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The prediction of cancer prognosis and metastatic potential immediately after the initial diagnoses is a major challenge in current clinical research. The relevance of such a signature is clear, as it will free many patients from the agony…

Applications · Statistics 2017-10-17 Royi Jacobovic

The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…

Methodology · Statistics 2025-01-16 Hao Sun , Jerry Li

We develop an empirical Bayes procedure for estimating the cell means in an unbalanced, two-way additive model with fixed effects. We employ a hierarchical model, which reflects exchangeability of the effects within treatment and within…

Methodology · Statistics 2016-05-30 Lawrence D. Brown , Gourab Mukherjee , Asaf Weinstein

An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…

Applications · Statistics 2021-05-03 Helen Barnett , Oliver Boix , Dimintris Kontos , Thomas Jaki

A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential…

Methodology · Statistics 2022-02-04 Emily Roberts , Michael Elliott , Jeremy M. G. Taylor

Approving and assessing new drugs is complex because multiple criteria must be considered simultaneously. A common approach is benefit-risk analysis, often conducted within a Bayesian framework to account for uncertainty and combine data…

Motivated by the increasing use of and rapid changes in array technologies, we consider the prediction problem of fitting a linear regression relating a continuous outcome $Y$ to a large number of covariates $\mathbf {X}$, for example,…

Applications · Statistics 2014-01-13 Philip S. Boonstra , Bhramar Mukherjee , Jeremy M. G. Taylor

The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…

Methodology · Statistics 2024-10-29 Thomas Burnett , Thomas Jaki

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

The use of historical controls offers a valuable alternative when traditional randomized controlled trials are not feasible. However, such approaches may introduce bias due to temporal changes in patient populations, diagnostic criteria,…

Methodology · Statistics 2025-12-24 Marco Ratta , Pavel Mozgunov , Sandrine Boulet , Moreno Ursino

In many clinical trials treatments need to be repeatedly applied as diseases relapse frequently after remission over a long period of time (e.g., 35 weeks). Most research in statistics focuses on the overall trial design, such as sample…

Methodology · Statistics 2014-04-01 Yanxun Xu , Yuan Ji

For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some…

Methodology · Statistics 2023-04-17 Kaspar Rufibach , Lynda Grinsted , Jiang Li , Hans-Jochen Weber , Cheng Zheng , Jiangxiu Zhou

In many clinical trials, outcomes of interest include binary-valued endpoints. It is not uncommon that a binary-valued outcome is dichotomized from a continuous outcome at a threshold of clinical interest. To reach the objective, common…

Applications · Statistics 2021-08-05 Chenchen Ma , Xin Shen , Yongming Qu , Yu Du

With the rapid development of new anti-cancer agents which are cytostatic, new endpoints are needed to better measure treatment efficacy in phase II trials. For this purpose, Von Hoff (1998) proposed the growth modulation index (GMI), i.e.…

Methodology · Statistics 2021-11-01 Li Chen , Mark Burkard , Jianrong Wu , Jill M. Kolesar , Chi Wang

Historical data about disease outcomes can be integrated into the analysis of clinical trials in many ways. We build on existing literature that uses prognostic scores from a predictive model to increase the efficiency of treatment effect…

Methodology · Statistics 2020-12-25 David Walsh , Alejandro Schuler , Diana Hall , Jon Walsh , Charles Fisher

Response-adaptive randomization (RAR) can increase participant benefit in clinical trials, but also complicates statistical analysis. The burn-in period (a non-adaptive initial stage) is commonly used to mitigate this disadvantage, yet…

Methodology · Statistics 2025-10-14 Edwin Y. N. Tang , Stef Baas , Daniel Kaddaj , Lukas Pin , David S. Robertson , Sofía S. Villar

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their…

Longitudinal studies with binary or ordinal responses are widely encountered in various disciplines, where the primary focus is on the temporal evolution of the probability of each response category. Traditional approaches build from the…

Methodology · Statistics 2024-09-04 Jizhou Kang , Athanasios Kottas

We propose a multiple cohort expansion (MUCE) approach as a design or analysis method for phase 1b multiple expansion cohort trials, which are novel first-in-human studies conducted following phase 1a dose escalation. The MUCE design is…

Methodology · Statistics 2025-05-21 Jiaying Lyu , Tianjian Zhou , Shijie Yuan , Wentian Guo , Yuan Ji

Optical phase measurement is a simple example of a quantum--limited measurement problem with important applications in metrology such as gravitational wave detection. The formulation of optimal strategies for such measurements is an…

Quantum Physics · Physics 2012-12-18 K. R. W. Jones