A Simulation Study to Compare New Adaptive Dose-Ranging Designs

被引：47

作者：

Dragalin, Vladimir ^{[1
]}

Bornkamp, Bjoern ^{[2
]}

Bretz, Frank ^{[3
]}

Miller, Frank ^{[4
]}

Padmanabhan, S. Krishna ^{[5
]}

Patel, Nitin ^{[6
]}

Perevozskaya, Inna ^{[7
]}

Pinheiro, Jose ^{[8
]}

Smith, Jonathan R. ^{[9
]}

机构：

[1] Ctr Stat Drug Dev, Morrisville, NC 27560 USA

[2] TU Dortmund Univ, Dortmund, Germany

[3] Novartis Pharma AG, Stat Methodol Grp, Basel, Switzerland

[4] AstraZeneca, Sodertjalje, Sweden

[5] Pfizer, SRCC, Collegeville, PA USA

[6] Cytel, Cambridge, MA USA

[7] Pfizer, Biometr, Collegeville, PA USA

[8] Johnson & Johnson, PRD, Raritan, NJ USA

[9] Adapt Plus LLC, Durham, NC USA

来源：

STATISTICS IN BIOPHARMACEUTICAL RESEARCH | 2010年 / 2卷 / 04期

关键词：

Adaptive allocation; Adaptive clinical trial; Dose-finding; Dose-ranging; Dose-response; Minimum effective dose; Phase II; Response-adaptive allocation; Target dose; PHRMA WORKING GROUP; REGRESSION-MODELS; WHITE PAPER; TRIALS;

D O I：

10.1198/sbr.2010.09045

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The main goals in an adaptive dose-ranging study are to detect dose response, to determine if any doses(s) meets clinical relevance, to estimate the dose-response, and then to decide on the dose(s) (if any) to take into the confirmatory Phase III. Adaptive dose-ranging study designs may result in power gains to detect dose response and higher precision in estimating the target dose and the dose response curve. In this article, we complement the library of available methods with five new adaptive dose-ranging designs. Due to their inherent complexity, the operating characteristics can be assessed only through intensive simulations. We present here results of a comprehensive simulation study that compares and contrasts these designs for a variety of different scenarios.

引用

页码：487 / 512

页数：26

共 26 条

[1] Impact of Dose Selection Strategies Used in Phase II on the Probability of Success in Phase III [J].