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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Pharmaceutical Stati...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Pharmaceutical Statistics
Article . 2024 . Peer-reviewed
License: Wiley Online Library User Agreement
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Reparametrized Firth's Logistic Regressions for Dose‐Finding Study With the Biased‐Coin Design

Authors: Hyungwoo Kim; Seungpil Jung; Yudi Pawitan; Woojoo Lee;

Reparametrized Firth's Logistic Regressions for Dose‐Finding Study With the Biased‐Coin Design

Abstract

ABSTRACTFinding an adequate dose of the drug by revealing the dose–response relationship is very crucial and a challenging problem in the clinical development. The main concerns in dose‐finding study are to identify a minimum effective dose (MED) in anesthesia studies and maximum tolerated dose (MTD) in oncology clinical trials. For the estimation of MED and MTD, we propose two modifications of Firth's logistic regression using reparametrization, called reparametrized Firth's logistic regression (rFLR) and ridge‐penalized reparametrized Firth's logistic regression (RrFLR). The proposed methods are designed by directly reducing the small‐sample bias of the maximum likelihood estimate for the parameter of interest. In addition, we develop a method on how to construct confidence intervals for rFLR and RrFLR using profile penalized likelihood. In the up‐and‐down biased‐coin design, numerical studies confirm the superior performance of the proposed methods in terms of the mean squared error, bias, and coverage accuracy of confidence intervals.

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Keywords

Likelihood Functions, Logistic Models, Maximum Tolerated Dose, Dose-Response Relationship, Drug, Bias, Research Design, Confidence Intervals, Humans, Computer Simulation

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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