• J Biopharm Stat · Jan 2007

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

    • Frank Miller, Olivier Guilbaud, and Holger Dette.
    • Clinical Information Science, AstraZeneca, Södertälje, Sweden. frank.miller@astrazeneca.com
    • J Biopharm Stat. 2007 Jan 1; 17 (6): 1097-115.

    AbstractWe 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 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 key parts 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 nonadaptive 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 a gain in information, or essential savings in sample size. Further, we investigate an adaptive Bayesian optimal design that uses different optimal designs before and after an interim analysis, and we compare the adaptive with the nonadaptive Bayesian optimal design. The basic concept is illustrated using a modification of a recent AstraZeneca trial.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…