A dose–schedule finding design for phase I–II clinical trials

Beibei Guo, Yisheng Li and Ying Yuan

Journal of the Royal Statistical Society Series C, 2016, vol. 65, issue 2, 259-272

Abstract: type="main" xml:id="rssc12113-abs-0001">

Dose finding methods aiming at identifying an optimal dose of a treatment with a given schedule may be at a risk of misidentifying the best treatment for patients. We propose a phase I–II clinical trial design to find the optimal dose–schedule combination. We define schedule as the method and timing of administration of a given total dose in a treatment cycle. We propose a Bayesian dynamic model for the joint effects of dose and schedule. The model proposed allows us to borrow strength across dose–schedule combinations without making overly restrictive assumptions on the ordering pattern of the schedule effects. We develop a dose–schedule finding algorithm to allocate patients sequentially to a desirable dose–schedule combination, and to select an optimal combination at the end of the trial. We apply the proposed design to a phase I–II clinical trial of a γ-secretase inhibitor in patients with refractory metastatic or locally advanced solid tumours, and we examine the operating characteristics of the design through simulations.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
http://hdl.handle.net/10.1111/rssc.2016.65.issue-2 (text/html)
Access to full text is restricted to subscribers.

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:bla:jorssc:v:65:y:2016:i:2:p:259-272

Ordering information: This journal article can be ordered from
http://ordering.onli ... 1111/(ISSN)1467-9876

Access Statistics for this article

Journal of the Royal Statistical Society Series C is currently edited by R. Chandler and P. W. F. Smith

More articles in Journal of the Royal Statistical Society Series C from Royal Statistical Society Contact information at EDIRC.
Bibliographic data for series maintained by Wiley Content Delivery ().