Arbeitspapier
Practical considerations for optimal designs in clinical dose finding studies
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.
- Language
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Englisch
- Bibliographic citation
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Series: Technical Report ; No. 2008,22
- Subject
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dose finding
robust designs
model uncertainty
minimum effective dose
dose response
target dose estimation
sample size
- Event
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Geistige Schöpfung
- (who)
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Bretz, Frank
Dette, Holger
Pinheiro, José
- Event
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Veröffentlichung
- (who)
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Technische Universität Dortmund, Sonderforschungsbereich 475 - Komplexitätsreduktion in Multivariaten Datenstrukturen
- (where)
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Dortmund
- (when)
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2008
- Handle
- Last update
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10.03.2025, 11:44 AM CET
Data provider
ZBW - Deutsche Zentralbibliothek für Wirtschaftswissenschaften - Leibniz-Informationszentrum Wirtschaft. If you have any questions about the object, please contact the data provider.
Object type
- Arbeitspapier
Associated
- Bretz, Frank
- Dette, Holger
- Pinheiro, José
- Technische Universität Dortmund, Sonderforschungsbereich 475 - Komplexitätsreduktion in Multivariaten Datenstrukturen
Time of origin
- 2008
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Strong approximation of eigenvalues of large dimensional Wishart matrices by roots of generalized Laguerre polynomials
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Geometric construction of optimal designs for dose-responsemodels with two parameters
A practical guide for optimal designs of experiments in the Monod model
Practical considerations for optimal designs in clinical dose finding studies
A note on nonparametric estimation of the effective dose in quantal bioassay
Optimal designs for dose finding studies
Optimal designs for dose finding experiments in toxicity studies
Response-adaptive dose-finding under model uncertainty
A finite sample comparison of nonparametric estimates of the effective dose in quantal bioassay
On robust and efficient designs for risk estimation in epidemiologic studies
Canonical moments, orthogonal polynomials with application to statistics
Strong approximation of eigenvalues of large dimensional Wishart matrices by roots of generalized Laguerre polynomials
Optimal designs for dose-response models with restricted design spaces
Geometric construction of optimal designs for dose-responsemodels with two parameters
A practical guide for optimal designs of experiments in the Monod model
Practical considerations for optimal designs in clinical dose finding studies