Adaptive designs for phase I trials 1

Published on September 29, 2016   31 min

Other Talks in the Series: Adaptive Clinical Trial Design

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Hi, my name is Anastasia Ivanova from the Department of Biostatistics, University of North Carolina at Chapel Hill. And today, we're gonna talk about Adaptive Designs for Phase I Trials. These designs were developed and are used in Phase I trials in oncology. Some of these designs can be used in Phase I and mostly Phase II trials in areas other than oncology. Since these designs are mostly used in oncology, I will focus on oncology applications throughout this lecture.
In oncology, we usually consider several fixed doses from three to eight. And we assume that the probability of toxicity is non-decreasing with the dose. Here, on this plot, I have a curve showing the probability of toxicity as a function of dose. The goal of a Phase I trial in oncology is usually to find the Maximum Tolerated Dose or MTD. The MTD is defined as a dose with a certain probability of toxicity, usually 20%. In oncology, the primary outcome in dose-finding studies is actually the Dose Limiting Toxicity, but I will use these two terms interchangeably DLT or toxicity.
So as I said, the Maximum Tolerated Dose is defined as the dose where the probability of toxicity is equal to a certain number but you know this number as Γ. And Γ is usually 20% in Phase I trials in oncology.
Why do we need to find the MTD in oncology trials? Usually, we assume the therapeutic effect of a drug is increasing with the dose. Therefore, lower doses are usually not efficacious. Due to toxicity, we cannot administer higher doses to most of the subjects. Therefore, the goal is to find the dose with a tolerable toxicity rate. This dose then is investigated in a subsequent Phase II trial. In non life-threatening diseases, the MTD is the highest dose in the range of doses that are further investigated in the Phase II trial.

Adaptive designs for phase I trials 1

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