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A randomized trial allows estimation of the causal effect of an intervention compared to a control in the overall population and in subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding…

Nonlinear causal effects are prevalent in many research scenarios involving continuous exposures, and instrumental variables (IVs) can be employed to investigate such effects, particularly in the presence of unmeasured confounders. However,…

Methodology · Statistics 2025-10-29 Haodong Tian , Ashish Patel , Stephen Burgess

An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…

Methodology · Statistics 2018-11-27 Marius Thomas , Björn Bornkamp , Katja Ickstadt

This paper deals with the concept of equivalence between direct and indirect effects of a treatment on a response using two sets of intermediate variables and covariates. First, we provide criteria for testing whether two sets of variables…

Statistics Theory · Mathematics 2016-01-07 Manabu Kuroki

The external validity of regression discontinuity designs is crucial for informing policy but is rarely examined in applied work. To advance empirical practice, we propose a joint inference procedure for the treatment effect and its local…

Econometrics · Economics 2026-02-17 Yuta Okamoto

Background: Clinical trials rely on transparent inclusion criteria to ensure generalizability. In contrast, benchmarks validating health-related large language models (LLMs) rarely characterize the "patient" or "query" populations they…

Artificial Intelligence · Computer Science 2026-04-17 Alvin Rajkomar , Pavan Sudarshan , Angela Lai , Lily Peng

Competing risks data arise frequently in clinical trials. When the proportional subdistribution hazard assumption is violated or two cumulative incidence function (CIF) curves cross, rather than comparing the overall treatment effects,…

Applications · Statistics 2021-06-22 Jinbao Chen , Yawen Hou , Zheng Chen

Background: Children are frequently prescribed medication off-label, meaning there has not been sufficient testing of the medication to determine its safety or effectiveness. The main reason this safety knowledge is lacking is due to…

Machine Learning · Computer Science 2014-09-03 Jenna M. Reps , Jonathan M. Garibaldi , Uwe Aickelin , Daniele Soria , Jack E. Gibson , Richard B. Hubbard

Multivariate equivalence testing is needed in a variety of scenarios for drug development. For example, drug products obtained from natural sources may contain many components for which the individual effects and/or their interactions on…

Methodology · Statistics 2024-06-07 Chao Wang , Yu-Ting Weng , Shaobo Liu , Tengfei Li , Meiyu Shen , Yi Tsong

Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two-stage network meta-regression prediction model that synthesized randomized trials and evaluates how treatment…

Many deployments must compare candidate language models for safety before a labeled benchmark exists for the relevant language, sector, or regulatory regime. We formalize this setting as benchmarkless comparative safety scoring and specify…

The method of instrumental variables provides a fundamental and practical tool for causal inference in many empirical studies where unmeasured confounding between the treatments and the outcome is present. Modern data such as the genetical…

Methodology · Statistics 2022-10-28 Ziang Niu , Yuwen Gu , Wei Li

Interim analyses for group-sequential decision making are prevalent in clinical trials. Methodology is well established and has been routinely implemented over the last decades. Still, confusions and uncertainties on aspects of how to…

We derive the sample size formulae for comparing two negative binomial rates based on both the relative and absolute rate difference metrics in noninferiority and equivalence trials with unequal follow-up times, and establish an approximate…

Methodology · Statistics 2017-05-24 Yongqiang Tang

Historical prescriptions and selected candidate drugs relevant to the current visit serve as important references for medication recommendation. However, in the absence of explicit intrinsic principles for semantic composition, existing…

Computational Engineering, Finance, and Science · Computer Science 2026-01-28 Yanda Wang , Weitong Chen , Chao Tan , Ian Nabney , Lin Yue , Genlin Ji

Detecting complex interactions among risk factors in case-control studies is a fundamental task in clinical and population research. However, though hypothesis testing using logistic regression (LR) is a convenient solution, the LR…

Methodology · Statistics 2015-02-11 Guoqiang Yu , David J. Miller , Carl D. Langefeld , David M. Herrington , Yue Wang

External validation is often recommended to ensure the generalizability of ML models. However, it neither guarantees generalizability nor equates to a model's clinical usefulness (the ultimate goal of any clinical decision-support tool).…

Machine Learning · Computer Science 2023-05-16 Alex Youssef , Michael Pencina , Anshul Thakur , Tingting Zhu , David Clifton , Nigam H. Shah

We consider the problem of indirect comparison, where a treatment arm of interest is absent by design in one randomized controlled trial but available in the other. The former is the target trial, and the latter is the source trial. The…

Methodology · Statistics 2025-06-06 Zehao Su , Helene C. W. Rytgaard , Henrik Ravn , Frank Eriksson

Estimating the impact of continuous treatment variables (e.g., dosage amount) on binary outcomes presents significant challenges in modeling and estimation because many existing approaches make strong assumptions that do not hold for…

Methodology · Statistics 2025-05-08 Muyan Jiang , Yunkai Zhang , Anil Aswani

Estimating treatment effects from observational data is of central interest across numerous application domains. Individual treatment effect offers the most granular measure of treatment effect on an individual level, and is the most useful…

Machine Learning · Statistics 2024-08-06 Hengrui Cai , Huaqing Jin , Lexin Li