arXiv subjects

Nicholas T. Williams

Publications and source records attributed to Nicholas T. Williams.

10 recordsLinked to original sources

arXiv2026

Modified treatment policies that depend on the natural history of treatment

Longitudinal modified treatment policies (LMTP) are a class of interventions that allow the definition, identification, and estimation of causal effects in general settings, such as with continuous or multivariate exposures, treatment regimens that require grace periods. Targeted machine learning estimators (i.e., double/debiased) have been formulated for LMTPs that assign the exposure at time $t$ as a function of the natural value of treatment at time $t$. However, important applications such as estimating the effect of a delay in the start of a treatment require formulating LMTPs that depend not only on the natural value of treatment at time $t$ but also on the \textit{history} of the natural value of treatment prior to time $t$. This paper develops targeted learning estimators for this general case. We discuss the definition of the effects, and propose estimators that use an augmented-data version of the sequential regression form of the longitudinal g-computation formula. Our estimators are based on the efficient influence function and provide $\sqrt{n}$ inference under standard doubly robust rate assumptions on the convergence of the outcome and treatment regressions. We apply the new estimators to assess the effect of delaying a risky pain treatment by one month on 12-month incidence of opioid use disorder.

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arXiv2026

crumble: A comprehensive framework for modern causal mediation analysis with intermediate confounding

Causal mediation analysis is widely used to investigate how causal effects operate through specific pathways linking treatments or exposures to outcomes. Recently, \texttt{crumble} was developed to enable nonparametric estimation of several mediation parameters, even when mediators are continuous and/or multi-dimensional or when treatments are non-binary. But a practical and accessible guide to using \texttt{crumble} -- one that does not require deep familiarity with mediation analysis or semiparametric theory -- is currently lacking. This tutorial aims to an accessible introduction to \texttt{crumble} while minimizing technical complexity. We first review the mediation parameters implemented in \texttt{crumble} -- natural direct and indirect effects, randomized interventional effects, and recanting-twin effects. For each, we give the definition, interpretation, identification assumptions, and suitability in the presence or absence of intermediate confounding. Then, we demonstrate the usage of \texttt{crumble} by examining an example configuration. Next, we describe how \texttt{crumble} accommodates non-binary treatments through modified treatment policies. Finally, we illustrate the practical use of \texttt{crumble} through two case studies -- one with a binary treatment and one with a non-binary treatment -- based on the Job Search Intervention Study data.

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arXiv2025

Computationally and statistically efficient estimation of time-smoothed counterfactual curves

Longitudinal causal inference is concerned with defining, identifying, and estimating the effect of a time-varying intervention on a time-varying outcome that is indexed by a follow-up time. In an observational study, Robins's generalized g-formula can identify causal effects induced by a broad class of time-varying interventions. Various methods for estimating the generalized g-formula have been posed for different outcome types, such as a failure event indicator by a specified time (e.g. mortality by 5 year follow-up), as well as continuous or dichotomous/multi-valued outcomes measures at a specified time (e.g. blood pressure in mm/hg or an indicator of high blood pressure at 5-year follow-up). Multiply-robust, data-adaptive estimators leverage flexible nonparametric estimation algorithms while allowing for statistical inference. However, extant methods do not accommodate time-smoothing when multiple outcomes are measured over time, which can lead to substantial loss of precision. We propose a novel multiply-robust estimator of the generalized g-formula that accommodates time-smoothing over numerous available outcome measures. Our approach accommodates any intervention that can be described as a Longitudinal Modified Treatment Policy, a flexible class suitable for binary, multi-valued, and continuous longitudinal treatments. Our method produces an estimate of the effect curve: the causal effect of the intervention on the outcome at each measurement time, taking into account censoring and non-monotonic outcome missingness patterns. In simulations we find that the proposed algorithm outperforms extant multiply-robust approaches for effect curve estimation in scenarios with high degrees of outcome missingness and when there is strong confounding. We apply the method to study longitudinal effects of union membership on wages.

