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Practitioners are interested in not only the average causal effect of the treatment on the outcome but also the underlying causal mechanism in the presence of an intermediate variable between the treatment and outcome. However, in many…

Methodology · Statistics 2016-02-04 Peng Ding , Jiannan Lu

Dynamic treatment regimens (DTRs), also known as treatment algorithms or adaptive interventions, play an increasingly important role in many health domains. DTRs are motivated to address the unique and changing needs of individuals by…

Recently a new experimental approach, the hybrid experimental design (HED), was introduced to enable investigators to answer scientific questions about building behavioral interventions in which human-delivered and digital components are…

Methodology · Statistics 2026-02-26 Mengbing Li , Inbal Nahum-Shani , Walter Dempsey

We present a new estimator of the restricted mean survival time in randomized trials where there is right censoring that may depend on treatment and baseline variables. The proposed estimator leverages prognostic baseline variables to…

Statistics Theory · Mathematics 2016-08-22 Iván Díaz , Elizabeth Colantuoni , Daniel F. Hanley , Michael Rosenblum

Group sequential designs enable interim analyses and potential early stopping for efficacy or futility. While these adaptations improve trial efficiency and ethical considerations, they also introduce bias into the adapted analyses. We…

Methodology · Statistics 2025-10-07 G. Caruso , W. F. Rosenberger , P. Mozgunov , N. Flournoy

Randomized controlled trials are considered the gold standard to evaluate the treatment effect (estimand) for efficacy and safety. According to the recent International Council on Harmonisation (ICH)-E9 addendum (R1), intercurrent events…

Methodology · Statistics 2021-11-24 Junxiang Luo , Stephen J. Ruberg , Yongming Qu

Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces…

Methodology · Statistics 2022-02-16 Dasom Lee , Shu Yang , Lin Dong , Xiaofei Wang , Donglin Zeng , Jianwen Cai

We consider a three-level meta-analysis of standardized mean differences. The standard method of estimation uses inverse-variance weights and REML/PL estimation of variance components for the random effects. We introduce new moment-based…

Methodology · Statistics 2024-11-05 Elena Kulinskaya , David C. Hoaglin

While sample sizes in randomized clinical trials are large enough to estimate the average treatment effect well, they are often insufficient for estimation of treatment-covariate interactions critical to studying data-driven precision…

Machine Learning · Statistics 2020-04-22 Steve Yadlowsky , Fabio Pellegrini , Federica Lionetto , Stefan Braune , Lu Tian

In a randomized controlled trial, treatment switching (also called contamination or crossover) occurs when a patient initially assigned to one treatment arm changes to another arm during the course of follow-up. Overlooking treatment…

Methodology · Statistics 2022-09-27 Andrew Ying

Randomized clinical trials are often designed to assess whether a test treatment prolongs survival relative to a control treatment. Increased patient heterogeneity, while desirable for generalizability of results, can weaken the ability of…

Methodology · Statistics 2020-04-30 Devan V. Mehrotra , Rachel Marceau West

As standards of care advance, patients are living longer and once-fatal diseases are becoming manageable. Clinical trials increasingly focus on reducing disease burden, which can be quantified by the timing and occurrence of multiple…

A platform trial is an innovative clinical trial design that uses a master protocol to evaluate multiple treatments, where patients are often assigned to different subsets of treatment arms based on individual characteristics, enrollment…

In clinical trials, a covariate-adjusted response-adaptive (CARA) design allows a subject newly entering a trial a better chance of being allocated to a superior treatment regimen based on cumulative information from previous subjects, and…

Applications · Statistics 2011-06-21 Yuan-chin Ivan Chang , Eunsik Park

When a clinical trial is subject to a series of interim analyses as a result of which the study may be terminated or modified, final frequentist analyses need to take account of the design used. Failure to do so may result in overstated…

Methodology · Statistics 2019-06-28 John Whitehead , Yasin Desai , Thomas Jaki

Parallel processing is a principle which enables simultaneous implementation of anesthesia induction and operating room (OR) turnover with the aim of improving OR utilization. In this article, we study the problem of scheduling surgeries…

Optimization and Control · Mathematics 2022-01-03 Batuhan Celik , Serhat Gul , Melih Celik

Performance monitoring of machine learning (ML)-based risk prediction models in healthcare is complicated by the issue of confounding medical interventions (CMI): when an algorithm predicts a patient to be at high risk for an adverse event,…

Machine Learning · Statistics 2023-04-17 Jean Feng , Alexej Gossmann , Gene Pennello , Nicholas Petrick , Berkman Sahiner , Romain Pirracchio

This research was motivated by studying anti-drug antibody (ADA) formation and its potential impact on long-term benefit of a biologic treatment in a randomized controlled trial, in which ADA status was not only unobserved in the control…

Methodology · Statistics 2021-01-13 Shengchun Kong , Dominik Heinzmann , Sabine Lauer , Tian Lu

In many practical situations, randomly assigning treatments to subjects is uncommon due to feasibility constraints. For example, economic aid programs and merit-based scholarships are often restricted to those meeting specific income or…

We propose a general framework of sequential testing procedures based on $U$-statistics which contains as an example a sequential CUSUM test based on differences in mean but also includes a robust sequential Wilcoxon change point procedure.…

Statistics Theory · Mathematics 2019-12-19 Claudia Kirch , Christina Stoehr
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