Bridging solutions in dose-finding problems Journal Article


Authors: O'Quigley, J.; Iasonos, A.
Article Title: Bridging solutions in dose-finding problems
Abstract: The idea of bridging in dose-finding studies is closely linked to the problem of group heterogeneity. There are some distinctive features in the case of bridging which need to be considered if efficient estimation of the maximum tolerated dose (MTD) is to be accomplished. Here, we consider the case of two distinct populations. In the bridging setting we usually have in mind two studies, corresponding to the two populations. In some cases, the first of these studies may have been completed while the second has yet to be initiated. In other cases, the studies take place simultaneously and information can then be shared among the two groups. The methodological problem is how to make most use of the information gained in the first study to help improve efficiency in the second. We describe the models that we can use for the purpose of bridging and study situations in which their use leads to overall improvements in performance as well as cases where there is no gain when compared to carrying out parallel studies. Simulations and an example in pediatric oncology help to provide further insight. © 2014 © American Statistical Association.
Keywords: cisplatin; temozolomide; calibration; childhood cancer; drug dose escalation; confidence interval; simulation; probability; population; maximum tolerated dose; toxicity; clinical trials; pharmacokinetics; phase 1 trials; sample size; clinical trial (topic); statistical distribution; continual reassessment method; maximum likelihood method; dose escalation; human; article; pediatric trials
Journal Title: Statistics in Biopharmaceutical Research
Volume: 6
Issue: 2
ISSN: 1946-6315
Publisher: American Statistical Association  
Date Published: 2014-05-01
Start Page: 185
End Page: 197
Language: English
DOI: 10.1080/19466315.2014.906365
PROVIDER: scopus
PMCID: PMC4111208
PUBMED: 25071878
DOI/URL:
Notes: Stat. Biopharm. Res. -- Export Date: 8 July 2014 -- Source: Scopus
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  1. Alexia Elia Iasonos
    362 Iasonos