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The question of selecting the "best" amongst different choices is a common problem in statistics. In drug development, our motivating setting, the question becomes, for example: what is the dose that gives me a pre-specified risk of…

Statistics Theory · Mathematics 2018-03-15 Pavel Mozgunov , Thomas Jaki

2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…

Methodology · Statistics 2024-04-15 Runjia Li , Liwen Wu , Rachael Liu , Jianchang Lin

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

External information, such as prior information or expert opinions, can play an important role in the design, analysis and interpretation of clinical trials. However, little attention has been devoted thus far to incorporating external…

Applications · Statistics 2013-04-24 Minge Xie , Regina Y. Liu , C. V. Damaraju , William H. Olson

This study examines the application of Bayesian approach in the context of clinical trials, emphasizing their increasing importance in contemporary biomedical research. While conventional frequentist approach provides a foundational basis…

Methodology · Statistics 2026-01-16 Paramahansa Pramanik , Arnab Kumar Maity , Anjan Mandal , Haley Kate Robinson

An important goal of precision medicine is to personalize medical treatment by identifying individuals who are most likely to benefit from a specific treatment. The Likely Responder (LR) framework, which identifies a subpopulation where…

Methodology · Statistics 2026-03-13 Annan Deng , Carole Siegel , Hyung G. Park

The ordinal endpoint is prevalent in clinical studies. For example, for the COVID-19, the most common endpoint used was 7-point ordinal scales. Another example is in phase II cancer studies, efficacy is often assessed as an ordinal variable…

Methodology · Statistics 2022-06-10 Chengxue Zhong , Haitao Pan , Hongyu Miao

Accurate models of clinical actions and their impacts on disease progression are critical for estimating personalized optimal dynamic treatment regimes (DTRs) in medical/health research, especially in managing chronic conditions.…

Methodology · Statistics 2021-02-19 William Hua , Hongyuan Mei , Sarah Zohar , Magali Giral , Yanxun Xu

Due to ethical and economical reasons, sequential single-arm trial designs are used for assessing the therapeutic efficacy of new treatments in phase II trials. Simon's 2-stage design and Lan-DeMets' $\alpha$-spending function method with…

Methodology · Statistics 2023-03-31 Tasuku Inao , Isao Yokota

Given the cost and duration of phase III and phase IV clinical trials, the development of statistical methods for go/no-go decisions is vital. In this paper, we introduce a Bayesian methodology to compute the probability of success based on…

Methodology · Statistics 2020-10-27 Ethan M. Alt , Matthew A. Psioda , Joseph G. Ibrahim

For a trial with primary endpoint overall survival for a molecule with curative potential, statistical methods that rely on the proportional hazards assumption may underestimate the power and the time to final analysis. We show how a cure…

Applications · Statistics 2023-04-17 Kaspar Rufibach , Dominik Heinzmann , Annabelle Monnet

Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…

Methodology · Statistics 2023-05-09 José L. Jiménez , Haiyan Zheng

Therapeutic advancements in oncology have shifted towards targeted therapy based on genomic aberrations. This necessitates innovative statistical approaches in clinical trials, particularly in master protocol studies. Basket trials, a type…

Applications · Statistics 2025-02-12 Antonios Daletzakis , Rutger van den Bor , Vincent van der Noort , Kit CB Roes

Targeted therapies on the basis of genomic aberrations analysis of the tumor have shown promising results in cancer prognosis and treatment. Regardless of tumor type, trials that match patients to targeted therapies for their particular…

Applications · Statistics 2018-04-18 Yanxun Xu , Peter Mueller , Apostolia M Tsimberidou , Donald Berry

In developing products for rare diseases, statistical challenges arise due to the limited number of patients available for participation in drug trials and other clinical research. Bayesian adaptive clinical trial designs offer the…

Applications · Statistics 2019-09-19 Xiao Wu , Yi Xu , Bradley P. Carlin

External pilot trials of complex interventions are used to help determine if and how a confirmatory trial should be undertaken, providing estimates of parameters such as recruitment, retention and adherence rates. The decision to progress…

Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…

Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises…

Applications · Statistics 2022-03-15 Jina Park , Wenjing Hu , Ick Hoon Jin , Hao Liu , Yong Zang

One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more…

Applications · Statistics 2020-09-15 Anh Nguyen Duc , Dominik Heinzmann , Claude Berge , Marcel Wolbers

Practical employment of Bayesian trial designs is still rare. Even if accepted in principle, the regulators have commonly required that such designs be calibrated according to an upper bound for the frequentist type I error rate. This…

Methodology · Statistics 2026-03-25 Elja Arjas , Dario Gasbarra