arXiv subjects

Mats Stensrud

Publications and source records attributed to Mats Stensrud.

6 recordsLinked to original sources

arXiv2026

Trust Me, I'm a Doctor?

Clinical trials usually target average treatment effects, but treatment decisions are made for individuals. This tension motivates a common criticism of evidence-based medicine: a treatment that is beneficial on average may be inappropriate for a particular patient, and skilled physicians may outperform rigid adherence to the strategy that performed best in a randomized trial. We consider how randomized and observational data from the same target population can be used to assess that possibility. Specifically, we study settings in which trial and/or observational data yield estimates of average outcomes under `treat all', `treat none', and usual care strategies in the population of interest. We derive sharp bounds on the proportion of encounters with physicians whose personal strategies outperform the better of `treat all' or `treat none' under the assumption that no physician's strategy is worse than always choosing the worse performing of `treat all' and `treat none'. These results clarify when clinical data support relying on physician discretion over the trial-average recommendation and when stronger justification is required.

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arXiv2026

Causal Inference for All: Marginal Estimands for Outcomes Truncated by Death

In longitudinal studies, outcomes of interest are often truncated by death, meaning that they are only observed or well-defined conditional on intercurrent events such as survival. Existing strategies face a trade-off: causally interpretable estimands, such as survivor average causal effects, target a latent subgroup, whereas while-alive and composite summaries apply to the full population but are difficult to interpret as causal effects on the non-mortality outcome. We address these challenges by introducing methodology for a new set of estimands that (i) concern the entire population, (ii) remain causally interpretable, and (iii) leverage the longitudinal data commonly available in studies with outcomes truncated by death. The set of estimands includes single-world marginal separable effects that generalize conditional separable effects to full-population summaries. We develop identification and estimation results for these estimands and apply the methodology in a reanalysis of a prostate cancer trial, highlighting how different estimands can yield different treatment conclusions.

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arXiv2026

Causal Vaccine Effects on Post-infection Outcomes in the Naturally Infected

Understanding vaccine effects on post-infection outcomes is critical for evaluating the full value proposition of a vaccine. However, defining appropriate causal effects on such outcomes is challenging because infection is affected by vaccination. Existing principal stratification approaches focus on the \emph{Doomed} stratum, individuals who would be infected regardless of vaccine receipt. For many relevant outcomes, however, this estimand will understate vaccine benefit by excluding individuals whose adverse post-infection outcomes are improved because vaccination prevented infection. We therefore propose causal estimands for post-infection outcomes in the \emph{Naturally Infected}, individuals who would be infected in absence of vaccine. We derive bounds under minimal assumptions and give point identification results under an exclusion restriction and/or a partial principal ignorability assumption. For point-identified settings, we develop efficient one-step estimators with robustness properties under inconsistent nuisance parameter estimation. We further show under what conditions the same identification functional can be interpreted as targeting an effect among individuals exposed to a sufficiently infectious dose of the pathogen, thereby avoiding direct reliance on cross-world parameters and fundamentally untestable causal assumptions. Simulations show that the bounds are valid but often wide, and that the point estimators perform well when their identifying assumptions hold. In a reanalysis of a rotavirus vaccine trial, marginal and Doomed-stratum analyses showed little evidence of an effect on antibiotic use, whereas analyses targeting the Naturally Infected suggested a protective effect under principal ignorability-based assumptions.

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arXiv2026

Proximal Causal Inference for Conditional Separable Effects

Scientists regularly pose questions about treatment effects on outcomes conditional on a post-treatment event. However, causal inference in such settings requires care, even in perfectly executed randomized experiments. Recently, the conditional separable effect (CSE) was proposed as an interventionist estimand that corresponds to scientifically meaningful questions in these settings. However, existing results for the CSE require no unmeasured confounding between the outcome and post-treatment event, an assumption frequently violated in practice. In this work, we address this concern by developing new identification and estimation results for the CSE that allow for unmeasured confounding. We establish nonparametric identification of the CSE in observational and experimental settings with time-varying confounders, provided that certain proxy variables for hidden common causes of the post-treatment event and outcome are available. For inference, we characterize an influence function for the CSE under a semiparametric model where nuisance functions are a priori unrestricted. Using modern machine learning methods, we construct nonparametric nuisance function estimators and establish convergence rates that improve upon existing results. Moreover, we develop a consistent, asymptotically linear, and locally semiparametric efficient estimator of the CSE. We illustrate our framework with simulation studies and a real-world cancer therapy trial.

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arXiv2025

Target trial emulation without matching: a more efficient approach for evaluating vaccine effectiveness using observational data

Real-world vaccine effectiveness has increasingly been studied using matching-based approaches, particularly in observational cohort studies following the target trial emulation framework. Although matching is appealing in its simplicity, it suffers important limitations in terms of clarity of the target estimand and the efficiency or precision with which is it estimated. Scientifically justified causal estimands of vaccine effectiveness may be difficult to define owing to the fact that vaccine uptake varies over calendar time when infection dynamics may also be rapidly changing. We propose a causal estimand of vaccine effectiveness that summarizes vaccine effectiveness over calendar time, similar to how vaccine efficacy is summarized in a randomized controlled trial. We describe the identification of our estimand, including its underlying assumptions, and propose simple-to-implement estimators based on two hazard regression models. We apply our proposed estimator in simulations and in a study to assess the effectiveness of the Pfizer-BioNTech COVID-19 vaccine to prevent infections with SARS-CoV2 in children 5-11 years old. In both settings, we find that our proposed estimator yields similar scientific inferences while providing significant efficiency gains over commonly used matching-based estimators.

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arXiv2023

Distinguishing immunological and behavioral effects of vaccination

The interpretation of vaccine efficacy estimands is subtle, even in randomized trials designed to quantify immunological effects of vaccination. In this article, we introduce terminology to distinguish between different vaccine efficacy estimands and clarify their interpretations. This allows us to explicitly consider immunological and behavioural effects of vaccination, and establish that policy-relevant estimands can differ substantially from those commonly reported in vaccine trials. We further show that a conventional vaccine trial allows identification and estimation of different vaccine estimands under plausible conditions, if one additional post-treatment variable is measured. Specifically, we utilize a ``belief variable'' that indicates the treatment an individual believed they had received. The belief variable is similar to ``blinding assessment'' variables that are occasionally collected in placebo-controlled trials in other fields. We illustrate the relations between the different estimands, and their practical relevance, in numerical examples based on an influenza vaccine trial.

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