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Uri Obolski

Publications and source records attributed to Uri Obolski.

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Nonparametric bounds for vaccine effects in randomized trials

Vaccine randomized trials are typically designed to be blinded, ensuring that the estimated vaccine efficacy (VE) reflects the immunological effect of the vaccine. When blinding is broken, however, the estimated VE reflects not only the immunological effect but also behavioral effects stemming from participants' awareness of their treatment status. Recent work has proposed alternative causal estimands to the standard VE to address this issue, but their point identification results require a strong assumption: the absence of unmeasured common causes of infection risk and participants' belief about whether they received the vaccine. Personality traits, for example, may plausibly violate this assumption. We relax this assumption and derive nonparametric causal bounds for different types of VE. We construct these bounds using two approaches: linear programming-based and monotonicity-based methods. We further consider several possible causal structures for vaccine trials and show how the nonparametric bounds differ across these scenarios. Finally, we illustrate the performance of the proposed bounds using fully synthetic data and a semi-synthetic data example based on a COVID-19 vaccine trial.

stat.ME

Causal effects on non-terminal event time with application to antibiotic usage and future resistance

Comparing future antibiotic resistance levels resulting from different antibiotic treatments is challenging because some patients may survive only under one of the antibiotic treatments. We embed this problem within a semi-competing risks approach to study the causal effect on resistant infection, treated as a non-terminal event time. We argue that existing principal stratification estimands for such problems exclude patients for whom a causal effect is well-defined and is of clinical interest. Therefore, we present a new principal stratum, the infected-or-survivors (ios). The ios is the subpopulation of patients who would have survived or been infected under both antibiotic treatments. This subpopulation is more inclusive than previously defined subpopulations. We target the causal effect among these patients, which we term the feasible-infection causal effect (FICE). We develop large-sample bounds under novel assumptions, and discuss the plausibility of these assumptions in our application. As an alternative, we derive FICE identification using two illness-death models with a bivariate frailty random variable. These two models are connected by a cross-world correlation parameter. Estimation is performed by an expectation-maximization algorithm followed by a Monte Carlo procedure. We apply our methods to detailed clinical data obtained from a hospital setting.

stat.ME

Inherent Inconsistencies of Feature Importance

The rapid advancement and widespread adoption of machine learning-driven technologies have underscored the practical and ethical need for creating interpretable artificial intelligence systems. Feature importance, a method that assigns scores to the contribution of individual features on prediction outcomes, seeks to bridge this gap as a tool for enhancing human comprehension of these systems. Feature importance serves as an explanation of predictions in diverse contexts, whether by providing a global interpretation of a phenomenon across the entire dataset or by offering a localized explanation for the outcome of a specific data point. Furthermore, feature importance is being used both for explaining models and for identifying plausible causal relations in the data, independently from the model. However, it is worth noting that these various contexts have traditionally been explored in isolation, with limited theoretical foundations. This paper presents an axiomatic framework designed to establish coherent relationships among the different contexts of feature importance scores. Notably, our work unveils a surprising conclusion: when we combine the proposed properties with those previously outlined in the literature, we demonstrate the existence of an inconsistency. This inconsistency highlights that certain essential properties of feature importance scores cannot coexist harmoniously within a single framework.

cs.LG

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.

stat.AP

DOPE: D-Optimal Pooling Experimental design with application for SARS-CoV-2 screening

Testing individuals for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen causing the coronavirus disease 2019 (COVID-19), is crucial for curtailing transmission chains. Moreover, rapidly testing many potentially infected individuals is often a limiting factor in controlling COVID-19 outbreaks. Hence, pooling strategies, wherein individuals are grouped and tested simultaneously, are employed. We present a novel pooling strategy that implements D-Optimal Pooling Experimental design (DOPE). DOPE defines optimal pooled tests as those maximizing the mutual information between data and infection states. We estimate said mutual information via Monte-Carlo sampling and employ a discrete optimization heuristic for maximizing it. DOPE outperforms common pooling strategies both in terms of lower error rates and fewer tests utilized. DOPE holds several additional advantages: it provides posterior distributions of the probability of infection, rather than only binary classification outcomes; it naturally incorporates prior information of infection probabilities and test error rates; and finally, it can be easily extended to include other, newly discovered information regarding COVID-19. Hence, we believe that implementation of Bayesian D-optimal experimental design holds a great promise for the efforts of combating COVID-19 and other future pandemics.

stat.AP