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The use of patient-level information from previous studies, registries, and other external datasets can support the analysis of single-arm and randomized controlled trials to evaluate and test experimental treatments. However, the…

Methodology · Statistics 2025-10-23 Gopal Kotecha , Daniel E. Schwartz , Steffen Ventz , Lorenzo Trippa

Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial…

Methodology · Statistics 2022-07-13 Yanyao Yi , Ying Zhang , Yu Du , Ting Ye

Individualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials…

Estimating treatment effects conditional on observed covariates can improve the ability to tailor treatments to particular individuals. Doing so effectively requires dealing with potential confounding, and also enough data to adequately…

One approach for increasing the efficiency of randomized trials is the use of "external controls" -- individuals who received the control treatment studied in the trial during routine practice or in prior experimental studies. Existing…

The primary benefit of identifying a valid surrogate marker is the ability to use it in a future trial to test for a treatment effect with shorter follow-up time or less cost. However, previous work has demonstrated potential heterogeneity…

Methodology · Statistics 2022-09-20 Layla Parast , Tianxi Cai , Lu Tian

Subgroup analyses of randomized controlled trials (RCTs) constitute an important component of the drug development process in precision medicine. In particular, subgroup analyses of early-stage trials often influence the design and…

Methodology · Statistics 2025-02-12 Daniel Schwartz , Riddhiman Saha , Steffen Ventz , Lorenzo Trippa

Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence…

Statistics Theory · Mathematics 2020-05-28 Andrea Arfé , Brian Alexander , Lorenzo Trippa

Suppose we are interested in the effect of a treatment in a clinical trial. The efficiency of inference may be limited due to small sample size. However, external control data are often available from historical studies. Motivated by an…

Methodology · Statistics 2021-12-10 Xinyu Li , Wang Miao , Fang Lu , Xiao-Hua Zhou

Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…

Methodology · Statistics 2025-06-04 Nan Miles Xi , Man Mandy Jin , Lin Wang , Xin Huang

One size fits all approaches to medicine have become a thing of the past as the understanding of individual differences grows. The paper introduces a test for the presence of heterogeneity in treatment effects in a clinical trial.…

Every design choice will have different effects on different units. However traditional A/B tests are often underpowered to identify these heterogeneous effects. This is especially true when the set of unit-level attributes is…

Artificial Intelligence · Computer Science 2016-11-09 Alexander Peysakhovich , Akos Lada

Experimentation is widely utilized for causal inference and data-driven decision-making across disciplines. In an A/B experiment, for example, an online business randomizes two different treatments (e.g., website designs) to their customers…

Methodology · Statistics 2025-01-15 Wenxuan Guo , JungHo Lee , Panos Toulis

We propose a test-based elastic integrative analysis of the randomized trial and real-world data to estimate treatment effect heterogeneity with a vector of known effect modifiers. When the real-world data are not subject to bias, our…

Methodology · Statistics 2022-11-30 Shu Yang , Chenyin Gao , Donglin Zeng , Xiaofei Wang

In situations where it is difficult to enroll patients in randomized controlled trials, external data can improve efficiency and feasibility. In such cases, adaptive trial designs could be used to decrease enrollment in the control arm of…

Methodology · Statistics 2020-10-02 Brian D. Segal , W. Katherine Tan

I introduce a simple permutation procedure to test conventional (non-sharp) hypotheses about the effect of a binary treatment in the presence of a finite number of large, heterogeneous clusters when the treatment effect is identified by…

Econometrics · Economics 2023-02-08 Andreas Hagemann

Heterogeneous treatment effects can be very important in the analysis of randomized clinical trials. Heightened risks or enhanced benefits may exist for particular subsets of study subjects. When the heterogeneous treatment effects are…

Methodology · Statistics 2025-07-25 Richard A. Berk , Matthew Olson , Andreas Buja , Aurelie Ouss

Randomized controlled trials (RCTs) often include subgroup analyses to assess whether treatment effects vary across pre-specified patient populations. However, these analyses frequently suffer from small sample sizes which limit the power…

We propose new, optimal methods for analyzing randomized trials, when it is suspected that treatment effects may differ in two predefined subpopulations. Such sub-populations could be defined by a biomarker or risk factor measured at…

Methodology · Statistics 2016-11-26 Michael Rosenblum , Han Liu , and En-Hsu Yen

We consider the problem of testing for treatment effect heterogeneity in observational studies, and propose a nonparametric test based on multisample U-statistics. To account for potential confounders, we use reweighted data where the…

Methodology · Statistics 2021-03-30 Maozhu Dai , Weining Shen , Hal S. Stern
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