English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Phase I dose-escalation trials constitute the first step in investigating thesafety of potentially promising drugs in humans. Conventional methods for phaseI dose-escalation trials are based on a single treatment schedule only. Morerecently, however, multiple schedules are more frequently investigated in thesame trial. Here, we consider sequential phase I trials, where the trialproceeds with a new schedule (e.g. daily or weekly dosing) once the doseescalation with another schedule has been completed. The aim is to utilize theinformation from both the completed and the ongoing dose-escalation trial toinform decisions on the dose level for the next dose cohort. For this purpose,we adapted the time-to-event pharmacokinetics (TITE-PK) model, which wereoriginally developed for simultaneous investigation of multiple schedules.TITE-PK integrates information from multiple schedules using a pharmacokinetics(PK) model. In a simulation study, the developed appraoch is compared to thebridging continual reassessment method and the Bayesian logistic regressionmodel using a meta-analytic-prior. TITE-PK results in better performance thancomparators in terms of recommending acceptable dose and avoiding overly toxicdoses for sequential phase I trials in most of the scenarios considered.Furthermore, better performance of TITE-PK is achieved while requiring similarnumber of patients in the simulated trials. For the scenarios involving oneschedule, TITE-PK displays similar performance with alternatives in terms ofacceptable dose recommendations. The \texttt{R} and \texttt{Stan} code for theimplementation of an illustrative sequential phase I trial example is publiclyavailable at https://github.com/gunhanb/TITEPK_sequential.

A Bayesian time-to-event pharmacokinetic model for sequential phase I dose-escalation trials with multiple schedules