Conditional Modeling-Based Approach for Two Dimensional Dose Finding in Phase I Trials : An Alternative Approach of Thall et al.’s Method
Date Issued
2006
Date
2006
Author(s)
Ho, Li-Ting
DOI
zh-TW
Abstract
第一期臨床試驗的主要目的在於尋找藥物安全的劑量，以備後續二、三期試驗參考。單劑量的安全劑量尋找，於統計上可看成劑量－毒性的二維反應曲線建構，當劑量推展到二劑量時，統計問題成為雙劑量－毒性之三維曲面建構，較建構二維曲面問題複雜許多，統計難度包括在雙劑量的交互作用描述及整體模式的參數估計。本研究目的在以雙劑量－毒性反應模式為基礎下，以條件模式方法將雙劑量－毒性反應轉化為二個條件單劑量－毒性反應模式，這種作法的好處在於條件模式仍可反映雙劑量之交互作用，且可以避免直接處理雙劑量模式的複雜性。
The primary purpose of a phase I clinical trial is to determine the safety dose of a new drug for later trials use. Many statistical methods have been proposed for the determination of dose for a single drug. In statistical sense it can be regarded as a two-dimensional dose-toxicity curve fitting problem. In many trials, however, investigators are more interested in finding the doses for multiple agents. When there are multiple agents, statistical problem becomes more complicated due to the interaction among agents, and the monotonicity between toxicity and dose can no longer be assumed as that in the case of a single agent. For a two-agent trial, we have to deal with the three-dimensional curve fitting problem. A previous method used a joint-probability regression model to undergo the model-setting for toxicity response curve with two agents. Hence, we modify this method by dividing the model into two conditional models. Each conditional model describes the toxicity reaction of an agent conditional on the other agent. The advantage of our method is to avoid complexity in estimation but still retain the capability of the original method in coping with interaction between two agents.
Subjects
曲面尋找
劑量反應
curve finding
dose response
Type
thesis