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Over time, clinical trials have increasingly incorporated complex design and analysis elements such as interim analyses, adaptations, multiple endpoints, and sophisticated multiplicity schemes for multiple endpoints and/or treatment arms…

Randomized clinical trials are the gold standard when estimating the average treatment effect. However, they are usually not a random sample from the real-world population because of the inclusion/exclusion rules. Meanwhile, observational…

Methodology · Statistics 2024-12-11 Kuan Jiang , Wenjie Hu , Shu Yang , Xinxing Lai , Xiaohua Zhou

Background: Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without…

Clinical language processing has received a lot of attention in recent years, resulting in new models or methods for disease phenotyping, mortality prediction, and other tasks. Unfortunately, many of these approaches are tested under…

Computation and Language · Computer Science 2022-09-30 Travis R. Goodwin , Dina Demner-Fushman

Clinical trial outcome prediction seeks to estimate the likelihood that a clinical trial will successfully reach its intended endpoint. This process predominantly involves the development of machine learning models that utilize a variety of…

Biomolecules · Quantitative Biology 2024-05-14 Chufan Gao , Tianfan Fu , Jimeng Sun

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

A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to…

Statistics Theory · Mathematics 2011-05-25 Jay Bartroff , Tze Leung Lai

Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical and efficient. These benefits are achieved while preserving the integrity and validity of the…

Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. The main goal is to make the process of introducing new medical interventions to patients more efficient by reducing the cost and the…

Machine Learning · Computer Science 2014-11-17 Ognjen Arandjelovic

In randomized clinical trials, adjustments for baseline covariates at both design and analysis stages are highly encouraged by regulatory agencies. A recent trend is to use a model-assisted approach for covariate adjustment to gain…

Methodology · Statistics 2021-07-14 Ting Ye , Jun Shao , Yanyao Yi , Qingyuan Zhao

In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is…

Recent FDA guidance on adaptive clinical trial designs defines bias as "a systematic tendency for the estimate of treatment effect to deviate from its true value", and states that it is desirable to obtain and report estimates of treatment…

The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a…

Other Quantitative Biology · Quantitative Biology 2023-04-17 Steven Sun , Hans-Jochen Weber , Emily Butler , Kaspar Rufibach , Satrajit Roychoudhury

A prediction interval covers a future observation from a random process in repeated sampling, and is typically constructed by identifying a pivotal quantity that is also an ancillary statistic. Analogously, a tolerance interval covers a…

Methodology · Statistics 2022-01-19 Geoffrey S Johnson

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

In this study, we present a novel clinical decision support system and discuss its interpretability-related properties. It combines a decision set of rules with a machine learning scheme to offer global and local interpretability. More…

Methodology · Statistics 2021-07-16 Francisco Valente , Simão Paredes , Jorge Henriques

Classification is a common statistical task in many areas. In order to ameliorate the performance of the existing methods, there are always some new classification procedures proposed. These procedures, especially those raised in the…

Methodology · Statistics 2026-05-05 Yuan-chin Ivan Chang

Randomized controlled trials (RCTs) often suffer from limited inferential efficiency in estimating treatment effects due to their small sample sizes. In recent years, incorporating external controls (ECs) has gained increasing attention as…

Methodology · Statistics 2026-04-16 Qinwei Yang , Jingyi Li , Peng Wu , Shu Yang

The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…

Methodology · Statistics 2024-10-29 Thomas Burnett , Thomas Jaki

The most dangerous error in clinical trial interpretation is equating p > 0.05 with no effect. This review provides a practical, algorithm-based framework for classifying randomized controlled trial (RCT) results into six distinct…

Methodology · Statistics 2026-04-13 Ibrahim Halil Tanboga
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