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Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence…

Statistics Theory · Mathematics 2020-05-28 Andrea Arfé , Brian Alexander , Lorenzo Trippa

Clinical trials usually involve sequential patient entry. When designing a clinical trial, it is often desirable to include a provision for interim analyses of accumulating data with the potential for stopping the trial early. We review…

Methodology · Statistics 2023-03-13 Tianjian Zhou , Yuan Ji

We propose a restricted win probability estimand for comparing treatments in a randomized trial with a time-to-event outcome. We also propose Bayesian estimators for this summary measure as well as the unrestricted win probability. Bayesian…

Methodology · Statistics 2024-11-06 Michelle Leeberg , Xianghua Luo , Thomas A. Murray

Bayesian adaptive designs enable flexible clinical trials by adapting features based on accumulating data. Among these, Bayesian Response-Adaptive Randomization (BRAR) skews patient allocation towards more promising treatments based on…

Methodology · Statistics 2025-12-05 Daniel Kaddaj , Stef Baas , Edwin Y. N. Tang , David S. Robertson , Lukas Pin , Sofía S. Villar

We propose a Bayesian Sequential procedure to test hypotheses concerning the Relative Risk between two specific treatments based on the binary data obtained from the two-arm clinical trial. Our development is based on the optimal sequential…

Methodology · Statistics 2025-04-07 Jiayue Wang , Ben Boukai

A constrained Markov decision process (CMDP) approach is developed for response-adaptive procedures in clinical trials with binary outcomes. The resulting CMDP class of Bayesian response -- adaptive procedures can be used to target a…

Methodology · Statistics 2024-01-31 Stef Baas , Aleida Braaksma , Richard J. Boucherie

Randomized clinical trials are considered the gold standard for estimating causal effects. Nevertheless, in studies that are aimed at examining adverse effects of interventions, such trials are often impractical because of ethical and…

Methodology · Statistics 2020-01-20 Anthony D. Scotina , Andrew R. Zullo , Robert J. Smith , Roee Gutman

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…

Methodology · Statistics 2017-11-16 Kirsten Schorning , Maria Konstantinou

For many rare diseases with no approved preventive interventions, promising interventions exist, yet it has been difficult to conduct a pivotal phase 3 trial that could provide direct evidence demonstrating a beneficial effect on the target…

Given the prominence of targeted therapy and immunotherapy in cancer treatment, it becomes imperative to consider heterogeneity in patients' responses to treatments, which contributes greatly to the widely used proportional hazard…

Methodology · Statistics 2024-09-01 Powei Chen , Siying Hu , Haojin Zhou

The widespread adoption of online randomized controlled experiments (A/B Tests) for decision-making has created ongoing capacity constraints which necessitate interim analyses. As a consequence, platform users are increasingly motivated to…

Applications · Statistics 2025-11-11 Abbas Zaidi , Rina Friedberg , Samir Khan , Yao-Yang Leow , Maulik Soneji , Houssam Nassif , Richard Mudd

Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…

Methodology · Statistics 2022-10-21 Liwen Wu , Qing Li , Mengya Liu , Jianchang Lin

In response to the U.S.\ Food and Drug Administration's (FDA) Project Optimus, a paradigm shift is underway in the design of early-phase oncology trials. To accelerate drug development, seamless Phase I/II designs have gained increasing…

Methodology · Statistics 2025-11-04 Kana Makino , Natsumi Makigusa , Masahiro Kojima

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

Phase III randomized clinical trials play a monumentally critical role in the evaluation of new medical products. Because of the intrinsic nature of uncertainty embedded in our capability in assessing the efficacy of a medical product,…

Methodology · Statistics 2019-02-25 Changyu Shen , Xiaochun Li

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development…

Methodology · Statistics 2019-01-25 Tim Friede , Nigel Stallard , Nicholas Parsons

Precision medicine promises to transform health care by offering individualised treatments that dramatically improve clinical outcomes. A necessary prerequisite is to identify subgroups of patients who respond differently to different…

Machine Learning · Computer Science 2026-03-03 Adam Marcus , Paul Agapow

Adaptive designs for multi-armed clinical trials have become increasingly popular recently in many areas of medical research because of their potential to shorten development times and to increase patient response. However, developing…

Applications · Statistics 2017-03-16 Adam Smith , Sofia S. Villar

Recently, a new testing approach for response-adaptive clinical trials was proposed based on the allocation probabilities (AP) rather than the outcome data. While original work on the AP test focused on binary and normal endpoints and…

Methodology · Statistics 2026-05-11 Stina Zetterstrom , David S. Robertson , Thomas Jaki , Sofía S. Villar
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