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The effects of treatments may differ between persons with different characteristics. Addressing such treatment heterogeneity is crucial to investigate whether patients with specific characteristics are likely to benefit from a new…

Methodology · Statistics 2024-03-29 Xynthia Kavelaars , Joris Mulder , Maurits Kaptein

Unblinded sample size re-estimation (SSR) is often planned in a clinical trial when there is large uncertainty about the true treatment effect. For Proof-of Concept (PoC) in a Phase II dose finding study, contrast test can be adopted to…

Methodology · Statistics 2022-11-11 Qingyang Liu , Guanyu Hu , Binqi Ye , Susan Wang , Yaoshi Wu

Estimating the causal effect of time-varying treatments on survival outcomes is a challenging task in many domains, particularly in medicine where treatment protocols adapt over time. While recent advances in representation learning have…

Machine Learning · Statistics 2025-05-06 Ayoub Abraich

FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…

Applications · Statistics 2024-12-12 Cong Chen , Mo Huang , Xuekui Zhang

In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…

Systems and Control · Electrical Eng. & Systems 2022-05-17 Mazen Alamir

Model-assisted designs have garnered significant attention in recent years due to their high accuracy in identifying the maximum tolerated dose (MTD) and their operational simplicity. To identify the MTD, they employ estimated dose limiting…

Applications · Statistics 2025-08-19 Rentaro Wakayama , Tomotaka Momozaki , Shuji Ando

Sequential trial design is an important statistical approach to increase the efficiency of clinical trials. Bayesian sequential trial design relies primarily on conducting a Monte Carlo simulation under the hypotheses of interest and…

Methodology · Statistics 2025-12-01 Riko Kelter , Samuel Pawel

The development of targeted therapies, which benefit only a subgroup of patients treated for a given type of cancer, has been extremely attractive to many investigators. Adaptive seamless phase II/III designs in oncology clinical trials…

Applications · Statistics 2016-03-08 Ryuji Uozumi , Chikuma Hamada

Glioblastoma is profoundly heterogeneous in microstructure and vasculature, which may lead to tumor regional diversity and distinct treatment response. Although successful in tumor sub-region segmentation and survival prediction, radiomics…

Image and Video Processing · Electrical Eng. & Systems 2021-09-30 Yifan Li , Chao Li , Stephen Price , Carola-Bibiane Schönlieb , Xi Chen

A treatment regime is a deterministic function that dictates personalized treatment based on patients' individual prognostic information. There is a fast-growing interest in finding optimal treatment regimes to maximize expected long-term…

Statistics Theory · Mathematics 2016-11-25 Runchao Jiang , Wenbin Lu , Rui Song , Marie Davidian

Understanding treatment effect heterogeneity has become an increasingly popular task in various fields, as it helps design personalized advertisements in e-commerce or targeted treatment in biomedical studies. However, most of the existing…

Methodology · Statistics 2024-07-12 Waverly Wei , Xinwei Ma , Jingshen Wang

In randomized controlled trials (RCTs) of infectious disease interventions, it is well recognized that unmeasured individual heterogeneity at baseline can induce selection bias over time, thereby complicating the interpretation of the…

Methodology · Statistics 2026-04-24 Hiroyasu Ando , A. James O'Malley , Akihiro Nishi

Dose-finding clinical trials in oncology aim to determine the maximum tolerated dose (MTD) of a new drug, generally defined by the proportion of patients with short-term dose-limiting toxicities (DLTs). Model-based approaches for such phase…

Methodology · Statistics 2020-12-08 Moreno Ursino , Lucie Biard , Sylvie Chevret

Multi-arm trials are gaining interest in practice given the statistical and logistical advantages they can offer. The standard approach uses a fixed allocation ratio, but there is a call for making it adaptive and skewing the allocation of…

Methodology · Statistics 2026-01-16 Gianmarco Caruso , Pavel Mozgunov

We propose a novel adaptive design for clinical trials with time-to-event outcomes and covariates (which may consist of or include biomarkers). Our method is based on the expected entropy of the posterior distribution of a proportional…

Applications · Statistics 2016-03-29 James E. Barrett

Precision medicine tailors treatments to individual patient characteristics, which is especially valuable for conditions like obstructive sleep apnea (OSA), where treatment responses vary widely. Traditional trials often overlook subgroup…

Applications · Statistics 2025-03-20 Lara Maleyeff , Shirin Golchi , Erica E. M. Moodie , R. John Kimoff

With an increasing focus on precision medicine in medical research, numerous studies have been conducted in recent years to clarify the relationship between treatment effects and patient characteristics. The treatment effects for patients…

Methodology · Statistics 2023-09-22 Ke Wan , Kensuke Tanioka , Toshio Shimokawa

Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…

Objective: To compare different risk-based methods for optimal prediction of treatment effects. Methods: We simulated RCT data using diverse assumptions for the average treatment effect, a baseline prognostic index of risk (PI), the shape…

Estimating varying treatment effects in randomized trials with noncompliance is inherently challenging since variation comes from two separate sources: variation in the impact itself and variation in the compliance rate. In this setting,…

Applications · Statistics 2024-08-28 Jared D. Fisher , David W. Puelz , Sameer K. Deshpande