arXiv subjects

Sean Hennessy

Publications and source records attributed to Sean Hennessy.

6 recordsLinked to original sources

arXiv2026

Optimal Treatment Policy Estimation for Recurrent Events with a Competing Terminal Event: An Instrumented Difference-in-Differences Approach

Learning reproducible and generalizable optimal treatment policies for chronic diseases requires large, representative populations with long-term follow-up. Administrative health data provide a natural starting point, but their use is often limited by unmeasured confounding. We address this by proposing a novel framework based on Instrumented Difference-in-Differences (iDID) to estimate optimal policies for recurrent event outcomes subject to a terminating event. The iDID design is particularly useful in this setting because it leverages policy-induced treatment variation while allowing for persistent unmeasured differences across populations, relying on assumptions that are more plausible for administrative health data than those required by conventional IV or DID approaches. A key feature of our approach is that it explicitly addresses the fundamental challenge of avoiding policies that trivially reduce recurrent adverse events by increasing mortality. We derive two distinct Inverse Probability Weighted identifications and develop a multiply robust estimator that achieves consistency if any one of several subsets of nuisance models is correctly specified. We establish the estimator's consistency and asymptotic normality through large-sample theory and demonstrate its superior finite-sample performance over existing methods via simulation. Finally, we apply this framework to a national Medicare dataset to optimize first-line Type 2 Diabetes strategies, specifically targeting the minimization of disease-related hospitalizations while accounting for survival.

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arXiv2022

Structural mean models for instrumented difference-in-differences

In the standard difference-in-differences research design, the parallel trends assumption may be violated when the relationship between the exposure trend and the outcome trend is confounded by unmeasured confounders. Progress can be made if there is an exogenous variable that (i) does not directly influence the change in outcome means (i.e. the outcome trend) except through influencing the change in exposure means (i.e. the exposure trend), and (ii) is not related to the unmeasured exposure - outcome confounders on the trend scale. Such exogenous variable is called an instrument for difference-in-differences. For continuous outcomes that lend themselves to linear modelling, so-called instrumented difference-in-differences methods have been proposed. In this paper, we will suggest novel multiplicative structural mean models for instrumented difference-in-differences, which allow one to identify and estimate the average treatment effect on count and rare binary outcomes, in the whole population or among the treated, when a valid instrument for difference-in-differences is available. We discuss the identifiability of these models, then develop efficient semi-parametric estimation approaches that allow the use of flexible, data-adaptive or machine learning methods to estimate the nuisance parameters. We apply our proposal on health care data to investigate the risk of moderate to severe weight gain under sulfonylurea treatment compared to metformin treatment, among new users of antihyperglycemic drugs.

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arXiv2022

Robust Causal Inference of Drug-drug Interactions

There is growing interest in developing causal inference methods for multi-valued treatments with a focus on pairwise average treatment effects. Here we focus on a clinically important, yet less-studied estimand: causal drug-drug interactions (DDIs), which quantifies the degree to which the causal effect of drug A is altered by the presence versus the absence of drug B. Confounding adjustment when studying the effects of DDIs can be accomplished via inverse probability of treatment weighting (IPTW), a standard approach originally developed for binary treatments and later generalized to multi-valued treatments. However, this approach generally results in biased results when the propensity score model is misspecified. Motivated by the need for more robust techniques, we propose two empirical likelihood-based weighting approaches that allow for specifying a set of propensity score models, with the second method balancing user-specified covariates directly, by incorporating additional, nonparametric constraints. The resulting estimators from both methods are consistent when the postulated set of propensity score models contains a correct one; this property has been termed multiple robustness. We then evaluate their finite sample performance through simulation. The results demonstrate that the proposed estimators outperform the standard IPTW method in terms of both robustness and efficiency. Finally, we apply the proposed methods to evaluate the impact of renin-angiotensin system inhibitors (RAS-I) on the comparative nephrotoxicity of nonsteroidal anti-inflammatory drugs (NSAID) and opioids, using data derived from electronic medical records from a large multi-hospital health system.

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arXiv2021

Instrumented Difference-in-Differences

Unmeasured confounding is a key threat to reliable causal inference based on observational studies. Motivated from two powerful natural experiment devices, the instrumental variables and difference-in-differences, we propose a new method called instrumented difference-in-differences that explicitly leverages exogenous randomness in an exposure trend to estimate the average and conditional average treatment effect in the presence of unmeasured confounding. We develop the identification assumptions using the potential outcomes framework. We propose a Wald estimator and a class of multiply robust and efficient semiparametric estimators, with provable consistency and asymptotic normality. In addition, we extend the instrumented difference-in-differences to a two-sample design to facilitate investigations of delayed treatment effect and provide a measure of weak identification. We demonstrate our results in simulated and real datasets.

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arXiv2019

Technical Preprint: Rationale and Design of a Planned Observational Study to Evaluate the Impact of Hydrocodone Rescheduling on Opioid Prescribing After Surgery

In October 2014, the US Drug Enforcement Agency (DEA) reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in a prohibition on refills in the initial prescription. While this schedule change was associated with overall decreases in the rate of filled hydrocodone prescriptions and opioid dispensing, available studies conflict regarding its impact on acute opioid prescribing among surgical patients. Here, we present the rationale and design of a planned study to measure the effect of hydrocodone rescheduling using a difference-in-differences design that leverages anticipated variation in the relative impact of this policy on patients treated by surgeons that more or less frequently prescribed hydrocodone products versus other opioids prior to the schedule change. Additionally, we present findings from preliminary study conducted on a subset of our full planned sample to assess for potential differences in outcome trends over the 3 years prior to rescheduling among patients treated by surgeons who commonly prescribed hydrocodone versus those treated by surgeons who rarely prescribed hydrocodone.

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arXiv2015

Selection bias when using instrumental variable methods to compare two treatments but more than two treatments are available

Instrumental variable (IV) methods are widely used to adjust for the bias in estimating treatment effects caused by unmeasured confounders in observational studies. In this manuscript, we provide empirical and theoretical evidence that the IV methods may result in biased treatment effects if applied on a data set in which subjects are preselected based on their received treatments. We frame this as a selection bias problem and propose a procedure that identifies the treatment effect of interest as a function of a vector of sensitivity parameters. We also list assumptions under which analyzing the preselected data does not lead to a biased treatment effect estimate. The performance of the proposed method is examined using simulation studies. We applied our method on The Health Improvement Network (THIN) database to estimate the comparative effect of metformin and sulfonylureas on weight gain among diabetic patients.

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