, the average treatment effect in the population represented by the randomized individuals will differ from the effect in other populations. In this tutorial, we consider methods for extending causal inferences about time-fixed treatments from a trial to a new target population of non-participants, using data from a completed randomized trial and baseline covariate data from a sample from the target population. We examine methods based on modeling the expectation of the outcome, the probability of participation, or both (doubly robust). We compare the methods in a simulation study and show how they can be implemented in software. We apply the methods to a randomized trial nested within a cohort of trial-eligible patients to compare coronary artery surgery plus medical therapy versus medical therapy alone for patients with chronic coronary artery disease. We conclude by discussing issues that arise when using the methods in applied analyses.

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arXiv2019

Generalizing causal inferences from randomized trials: counterfactual and graphical identification

When engagement with a randomized trial is driven by factors that affect the outcome or when trial engagement directly affects the outcome independent of treatment, the average treatment effect among trial participants is unlikely to generalize to a target population. In this paper, we use counterfactual and graphical causal models to examine under what conditions we can generalize causal inferences from a randomized trial to the target population of trial-eligible individuals. We offer an interpretation of generalizability analyses using the notion of a hypothetical intervention to "scale-up" trial engagement to the target population. We consider the interpretation of generalizability analyses when trial engagement does or does not directly affect the outcome, highlight connections with censoring in longitudinal studies, and discuss identification of the distribution of counterfactual outcomes via g-formula computation and inverse probability weighting. Last, we show how the methods can be extended to address time-varying treatments, non-adherence, and censoring.

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arXiv2019

Sensitivity analysis using bias functions for studies extending inferences from a randomized trial to a target population

Extending (generalizing or transporting) causal inferences from a randomized trial to a target population requires ``generalizability'' or ``transportability'' assumptions, which state that randomized and non-randomized individuals are exchangeable conditional on baseline covariates. These assumptions are made on the basis of background knowledge, which is often uncertain or controversial, and need to be subjected to sensitivity analysis. We present simple methods for sensitivity analyses that do not require detailed background knowledge about specific unknown or unmeasured determinants of the outcome or modifiers of the treatment effect. Instead, our methods directly parameterize violations of the assumptions using bias functions. We show how the methods can be applied to non-nested trial designs, where the trial data are combined with a separately obtained sample of non-randomized individuals, as well as to nested trial designs, where a clinical trial is embedded within a cohort sampled from the target population. We illustrate the methods using data from a clinical trial comparing treatments for chronic hepatitis C infection.

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arXiv2019

Study designs for extending causal inferences from a randomized trial to a target population

We examine study designs for extending (generalizing or transporting) causal inferences from a randomized trial to a target population. Specifically, we consider nested trial designs, where randomized individuals are nested within a sample from the target population, and non-nested trial designs, including composite dataset designs, where a randomized trial is combined with a separately obtained sample of non-randomized individuals from the target population. We show that the causal quantities that can be identified in each study design depend on what is known about the probability of sampling non-randomized individuals. For each study design, we examine identification of potential outcome means via the g-formula and inverse probability weighting. Last, we explore the implications of the sampling properties underlying the designs for the identification and estimation of the probability of trial participation.

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