Optimal designs for estimating the interesting part of a dose-effect curve

Frank Miller, Holger Dette and Olivier Guilbaud

No 2007,21, Technical Reports from Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen

Abstract: We consider a dose-finding trial in phase IIB of drug development. For choosing an appropriate design for this trial the specification of two points is critical: an appropriate model for describing the dose-effect relationship and the specification of the aims of the trial (objectives), which will be the focus in the present paper. For many practical situations it is essential to have a robust trial objective that has little risk of changing during the complete trial due to external information. An important and realistic objective of a dose-finding trial is to obtain precise information about the interesting part of the dose-effect curve. We reflect this goal in a statistical optimality criterion and derive efficient designs using optimal design theory. In particular we determine non-adaptive Bayesian optimal designs, i.e. designs which are not changed by information obtained from an interim analysis. Compared with a traditional balanced design for this trial it is shown that the optimal design is substantially more efficient. This implies either again in information or essential savings in sample size. Further, we investigate an adaptive Bayesian optimal design that uses two different optimal designs before and after an interim analysis, and we compare the adaptive with the non-adaptive Bayesian optimal design. The basic concept is illustrated using a modification of a recent AstraZeneca trial.

Keywords: adaptive design; Bayesian design; clinical trial; dose-finding; optimal design; interesting part of dose-e?ect curve; prior knowledge; two-stage design (search for similar items in EconPapers)
Date: 2007
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.econstor.eu/bitstream/10419/25006/1/550479864.PDF (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:zbw:sfb475:200721

Access Statistics for this paper

More papers in Technical Reports from Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen Contact information at EDIRC.
Bibliographic data for series maintained by ZBW - Leibniz Information Centre for Economics ().