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Statistical methodology for the design and analysis of clinical Phase II dose response studies, with related software implementation, are well developed for the case of a normally distributed, homoscedastic response considered for a single…

Methodology · Statistics 2014-05-09 José Pinheiro , Björn Bornkamp , Ekkehard Glimm , Frank Bretz

Successful pharmaceutical drug development requires finding correct doses that provide an optimum balance between efficacy and toxicity. Competing responses to dose such as efficacy and toxicity often will increase with dose, and it is…

Applications · Statistics 2024-01-26 A. Lawrence Gould

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

In a Phase II dose-finding study with a placebo control, a new drug with several dose levels is compared with a placebo to test for the effectiveness of the new drug. The main focus of such studies often lies in the characterization of the…

Methodology · Statistics 2020-07-14 Saswati Saha , Werner Brannath

Agent-based simulation with a synthetic population can help us compare different treatment conditions while keeping everything else constant within the same population (i.e., as digital twins). Such population-scale simulations require…

Methodology · Statistics 2024-03-26 Abdulrahman A. Ahmed , M. Amin Rahimian , Mark S. Roberts

Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…

Computation · Statistics 2025-03-11 Michael Sweeting , Daniel Slade , Dan Jackson , Kristian Brock

Traditionally model averaging has been viewed as an alternative to model selection with the ultimate goal to incorporate the uncertainty associated with the model selection process in standard errors and confidence intervals by using a…

Methodology · Statistics 2021-03-05 Michael Schomaker , Christian Heumann

A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in…

Statistics Theory · Mathematics 2016-03-16 Chrystel Feller , Kirsten Schorning , Holger Dette , Georgina Bermann , Björn Bornkamp

Model averaging is a useful and robust method for dealing with model uncertainty in statistical analysis. Often, it is useful to consider data subset selection at the same time, in which model selection criteria are used to compare models…

Methodology · Statistics 2023-10-26 Ethan T. Neil , Jacob W. Sitison

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

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

Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…

Applications · Statistics 2024-04-03 Cheng-Han Yang , Peter F. Thall , Ruitao Lin

In this paper we briefly review the main methodological aspects concerned with the application of the Bayesian approach to model choice and model averaging in the context of variable selection in regression models. This includes prior…

Computation · Statistics 2016-12-08 Anabel Forte , Gonzalo Garcia-Donato , Mark Steel

We consider two problems that are attracting increasing attention in clinical dose finding studies. First, we assess the similarity of two non-linear regression models for two non-overlapping subgroups of patients over a restricted…

Methodology · Statistics 2017-09-12 Frank Bretz , Kathrin Möllenhoff , Holger Dette , Wei Liu , Matthias Trampisch

In the era of big data, analysts usually explore various statistical models or machine learning methods for observed data in order to facilitate scientific discoveries or gain predictive power. Whatever data and fitting procedures are…

Machine Learning · Statistics 2018-10-24 Jie Ding , Vahid Tarokh , Yuhong Yang

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…

Effects of the averaging over disorder realizations (samples) on the phase behavior are analyzed in terms of the mean field approximation for the random field Ising model with infinite range interactions. It is found that the averaging is…

Statistical Mechanics · Physics 2013-12-03 E. V. Vakarin , W. Dong , J. P. Badiali

In statistical exercises where there are several candidate models, the traditional approach is to select one model using some data driven criterion and use that model for estimation, testing and other purposes, ignoring the variability of…

Statistics Theory · Mathematics 2008-12-18 Snigdhansu Chatterjee , Nitai D. Mukhopadhyay

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

Background: Any sample of individuals has its own, unique distribution of preferences for choices that they make. Discrete choice models try to capture these distributions. Mixed logits are by far the most commonly used choice model in…

Econometrics · Economics 2025-06-18 John Buckell , Alice Wreford , Matthew Quaife , Thomas O. Hancock
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