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Covariate adjustment is an approach to improve the precision of trial analyses by adjusting for baseline variables that are prognostic of the primary endpoint. Motivated by the SEARCH Universal HIV Test-and-Treat Trial (2013-2017), we tell…

Methodology · Statistics 2025-12-16 Laura B. Balzer , Mark J. van der Laan , Maya L. Petersen

Incorporating historical data or real-world evidence has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model-based designs, such as the continuous reassessment method (CRM),…

Methodology · Statistics 2020-06-11 Yanhong Zhou , J. Jack Lee , Shunguang Wang , Stuart Bailey , Ying Yuan

Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is…

Applications · Statistics 2020-01-01 Tianjian Zhou , Wentian Guo , Yuan Ji

Composite binary endpoints are increasingly used as primary endpoints in clinical trials. When designing a trial, it is crucial to determine the appropriate sample size for testing the statistical differences between treatment groups for…

Applications · Statistics 2019-01-15 Marta Bofill Roig , Guadalupe Gómez Melis

Methods to handle missing data have been extensively explored in the context of estimation and descriptive studies, with multiple imputation being the most widely used method in clinical research. However, in the context of clinical risk…

Methodology · Statistics 2024-11-25 Junhui Mi , Rahul D. Tendulkar , Sarah M. C. Sittenfeld , Sujata Patil , Emily C. Zabor

The clinical trial process, a critical phase in drug development, is essential for developing new treatments. The primary goal of interventional clinical trials is to evaluate the safety and efficacy of drug-based treatments for specific…

Machine Learning · Computer Science 2024-07-19 Ling Yue , Jonathan Li , Sixue Xing , Md Zabirul Islam , Bolun Xia , Tianfan Fu , Jintai Chen

The two-trials rule for drug approval requires "at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness". This is usually implemented by requiring two significant pivotal trials and is the…

Methodology · Statistics 2023-11-10 Leonhard Held

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient…

Computers and Society · Computer Science 2022-03-15 Tianfan Fu , Kexin Huang , Cao Xiao , Lucas M. Glass , Jimeng Sun

This paper studies the estimation and inference of treatment effects in panel data settings when treatments change dynamically over time. We propose a balancing method that allows for (i) treatments to be assigned dynamically over time…

Econometrics · Economics 2026-02-24 Davide Viviano , Jelena Bradic

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

Bayesian predictive probabilities are commonly used for interim monitoring of clinical trials through efficacy and futility stopping rules. Despite their usefulness, calculation of predictive probabilities, particularly in pre-experiment…

Applications · Statistics 2024-06-18 Joe Marion , Liz Lorenzi , Cora Allen-Savietta , Scott Berry , Kert Viele

Transitioning from Phase 2 to Phase 3 in drug development, at a rate of $\approx$40%, is the most stringent among phase transitions (Hay et al. (2014)). Yet, success rate at Phase 3 leading to approval is only $\approx$50% (Arrowsmith…

Methodology · Statistics 2025-10-29 Yujia Sun , Yang Han , Xingya Wang , Szu-Yu Tang , Yushi Liu , Jason C. Hsu

Given n experiment subjects with potentially heterogeneous covariates and two possible treatments, namely active treatment and control, this paper addresses the fundamental question of determining the optimal accuracy in estimating the…

Machine Learning · Statistics 2024-11-13 Jiachun Li , David Simchi-Levi , Yunxiao Zhao

In medical treatment and elsewhere, it has become standard to base treatment intensity (dosage) on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has…

Econometrics · Economics 2023-05-30 Charles F. Manski

Detecting predictive biomarkers from multi-omics data is important for precision medicine, to improve diagnostics of complex diseases and for better treatments. This needs substantial experimental efforts that are made difficult by the…

Quantitative Methods · Quantitative Biology 2021-06-08 Betül Güvenç Paltun , Samuel Kaski , Hiroshi Mamitsuka

Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to…

Quantitative Methods · Quantitative Biology 2023-09-19 Masahiro Kojima , Wu Wende , Henry Zhao

An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most…

Quantitative Methods · Quantitative Biology 2019-09-23 Corinna Maier , Niklas Hartung , Jana de Wiljes , Charlotte Kloft , Wilhelm Huisinga

This paper addresses the problem of deciding whether the dose response relationships between subgroups and the full population in a multi-regional trial are similar to each other. Similarity is measured in terms of the maximal deviation…

Statistics Theory · Mathematics 2024-04-30 Holger Dette , Lukas Koletzko , Frank Bretz

In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…

Methodology · Statistics 2024-05-24 Takuya Yoshimoto , Satoru Shinoda , Kouji Yamamoto , Kouji Tahata

In randomized dose-finding trials, although drug exposure data form a part of key information for dose selection, the evaluation of the dose-response (DR) relationship often mainly uses DR data. We examine the benefit of…

Methodology · Statistics 2025-08-07 Jixian Wang , Zhiwei Zhang , Ram Tiwari