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arXiv2025

Riesz representers for the rest of us

The application of semiparametric efficient estimators, particularly those that leverage machine learning, is rapidly expanding within epidemiology and causal inference. This literature is increasingly invoking the Riesz representation theorem and Riesz regression. This paper aims to introduce the Riesz representation theorem to an epidemiologic audience, explaining what it is and why it's useful, using step-by-step worked examples.

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arXiv2025

General targeted machine learning for modern causal mediation analysis

Causal mediation analyses investigate the mechanisms through which causes exert their effects, and are therefore central to scientific progress. The literature on the non-parametric definition and identification of mediational effects in rigourous causal models has grown significantly in recent years, and there has been important progress to address challenges in the interpretation and identification of such effects. Despite great progress in the causal inference front, statistical methodology for non-parametric estimation has lagged behind, with few or no methods available for tackling non-parametric estimation in the presence of multiple, continuous, or high-dimensional mediators. In this paper we show that the identification formulas for six popular non-parametric approaches to mediation analysis proposed in recent years can be recovered from just two statistical estimands. We leverage this finding to propose an all-purpose one-step estimation algorithm that can be coupled with machine learning in any mediation study that uses any of these six definitions of mediation. The estimators have desirable properties, such as $\sqrt{n}$-convergence and asymptotic normality. Estimating the first-order correction for the one-step estimator requires estimation of complex density ratios on the potentially high-dimensional mediators, a challenge that is solved using recent advancements in so-called Riesz learning. We illustrate the properties of our methods in a simulation study and illustrate its use on real data to estimate the extent to which pain management practices mediate the total effect of having a chronic pain disorder on opioid use disorder.

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arXiv2024

Longitudinal Generalizations of the Average Treatment Effect on the Treated for Multi-valued and Continuous Treatments

The Average Treatment Effect on the Treated (ATT) is a common causal parameter defined as the average effect of a binary treatment among the subset of the population receiving treatment. We propose a novel family of parameters, Generalized ATTs (GATTs), that generalize the concept of the ATT to longitudinal data structures, multi-valued or continuous treatments, and conditioning on arbitrary treatment subsets. We provide a formal causal identification result that expresses the GATT in terms of sequential regressions, and derive the efficient influence function of the parameter, which defines its semi-parametric efficiency bound. Efficient semi-parametric inference of the GATT requires estimating the ratios of functions of conditional probabilities (or densities); we propose directly estimating these ratios via empirical loss minimization, drawing on the theory of Riesz representers. Simulations suggest that estimation of the density ratios using Riesz representation have better stability in finite samples. Lastly, we illustrate the use of our methods to evaluate the effect of chronic pain management strategies on the development of opioid use disorder among Medicare patients with chronic pain.

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arXiv2024

Improving efficiency in transporting average treatment effects

We develop flexible, semiparametric estimators of the average treatment effect (ATE) transported to a new population ("target population") that offer potential efficiency gains. Transport may be of value when the ATE may differ across populations. We consider the setting where differences in the ATE are due to differences in the distribution of baseline covariates that modify the treatment effect ("effect modifiers"). First, we propose a collaborative one-step semiparametric estimator that can improve efficiency. This approach does not require researchers to have knowledge about which covariates are effect modifiers and which differ in distribution between the populations, but does require all covariates to be measured in the target population. Second, we propose two one-step semiparametric estimators that assume knowledge of which covariates are effect modifiers and which are both effect modifiers and differentially distributed between the populations. These estimators can be used even when not all covariates are observed in the target population; one requires that only effect modifiers are observed, and the other requires that only those modifiers that are also differentially distributed are observed. We use simulation to compare finite sample performance across our proposed estimators and an existing semiparametric estimator of the transported ATE, including in the presence of practical violations of the positivity assumption. Lastly, we apply our proposed estimators to a large-scale housing trial.

