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The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…

Methodology · Statistics 2025-09-03 Wei Zhang , Zhiwei Zhang , Aiyi Liu

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

Most prostate cancer survivors are confronted with disease-related and treatment-related side effects that impact their quality of life. A tool that combines specific physical activity coaching with the promotion of a healthy lifestyle and…

Surrogate endpoint (SE) for overall survival in cancer patients is essential to improving the efficiency of oncology drug development. In practice, we may discover a new patient level association with survival, based on one or more clinical…

Applications · Statistics 2022-11-08 Wei Zou

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

In oncology clinical trials, characterizing the long-term overall survival (OS) benefit for an experimental drug or treatment regimen (experimental group) is often unobservable if some patients in the control group switch to drugs in the…

Applications · Statistics 2019-08-05 Yuqing Xu , Meijing Wu , Weili He , Qiming Liao , Yabing Mai

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…

Methodology · Statistics 2025-07-17 James M. McGree , Antony M. Overstall , Mark Jones , Robert K. Mahar

An important tool to evaluate the performance of any design is an optimal benchmark proposed by O'Quigley and others (2002, Biostatistics 3(1), 51-56) that provides an upper bound on the performance of a design under a given scenario. The…

Statistics Theory · Mathematics 2018-03-06 Pavel Mozgunov , Thomas Jaki , Xavier Paoletti

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

The FDA's Project Optimus initiative emphasizes patient-centered dose selection in oncology that balances efficacy and safety. We develop a framework for randomized dose optimization studies that uses clinically interpretable utility scores…

Applications · Statistics 2026-03-24 Xuemin Gu , Cong Xu , Lei Xu , Ying Yu

Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…

Applications · Statistics 2016-05-03 Kevin Kunzmann , Meinhard Kieser

Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…

Methodology · Statistics 2024-08-13 Kai Chen , Heng Zhou , J. Jack Lee , Ying Yuan

We propose a frequentist adaptive phase 2 trial design to evaluate the safety and efficacy of three treatment regimens (doses) compared to placebo for four types of helminth (worm) infections. This trial will be carried out in four…

Composite endpoints are widely used in cardiovascular clinical trials to improve statistical efficiency while preserving clinical relevance. The Win Ratio (WR) measure and more general frameworks of Win Statistics have emerged as…

Methodology · Statistics 2025-11-24 Yunhan Mou , Fan Li , Denise Esserman , Yuan Huang

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…

Collecting multiple longitudinal measurements and time-to-event outcomes is a common practice in clinical and epidemiological studies, often focusing on exploring associations between them. Joint modeling is the standard analytical tool for…

Methodology · Statistics 2024-12-10 Taban Baghfalaki , Reza Hashemi , Catherine Helmer , Helene Jacqmin-Gadda

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

Composite endpoints are increasingly used in clinical trials to capture treatment effects across multiple or hierarchically ordered outcomes. Although inference procedures based on win statistics, such as the win ratio, win odds, and net…

Methodology · Statistics 2025-10-28 Xi Fang , Zhiqiang Cao , Fan Li

Effectiveness of immune-oncology chemotherapies has been presented in recent clinical trials. The Kaplan-Meier estimates of the survival functions of the immune therapy and the control often suggested the presence of the lag-time until the…

Applications · Statistics 2024-07-26 Hisato Sunami , Satoshi Hattori