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Randomized clinical trials are often designed to assess whether a test treatment prolongs survival relative to a control treatment. Increased patient heterogeneity, while desirable for generalizability of results, can weaken the ability of…

Methodology · Statistics 2020-04-30 Devan V. Mehrotra , Rachel Marceau West

The ability to generalize experimental results from randomized control trials (RCTs) across locations is crucial for informing policy decisions in targeted regions. Such generalization is often hindered by the lack of identifiability due to…

Econometrics · Economics 2021-12-10 Xinkun Nie , Guido Imbens , Stefan Wager

Amidst rising appreciation for privacy and data usage rights, researchers have increasingly acknowledged the principle of data minimization, which holds that the accessibility, collection, and retention of subjects' data should be kept to…

Cryptography and Security · Computer Science 2021-10-22 Winston Chou

Health economic evaluations face the issues of non-compliance and missing data. Here, non-compliance is defined as non-adherence to a specific treatment, and occurs within randomised controlled trials (RCTs) when participants depart from…

Applications · Statistics 2019-02-26 Karla DiazOrdaz , Richard Grieve

In this review, we present econometric and statistical methods for analyzing randomized experiments. For basic experiments we stress randomization-based inference as opposed to sampling-based inference. In randomization-based inference,…

Methodology · Statistics 2017-10-26 Susan Athey , Guido Imbens

What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has…

Methodology · Statistics 2023-04-18 José L. Jiménez , Isobel Barrott , Francesca Gasperoni , Dominic Magirr

In oncology the efficacy of novel therapeutics often differs across patient subgroups, and these variations are difficult to predict during the initial phases of the drug development process. The relation between the power of randomized…

Methodology · Statistics 2025-06-05 Boyu Ren , Federico Ferrari , Sandra Fortini , Steffen Ventz , Lorenzo Trippa

Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…

Methodology · Statistics 2020-07-09 Alexander M. Kaizer , Joseph S. Koopmeiners , Nan Chen , Brian P. Hobbs

Combining test statistics from independent trials or experiments is a popular method of meta-analysis. However, there is very limited theoretical understanding of the power of the combined test, especially in high-dimensional models…

Statistics Theory · Mathematics 2023-10-31 Botond Szabó , Aad van der Vaart , Lasse Vuursteen , Harry van Zanten

The availability of electronic health records (EHR) has opened opportunities to supplement increasingly expensive and difficult to carry out randomized controlled trials (RCT) with evidence from readily available real world data. In this…

Methodology · Statistics 2023-05-09 Noirrit Kiran Chandra , Abhra Sarkar , John F. de Groot , Ying Yuan , Peter Müller

When treating depression, clinicians are interested in determining the optimal treatment for a given patient, which is challenging given the amount of treatments available. To advance individualized treatment allocation, integrating data…

Cluster-level dynamic treatment regimens can be used to guide sequential, intervention or treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level DTR, the…

Methodology · Statistics 2016-07-15 Timothy NeCamp , Amy Kilbourne , Daniel Almirall

When a new treatment is considered for use, whether a pharmaceutical drug or a search engine ranking algorithm, a typical question that arises is, will its performance exceed that of the current treatment? The conventional way to answer…

Machine Learning · Computer Science 2016-10-27 Nir Rosenfeld , Yishay Mansour , Elad Yom-Tov

The heterogeneity of treatment effect (HTE) lies at the heart of precision medicine. Randomized controlled trials are gold-standard for treatment effect estimation but are typically underpowered for heterogeneous effects. In contrast, large…

Methodology · Statistics 2024-11-14 Shu Yang , Siyi Liu , Donglin Zeng , Xiaofei Wang

Clinical trial simulation (CTS) is critical in new drug development, providing insight into safety and efficacy while guiding trial design. Achieving realistic outcomes in CTS requires an accurately estimated joint distribution of the…

Methodology · Statistics 2025-05-08 Longwen Shang , Min Tsao , Xuekui Zhang

Clinical randomized controlled trials (RCTs) collect hundreds of measurements spanning various metric types (e.g., laboratory tests, cognitive/motor assessments, etc.) across 100s-1000s of subjects to evaluate the effect of a treatment, but…

Machine Learning · Computer Science 2024-06-25 Sayeri Lala , Niraj K. Jha

Understanding whether and how treatment effects vary across subgroups is crucial to inform clinical practice and recommendations. Accordingly, the assessment of heterogeneous treatment effects (HTE) based on pre-specified potential effect…

Methodology · Statistics 2023-12-04 Bryan S. Blette , Scott D. Halpern , Fan Li , Michael O. Harhay

While randomized trials may be the gold standard for evaluating the effectiveness of the treatment intervention, in some special circumstances, single-arm clinical trials utilizing external control may be considered. The causal treatment…

Methodology · Statistics 2025-05-26 Huan Wang , Fei Wu , Yeh-Fong Chen

Randomized controlled trials (RCTs) often exhibit limited inferential efficiency in estimating treatment effects due to small sample sizes. In recent years, the combination of external controls has gained increasing attention as a means of…

Methodology · Statistics 2025-10-06 Qinwei Yang , Jingyi Li , Peng Wu

Understanding treatment effect heterogeneity has become increasingly important in many fields. In this paper we study distributions and quantiles of individual treatment effects to provide a more comprehensive and robust understanding of…

Methodology · Statistics 2026-03-31 Zhe Chen , Xinran Li