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Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…

Methodology · Statistics 2018-08-23 Jose L. Jimenez , Mourad Tighiouart , Mauro Gasparini

Conformal prediction has emerged as a popular technique for facilitating valid predictive inference across a spectrum of machine learning models, under minimal assumption of exchangeability. Recently, Hoff (2023) showed that full conformal…

Statistics Theory · Mathematics 2025-11-24 Pankaj Bhagwat , Linglong Kong , Bei Jiang

Phase II dose finding studies in clinical drug development are typically conducted to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to…

Applications · Statistics 2015-08-04 Kirsten Schorning , Björn Bornkamp , Frank Bretz , Holger Dette

An important objective in biomedical risk assessment is estimation of minimum exposure levels that induce a pre-specified adverse response in a target population. The exposure/dose points in such settings are known as Benchmark Doses…

Methodology · Statistics 2014-02-18 Qijun Fang , Walter W. Piegorsch , Susan J. Simmons , Xiaosong Li , Cuixian Chen , Yishi Wang

Dose-finding studies are frequently conducted to evaluate the effect of different doses or concentration levels of a compound on a response of interest. Applications include the investigation of a new medicinal drug, a herbicide or…

Applications · Statistics 2011-08-01 Björn Bornkamp , Frank Bretz , Holger Dette , José Pinheiro

For many cancer sites low-dose risks are not known and must be extrapolated from those observed in groups exposed at much higher levels of dose. Measurement error can substantially alter the dose-response shape and hence the extrapolated…

Quantitative Methods · Quantitative Biology 2024-03-15 Mark P Little , Nobuyuki Hamada , Lydia B Zablotska

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

Applications · Statistics 2011-08-09 Ying Yuan , Guosheng Yin

This paper describes several approaches for estimating the benchmark dose (BMD) in a risk assessment study with quantal dose-response data and when there are competing model classes for the dose-response function. Strategies involving a…

Statistics Theory · Mathematics 2019-11-19 Edsel A. Pena , Wensong Wu , Walter Piegorsch , Ronald W. West , Lingling An

Most conventional risk analysis methods rely on a single best estimate of exposure per person which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the…

Applications · Statistics 2020-04-07 Deukwoo Kwon , F. Owen Hoffman , Brian E. Moroz , Steven L. Simon

Autonomous Experimentation Platforms (AEPs) are advanced manufacturing platforms that, under intelligent control, can sequentially search the material design space (MDS) and identify parameters with the desired properties. At the heart of…

Machine Learning · Computer Science 2023-02-28 Ahmed Shoyeb Raihan , Imtiaz Ahmed

Phase I clinical trials are essential to bringing novel therapies from chemical development to widespread use. Traditional approaches to dose-finding in Phase I trials, such as the '3+3' method and the Continual Reassessment Method (CRM),…

Methodology · Statistics 2024-03-04 Luka Kovacevic , Thomas Jaki , Helen Barnett , Pavel Mozgunov

Dose-response models express the effect of different dose or exposure levels on a specific outcome. In meta-analysis, where aggregated-level data is available, dose-response evidence is synthesized using either one-stage or two-stage models…

The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…

Methodology · Statistics 2017-11-16 Kirsten Schorning , Maria Konstantinou

Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…

Determining the extent to which a patient is benefiting from cancer therapy is challenging. Criteria for quantifying the extent of "tumor response" observed within a few cycles of treatment have been established for various types of solid…

Methodology · Statistics 2020-09-18 Jie Zhou , Xun Jiang , H. Amy Xia , Peng Wei , Brian P. Hobbs

We propose Bayesian model averaging (BMA) as a method for postprocessing the results of model-based clustering. Given a number of competing models, appropriate model summaries are averaged, using the posterior model probabilities, instead…

Computation · Statistics 2015-07-01 Niamh Russell , Thomas Brendan Murphy , Adrian E Raftery

Model-assisted designs have garnered significant attention in recent years due to their high accuracy in identifying the maximum tolerated dose (MTD) and their operational simplicity. To identify the MTD, they employ estimated dose limiting…

Applications · Statistics 2025-08-19 Rentaro Wakayama , Tomotaka Momozaki , Shuji Ando

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

Benchmark dose (BMD; a dose associated with a specified change in response) is used to determine the point of departure for the acceptable daily intake of substances for humans. Multiple dose-response relationship models are considered in…

Computation · Statistics 2025-05-13 Sota Minewaki , Tomohiro Ohigashi , Takashi Sozu

A general challenge in statistics is prediction in the presence of multiple candidate models or learning algorithms. Model aggregation tries to combine all predictive distributions from individual models, which is more stable and flexible…

Methodology · Statistics 2021-09-28 Yuling Yao
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