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For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…

Methodology · Statistics 2018-06-19 Pavel Mozgunov , Thomas Jaki

Complex biological processes are usually experimented along time among a collection of individuals. Longitudinal data are then available and the statistical challenge is to better understand the underlying biological mechanisms. The…

Statistics Theory · Mathematics 2015-06-11 Pierre Barbillon , Célia Barthélémy , Adeline Samson

Background: Pairwise and network meta-analyses using fixed effect and random effects models are commonly applied to synthesise evidence from randomised controlled trials. The models differ in their assumptions and the interpretation of the…

Methodology · Statistics 2017-08-04 Shijie Ren , Jeremy E. Oakley , John W. Stevens

Diagnostic test accuracy studies typically report the number of true positives, false positives, true negatives and false negatives. There usually exists a negative association between the number of true positives and true negatives,…

Methodology · Statistics 2015-11-06 Aristidis K. Nikoloulopoulos

Weighted estimators are commonly used for estimating exposure effects in observational settings to establish causal relations. These estimators have a long history of development when the exposure of interest is binary and where the weights…

An important tool to evaluate the performance of any design is an optimal benchmark proposed by O'Quigley and others (2002, Biostatistics 3(1), 51-56) that provides an upper bound on the performance of a design under a given scenario. The…

Statistics Theory · Mathematics 2018-03-06 Pavel Mozgunov , Thomas Jaki , Xavier Paoletti

Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…

Methodology · Statistics 2013-09-20 Suyu Liu , Ying Yuan

For many decades now, Bayesian Model Averaging (BMA) has been a popular framework to systematically account for model uncertainty that arises in situations when multiple competing models are available to describe the same or similar…

Computation · Statistics 2022-03-29 Vojtech Kejzlar , Shrijita Bhattacharya , Mookyong Son , Tapabrata Maiti

Bivariate meta-analysis provides a useful framework for combining information across related studies and has been utilised to combine evidence from clinical studies to evaluate treatment efficacy on two outcomes. It has also been used to…

Applications · Statistics 2022-05-20 Tasos Papanikos , John R Thompson , Keith R Abrams , Sylwia Bujkiewicz

Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…

For nearly any challenging scientific problem evaluation of the likelihood is problematic if not impossible. Approximate Bayesian computation (ABC) allows us to employ the whole Bayesian formalism to problems where we can use simulations…

Computation · Statistics 2011-07-04 Chris Barnes , Sarah Filippi , Michael P. H. Stumpf , Thomas Thorne

We revisit the classical, full-fledged Bayesian model averaging (BMA) paradigm to ensemble pre-trained and/or lightly-finetuned foundation models to enhance the classification performance on image and text data. To make BMA tractable under…

Machine Learning · Computer Science 2025-05-29 Mijung Park

Subgroup analysis is a frequently used tool for evaluating heterogeneity of treatment effect and heterogeneity in treatment harm across observed baseline patient characteristics. While treatment efficacy and adverse event measures are often…

Applications · Statistics 2018-08-14 Nicholas C. Henderson , Ravi Varadhan

Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…

Methodology · Statistics 2022-09-13 Christian Röver , Moreno Ursino , Tim Friede , Sarah Zohar

Biopharmaceutical manufacturing is a rapidly growing industry with impact in virtually all branches of medicines. Biomanufacturing processes require close monitoring and control, in the presence of complex bioprocess dynamics with many…

Artificial Intelligence · Computer Science 2022-07-26 Hua Zheng , Wei Xie , Ilya O. Ryzhov , Dongming Xie

Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete…

Many drugs used therapeutically or recreationally induce tolerance: the effect of the substance decreases with repeated use. This phenomenon may reduce the efficacy of the substance unless dosage is increased beyond what is healthy for the…

Dynamical Systems · Mathematics 2024-03-19 Golrokh Nouri , Paul Tupper

Randomized clinical trials are considered the gold standard for estimating causal effects. Nevertheless, in studies that are aimed at examining adverse effects of interventions, such trials are often impractical because of ethical and…

Methodology · Statistics 2020-01-20 Anthony D. Scotina , Andrew R. Zullo , Robert J. Smith , Roee Gutman

Phase I dose-finding studies aim at identifying the maximal tolerated dose (MTD). It is not uncommon that several dose-finding studies are conducted, although often with some variation in the administration mode or dose panel. For instance,…

Quantitative Methods · Quantitative Biology 2021-03-24 Moreno Ursino , Christian Röver , Sarah Zohar , Tim Friede

Clinical trials often aim to compare a new drug with a reference treatment in terms of efficacy and/or toxicity depending on covariates such as, for example, the dose level of the drug. Equivalence of these treatments can be claimed if the…

Methodology · Statistics 2019-10-22 Holger Dette , Kathrin Möllenhoff , Frank Bretz