A practical design for a dual-agent dose-escalation trial that incorporates pharmacokinetic data

Cotterill, Amy and Lorand, D. and Wang, J. and Jaki, Thomas (2015) A practical design for a dual-agent dose-escalation trial that incorporates pharmacokinetic data. Statistics in Medicine, 34 (13). pp. 2138-2164. ISSN 0277-6715

Full text not available from this repository.

Abstract

Traditionally, model-based dose-escalation trial designs recommend a dose for escalation based on an assumed dose-toxicity relationship. Pharmacokinetic data are often available but are currently only utilised by clinical teams in a subjective manner to aid decision making if the dose-toxicity model recommendation is felt to be too high. Formal incorporation of pharmacokinetic data in dose-escalation could therefore make the decision process more efficient and lead to an increase in the precision of the resulting recommended dose, as well as decreasing the subjectivity of its use. Such an approach is investigated in the dual-agent setting using a Bayesian design, where historical single-agent data are available to advise the use of pharmacokinetic data in the dual-agent setting. The dose-toxicity and dose-exposure relationships are modelled independently and the outputs combined in the escalation rules. Implementation of stopping rules highlight the practicality of the design. This is demonstrated through an example which is evaluated using simulation.

Item Type:
Journal Article
Journal or Publication Title:
Statistics in Medicine
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2600/2613
Subjects:
ID Code:
73143
Deposited By:
Deposited On:
04 Mar 2015 17:02
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Jan 2020 09:09