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We conducted a systematic comparison of statistical methods used for the analysis of time-to-event outcomes under various proportional and nonproportional hazard (NPH) scenarios. Our study used data from recently published oncology trials…

Applications · Statistics 2025-02-12 Xinyu Zhang , Erich J. Greene , Ondrej Blaha , Wei Wei

Time-to-event endpoints are central to evaluate treatment efficacy across many disease areas. Many trial protocols include interim analyses within group-sequential designs that control type I error via spending functions or boundary…

Methodology · Statistics 2026-01-19 Edoardo Ratti , Federico L. Perlino , Stefania Galimberti , Maria G. Valsecchi

The first step towards investigating the effectiveness of a treatment via a randomized trial is to split the population into control and treatment groups then compare the average response of the treatment group receiving the treatment to…

Econometrics · Economics 2022-08-30 Hossein Babaei , Sina Alemohammad , Richard Baraniuk

Pragmatic trials increasingly define outcomes using real-world data such as electronic health records, where assessments are collected during routine care rather than at fixed timepoints. Consequently, these uncontrolled assessments may be…

Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment…

Methodology · Statistics 2023-08-11 Marlena S. Bannick , Sonya L. Heltshe , Noah Simon

Both cluster randomized trials and quasi-experimental designs are used to evaluate the impact of health and social policies and interventions. Stepped-wedge cluster randomized trials randomize a staggered adoption approach, while recent…

Methodology · Statistics 2026-04-15 Haidong Lu , Gregg S. Gonsalves , Fan Li , Guanyu Tong , Lee Kennedy-Shaffer

An individualized treatment rule (ITR) tailors treatments to a patient's specific characteristics. However, randomized controlled trials (RCTs) are often underpowered to detect the treatment effect heterogeneity needed for reliable ITR…

Methodology · Statistics 2026-04-14 Yuan Bian , Donglin Zeng , Hyun-Joon Yang , Leanne M. Williams , Yuanjia Wang

Multistate process data are common in studies of chronic diseases such as cancer. These data are ideal for precision medicine purposes as they can be leveraged to improve more refined health outcomes, compared to standard survival outcomes,…

Methodology · Statistics 2022-11-28 Giorgos Bakoyannis

Individualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials…

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In…

Methodology · Statistics 2023-08-28 Thomas Drury , Juan J Abellan , Nicky Best , Ian R. White

Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of, stepped-wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of…

Methodology · Statistics 2018-06-29 Michael Grayling , Adrian Mander , James Wason

A dynamic treatment regimen (DTR) is a pre-specified sequence of decision rules which maps baseline or time-varying measurements on an individual to a recommended intervention or set of interventions. Sequential multiple assignment…

Methodology · Statistics 2019-10-23 Brook Luers , Min Qian , Inbal Nahum-Shani , Connie Kasari , Daniel Almirall

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment…

Methodology · Statistics 2022-10-05 Dasom Lee , Shu Yang , Xiaofei Wang

When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…

Methodology · Statistics 2020-08-03 Johannes Krisam , Dorothea Weber , Richard F. Schlenk , Meinhard Kieser

Clinical trials involving novel immuno-oncology (IO) therapies frequently exhibit survival profiles which violate the proportional hazards assumption due to a delay in treatment effect, and in such settings, the survival curves in the two…

Methodology · Statistics 2021-02-02 Nicholas C. Henderson , Kijoeng Nam , Dai Feng

Sequential multiple assignment randomized trials (SMARTs) have grown in popularity in recent years, and many of their study protocols propose conducting a cost effectiveness analysis of the adaptive strategies embedded within them. The cost…

Clinical trials are complex and usually involve multiple objectives such as controlling type I error rate, increasing power to detect treatment difference, assigning more patients to better treatment, and more. In literature, both…

Statistics Theory · Mathematics 2010-10-20 Hongjian Zhu , Feifang Hu

Many policies involve dynamics in their treatment assignments, where individuals receive sequential interventions over multiple stages. We study estimation of an optimal dynamic treatment regime that guides the optimal treatment assignment…

Econometrics · Economics 2024-09-04 Shosei Sakaguchi

High-dimensional biomarkers such as genomics are increasingly being measured in randomized clinical trials. Consequently, there is a growing interest in developing methods that improve the power to detect biomarker-treatment interactions.…

Methodology · Statistics 2021-04-30 Jixiong Wang , Ashish Patel , James M. S. Wason , Paul J. Newcombe

The analysis of platform trials can be enhanced by utilizing non-concurrent controls. Since including this data might also introduce bias in the treatment effect estimators if time trends are present, methods for incorporating…

Methodology · Statistics 2026-05-21 Pavla Krotka , Martin Posch , Marta Bofill Roig