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arXiv2024

Two-Step Targeted Minimum-Loss Based Estimation for Non-Negative Two-Part Outcomes

Non-negative two-part outcomes are defined as outcomes with a density function that have a zero point mass but are otherwise positive. Examples, such as healthcare expenditure and hospital length of stay, are common in healthcare utilization research. Despite the practical relevance of non-negative two-part outcomes, very few methods exist to leverage knowledge of their semicontinuity to achieve improved performance in estimating causal effects. In this paper, we develop a nonparametric two-step targeted minimum-loss based estimator (denoted as hTMLE) for non-negative two-part outcomes. We present methods for a general class of interventions referred to as modified treatment policies, which can accommodate continuous, categorical, and binary exposures. The two-step TMLE uses a targeted estimate of the intensity component of the outcome to produce a targeted estimate of the binary component of the outcome that may improve finite sample efficiency. We demonstrate the efficiency gains achieved by the two-step TMLE with simulated examples and then apply it to a cohort of Medicaid beneficiaries to estimate the effect of chronic pain and physical disability on days' supply of opioids.

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arXiv2024

Associations between pain-management treatments and opioid use disorder risk among Medicaid patients

Introduction: Chronic pain patients are at increased risk of opioid-misuse. Less is known about the unique risk conferred by each pain-management treatment, as treatments are typically implemented together, confounding their independent effects. We estimated the extent to which pain-management strategies were associated with risk of incident opioid use disorder (OUD) for those with chronic pain, controlling for baseline demographic and clinical confounding variables and holding other pain-management treatments at their observed levels. Methods: We used data from two chronic pain subgroups within a cohort of non-pregnant Medicaid patients aged 35-64 years, 2016-2019, from 25 states: 1) those with a chronic pain condition co-morbid with physical disability (N=6,133) or 2) those with chronic pain without disability (N=67,438). We considered 9 pain-management treatments: prescription opioid i) dose and ii) duration; iii) number of opioid prescribers; opioid co-prescription with iv) benzodiazepines, v) muscle relaxants, and vi) gabapentinoids; vii) non-opioid pain prescription, viii) physical therapy, and ix) other pain treatment modality. Our outcome was incident OUD. Results: Having an opioid and gabapentin co-prescription or an opioid and benzodiazepine co-prescription was statistically significantly associated with a 16-46% increased risk of OUD. Opioid dose and duration also were significantly associated with increased risk of OUD. Physical therapy was significantly associated with an 11% decreased risk of OUD in the subgroup with chronic pain but no disability. Conclusions: Co-prescription of opioids with either gabapentin or benzodiazepines may substantially increase risk of OUD. More positively, physical therapy may be a relatively accessible and safe pain-management strategy.

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arXiv2024

Learning Optimal Dynamic Treatment Regimes from Longitudinal Data

Studies often report estimates of the average treatment effect. While the ATE summarizes the effect of a treatment on average, it does not provide any information about the effect of treatment within any individual. A treatment strategy that uses an individual's information to tailor treatment to maximize benefit is known as an optimal dynamic treatment rule. Treatment, however, is typically not limited to a single point in time; consequently, learning an optimal rule for a time-varying treatment may involve not just learning the extent to which the comparative treatments' benefits vary across the characteristics of individuals, but also learning the extent to which the comparative treatments' benefits vary as relevant circumstances evolve within an individual. The goal of this paper is to provide a tutorial for estimating ODTR from longitudinal observational and clinical trial data for applied researchers. We describe an approach that uses a doubly-robust unbiased transformation of the conditional average treatment effect. We then learn a time-varying ODTR for when to increase buprenorphine-naloxone dose to minimize return-to-regular-opioid-use among patients with opioid use disorder. Our analysis highlights the utility of ODTRs in the context of sequential decision making: the learned ODTR outperforms a clinically defined strategy.

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