Abstract:
:Most phase I dose-finding methods in oncology aim to find the maximum-tolerated dose from a set of prespecified doses. However, in practice, because of a lack of understanding of the true dose-toxicity relationship, it is likely that none of these prespecified doses are equal or reasonably close to the true maximum-tolerated dose. To handle this issue, we propose an adaptive dose modification (ADM) method that can be coupled with any existing dose-finding method to adaptively modify the dose, when it is needed, during the course of dose finding. To reflect clinical practice, we divide the toxicity probability into three regions: underdosing, acceptable, and overdosing regions. We adaptively add a new dose whenever the observed data suggest that none of the investigational doses are likely to be located in the acceptable region. The new dose is estimated via a nonparametric dose-toxicity model based on local polynomial regression. The simulation study shows that ADM substantially outperforms the similar existing method. We applied ADM to a phase I cancer trial. Copyright © 2016 John Wiley & Sons, Ltd.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Chu Y,Pan H,Yuan Ydoi
10.1002/sim.6933subject
Has Abstractpub_date
2016-09-10 00:00:00pages
3497-508issue
20eissn
0277-6715issn
1097-0258journal_volume
35pub_type
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