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External controls from historical trials or observational data can augment randomized controlled trials when large-scale randomization is impractical or unethical, such as in drug evaluation for rare diseases. However, non-randomized…

Methodology · Statistics 2025-05-08 Ke Zhu , Shu Yang , Xiaofei Wang

Clinical trials are critical for drug development. Constructing the appropriate eligibility criteria (i.e., the inclusion/exclusion criteria for patient recruitment) is essential for the trial's success. Proper design of clinical trial…

Computation and Language · Computer Science 2023-10-10 Zifeng Wang , Cao Xiao , Jimeng Sun

There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a…

Applications · Statistics 2023-11-13 Jie Chen , Xiaoyun , Li , Chengxing , Lu , Sammy Yuan , Godwin Yung , Jingjing Ye , Hong Tian , Jianchang Lin

Phase III randomized clinical trials play a monumentally critical role in the evaluation of new medical products. Because of the intrinsic nature of uncertainty embedded in our capability in assessing the efficacy of a medical product,…

Methodology · Statistics 2019-02-25 Changyu Shen , Xiaochun Li

Estimating probability of failure in aerospace systems is a critical requirement for flight certification and qualification. Failure probability estimation involves resolving tails of probability distribution, and Monte Carlo sampling…

Numerical Analysis · Mathematics 2022-09-22 S. Ashwin Renganathan , Vishwas Rao , Ionel M. Navon

It is increasingly common to augment randomized controlled trial with external controls from observational data, to evaluate the treatment effect of an intervention. Traditional approaches to treatment effect estimation involve ambiguous…

Methodology · Statistics 2025-03-28 Bo Liu , Laine Thomas , Rury R. Holman , Fan Li

In adaptive clinical trials, the conventional confidence interval (CI) for a treatment effect is prone to undesirable properties such as undercoverage and potential inconsistency with the final hypothesis testing decision. Accordingly, as…

Conditional power calculations are frequently used to guide the decision whether or not to stop a trial for futility or to modify planned sample size. These ignore the information in short-term endpoints and baseline covariates, and thereby…

Methodology · Statistics 2019-04-11 Kelly Van Lancker , An Vandebosch , Stijn Vansteelandt

Externally controlled trials (ECTs) are increasingly used when randomized controls are infeasible, unethical, or insufficient, including applications in rare diseases, oncology, pediatrics, and post-approval effectiveness research. Although…

Hierarchical decision problems are often modeled as bilevel programs in which a leader commits to a policy and a follower responds optimally. When the follower's optimal response is nonunique, or when only near-optimal follower behavior can…

Optimization and Control · Mathematics 2026-05-19 Jiguang Yu

Estimating the probability of failure for expensive simulations is a central task in reliability analysis for structural design, power grid design, and safety certification, among other areas. This work derives credible intervals on the…

Methodology · Statistics 2026-03-16 Aleksei G. Sorokin , Vishwas Rao

Randomized clinical trials (RCTs) are widely considered the gold standard for evaluating the effectiveness of new treatments or interventions in drug development. Still, they may not be feasible in certain cases, such as with rare diseases…

Methodology · Statistics 2025-08-05 Di Ran , Fanni Zhang , Sima Shahsavari , Kristine Broglio , Alasdair Henderson , Binbing Yu

Assessment of replicability is critical to ensure the quality and rigor of scientific research. In this paper, we discuss inference and modeling principles for replicability assessment. Targeting distinct application scenarios, we propose…

Methodology · Statistics 2021-05-11 Yi Zhao , Xiaoquan Wen

With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials. Both industry and…

External controls (ECs) from historical trials or real-world data have gained increasing attention as a way to augment hybrid and single-arm trials, especially when balanced randomization is infeasible. While most existing work has focused…

Methodology · Statistics 2025-12-15 Yujing Gao , Xiang Zhang , Shu Yang

This paper examines how trust is formed, maintained, or diminished over time in the context of human-autonomy teaming with an optionally piloted aircraft. Whereas traditional factor-based trust models offer a static representation of human…

Human-Computer Interaction · Computer Science 2025-03-21 Jeremy C. -H. Wang , Ming Hou , David Dunwoody , Marko Ilievski , Justin Tomasi , Edward Chao , Carl Pigeon

This article discusses futility analyses for the MCP-Mod methodology. Formulas are derived for calculating predictive and conditional power for MCP-Mod, which also cover the case when longitudinal models are used allowing to utilize…

Methodology · Statistics 2024-07-01 Björn Bornkamp , Jie Zhou , Dong Xi , Weihua Cao

This paper develops a Bayesian approach for assessing equivalence and non-inferiority hypotheses in two-arm trials using relative belief ratios. A relative belief ratio is a measure of statistical evidence and can indicate evidence either…

Applications · Statistics 2014-01-20 Saman Muthukumarana , Michael Evans

Methods that address data shifts usually assume full access to multiple datasets. In the healthcare domain, however, privacy-preserving regulations as well as commercial interests limit data availability and, as a result, researchers can…

Machine Learning · Statistics 2022-05-03 Tal El-Hay , Chen Yanover

Target trial emulation has improved comparative effectiveness research by making the causal question, assumptions, and analysis plan explicit. However, target trial protocols are usually developed iteratively. After examining the data,…

Methodology · Statistics 2026-04-30 Mats Julius Stensrud