arXiv subjects

Daniel Scharfstein

Publications and source records attributed to Daniel Scharfstein.

5 recordsLinked to original sources

arXiv2026

Inferring Comprehensive Cohort Causal Effects in the Presence of Unmeasured Confounding and Missing Outcomes

This paper presents a methodological framework for estimating the comprehensive cohort causal effect (CCCE) in mixed-design clinical studies that combine randomized controlled trials (RCTs) and parallel observational study (OBS). Our approach is designed to evaluate robustness against unmeasured confounding in the OBS arm and to handle outcomes that are missing at random in either the RCT or OBS arm. By employing a semiparametric theory-based sensitivity analysis framework, we derive the efficient influence function for the CCCE, parameterized by sensitivity parameters. We propose a one-step bias-corrected estimator that allows for flexible modeling and establish conditions under which our CCCE estimator is $\sqrt{n}$-consistent. To illustrate our methods, we apply them to the TOIB study, which evaluates the efficacy and safety of oral versus topical ibuprofen in managing chronic knee pain among older adults. We also evaluate the performance of the proposed methodology in a realistic simulation study.

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arXiv2024

Addressing the Influence of Unmeasured Confounding in Observational Studies with Time-to-Event Outcomes: A Semiparametric Sensitivity Analysis Approach

In this paper, we develop a semiparametric sensitivity analysis approach designed to address unmeasured confounding in observational studies with time-to-event outcomes. We target estimation of the marginal distributions of potential outcomes under competing exposures using influence function-based techniques. We derive the non-parametric influence function for uncensored data and map the uncensored data influence function to the observed data influence function. Our methodology is motivated by and applied to an observational study evaluating the effectiveness of radical prostatectomy (RP) versus external beam radiotherapy with androgen deprivation (EBRT+AD) for the treatment of prostate cancer. We also present a realistic simulation study demonstrating the finite-sample properties of our estimation procedure.

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arXiv2023

Estimands in Real-World Evidence Studies

A Real-World Evidence (RWE) Scientific Working Group (SWG) of the American Statistical Association Biopharmaceutical Section (ASA BIOP) has been reviewing statistical considerations for the generation of RWE to support regulatory decision-making. As part of the effort, the working group is addressing estimands in RWE studies. Constructing the right estimand -- the target of estimation -- which reflects the research question and the study objective, is one of the key components in formulating a clinical study. ICH E9(R1) describes statistical principles for constructing estimands in clinical trials with a focus on five attributes -- population, treatment, endpoints, intercurrent events, and population-level summary. However, defining estimands for clinical studies using real-world data (RWD), i.e., RWE studies, requires additional considerations due to, for example, heterogeneity of study population, complexity of treatment regimes, different types and patterns of intercurrent events, and complexities in choosing study endpoints. This paper reviews the essential components of estimands and causal inference framework, discusses considerations in constructing estimands for RWE studies, highlights similarities and differences in traditional clinical trial and RWE study estimands, and provides a roadmap for choosing appropriate estimands for RWE studies.

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arXiv2019

A Bayesian Nonparametric Approach for Evaluating the Causal Effect of Treatment in Randomized Trials with Semi-Competing Risks

We develop a Bayesian nonparametric (BNP) approach to evaluate the causal effect of treatment in a randomized trial where a nonterminal event may be censored by a terminal event, but not vice versa (i.e., semi-competing risks). Based on the idea of principal stratification, we define a novel estimand for the causal effect of treatment on the nonterminal event. We introduce identification assumptions, indexed by a sensitivity parameter, and show how to draw inference using our BNP approach. We conduct simulation studies and illustrate our methodology using data from a brain cancer trial.

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arXiv2016

On the analysis of tuberculosis studies with intermittent missing sputum data

In randomized studies evaluating treatments for tuberculosis (TB), individuals are scheduled to be routinely evaluated for the presence of TB using sputum cultures. One important endpoint in such studies is the time of culture conversion, the first visit at which a patient's sputum culture is negative and remains negative. This article addresses how to draw inference about treatment effects when sputum cultures are intermittently missing on some patients. We discuss inference under a novel benchmark assumption and under a class of assumptions indexed by a treatment-specific sensitivity parameter that quantify departures from the benchmark assumption. We motivate and illustrate our approach using data from a randomized trial comparing the effectiveness of two treatments for adult TB patients in Brazil.

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