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Stepped wedge cluster randomized trials (SWCRTs) often face challenges with potential confounding by time trends. Traditional frequentist methods can fail to provide adequate coverage of the intervention's true effect using confidence…

Methodology · Statistics 2024-02-02 Danni Wu , Hyung G. Park , Corita R. Grudzen , Keith S. Goldfeld

Dynamic treatment regimes in oncology and other disease areas often can be characterized by an alternating sequence of treatments or other actions and transition times between disease states. The sequence of transition states may vary…

Applications · Statistics 2015-11-17 Yanxun Xu , Peter Mueller , Abdus S. Wahed , Peter F. Thall

Bayesian experimental design (BED) is a framework that uses statistical models and decision making under uncertainty to optimise the cost and performance of a scientific experiment. Sequential BED, as opposed to static BED, considers the…

Machine Learning · Statistics 2020-03-23 Steven Kleinegesse , Christopher Drovandi , Michael U. Gutmann

This paper presents TimelinePTC, a web-based tool developed to improve the collection and analysis of Pathways to Care (PTC) data in first episode psychosis (FEP) research. Accurately measuring the duration of untreated psychosis (DUP) is…

Human-Computer Interaction · Computer Science 2024-04-22 Walter S. Mathis , Maria Ferrara , John Cahill , Sneha Karmani , Sümeyra N. Tayfur , Vinod Srihari

Current Targeted Maximum Likelihood Estimation (TMLE) methods used to analyze time-to-event data estimate the survival probability for each time point separately, which result in estimates that are not necessarily monotone. In this paper,…

Methodology · Statistics 2019-06-14 Weixin Cai , Mark J. van der Laan

In this paper, the recurrent events that can occur more than one over the follow-up time have been modeled by phase-type distributions. We use the finite-state continuous-time Markov process with multi states for patients with recurrent…

Methodology · Statistics 2022-01-26 Roufeh Asghari , Amin Hassan Zadeh

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

Real-world evidence (RWE) studies that emulate target trials increasingly inform regulatory and clinical decisions, yet residual, hard-to-quantify biases still limit their credibility. The recently proposed BenchExCal framework addresses…

Artificial Intelligence · Computer Science 2026-04-29 Amir Habibdoust , Xing Song

Artificial intelligence (AI) is increasingly used in every stage of drug development. One challenge facing drug discovery AI is that drug pharmacokinetic (PK) datasets are often collected independently from each other, often with limited…

Quantitative Methods · Quantitative Biology 2025-07-03 Bing Hu , Anita Layton , Helen Chen

Pharmacokinetic modeling using ordinary differential equations (ODEs) has an important role in dose optimization studies, where dosing must balance sustained therapeutic efficacy with the risk of adverse side effects. Such ODE models…

Methodology · Statistics 2025-06-30 Yuxuan Zhao , Samuel W. K. Wong

Powerful array-based single-nucleotide polymorphism--typing platforms have recently heralded a new era in which genome-wide studies are conducted with increasing frequency. A genetic polymorphism associated with population pharmacokinetics…

Methodology · Statistics 2018-05-15 Kengo Nagashima , Yasunori Sato , Hisashi Noma , Chikuma Hamada

Recently, numerous pharmaceutical sponsors have expressed a great deal of interest in the development of biosimilars, which requires clinical trials to demonstrate the equivalence of pharmacokinetics (PK) and clinical efficacy.…

Applications · Statistics 2017-05-16 Ryuji Uozumi , Chikuma Hamada

In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…

Methodology · Statistics 2026-05-07 Yuxuan Chen , Haiming Zhou , Keiko Nakajima , Philip He

Randomised controlled trials (RCTs) are regarded as the gold standard for estimating causal treatment effects on health outcomes. However, RCTs are not always feasible, because of time, budget or ethical constraints. Observational data such…

Methodology · Statistics 2024-02-20 Li Su , Roonak Rezvani , Shaun R. Seaman , Colin Starr , Isaac Gravestock

In many clinical trials treatments need to be repeatedly applied as diseases relapse frequently after remission over a long period of time (e.g., 35 weeks). Most research in statistics focuses on the overall trial design, such as sample…

Methodology · Statistics 2014-04-01 Yanxun Xu , Yuan Ji

Likelihood methods for measuring statistical evidence obey the likelihood principle while maintaining bounded and well-controlled frequency properties. These methods lend themselves to sequential study designs because they measure the…

Methodology · Statistics 2017-11-07 Jeffrey D Blume , Leena Choi

We review methods for monitoring multivariate time-between-events (TBE) data. We present some underlying complexities that have been overlooked in the literature. It is helpful to classify multivariate TBE monitoring applications into two…

Applications · Statistics 2019-11-06 Inez Maria Zwetsloot , Tahir Mahmood , William H. Woodall

The effects of molecularly targeted drug perturbations on cellular activities and fates are difficult to predict using intuition alone because of the complex behaviors of cellular regulatory networks. An approach to overcoming this problem…

Systems and Control · Computer Science 2019-01-15 Afroza Shirin , Isaac Klickstein , Song Feng , Yen Ting Lin , William S. Hlavacek , Francesco Sorrentino

We propose a multi-metric flexible Bayesian framework to support efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Multi-arm multi-stage phase II studies increase the efficiency of drug development, but…

Applications · Statistics 2023-12-15 Suzanne M. Dufault , Angela M. Crook , Katie Rolfe , Patrick P. J. Phillips

The analysis of data from multiple experiments, such as observations of several individuals, is commonly approached using mixed-effects models, which account for variation between individuals through hierarchical representations. This makes…

Computation · Statistics 2026-03-05 Henrik Häggström , Sebastian Persson , Marija Cvijovic , Umberto Picchini