Authors: Bretz, Frank
Dette, Holger
Pinheiro, Jose
Title: Practical considerations for optimal designs in clinical dose finding studies
Language (ISO): en
Abstract: Determining an adequate dose level for a drug and, more broadly, characterizing its dose response relationship, are key objectives in the clinical development of any medicinal drug. If the dose is set too high, safety and tolerability problems are likely to result, while selecting too low a dose makes it difficult to establish adequate efficacy in the confirmatory phase, possibly leading to a failed program. Hence, dose finding studies are of critical importance in drug development and need to be planned carefully. In this paper we focus on practical considerations for establishing efficient study designs to estimate target doses of interest. We consider optimal designs for both the estimation of the minimum effective dose (MED) and the dose achieving 100p% of the maximum treatment effect (EDp). These designs are compared with D-optimal designs for a given dose response model. Extensions to robust designs accounting for model uncertainty are also discussed. A case study is used to motivate and illustrate the methods from this paper.
Subject Headings: Dose finding
Dose response
Minimum effective dose
Model uncertainty
Robust designs
Sample size
Target dose estimation
URI: http://hdl.handle.net/2003/25988
http://dx.doi.org/10.17877/DE290R-1955
Issue Date: 2009-01-13T07:59:29Z
Appears in Collections:Sonderforschungsbereich (SFB) 475

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