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Design early phase drug combination trials: methods
Published on May 29, 2017 29 min
Other Talks in the Series: Adaptive Clinical Trial Design
Phase II clinical trials - Bayesian methods
- Prof. Fei Ye
- Vanderbilt University Medical Center, USA
Hello. My name is Ying Yuan. I'm a professor in Biostatistics at MD Anderson Cancer Center. Today I'm going to talk about how to design early phase drug combination trial.
So here is outline of the talk. First, I will talk about the challenges for designing drug combination trials then I will talk about some specific designs for drug combination trial, specifically, I will talk about how to design a trial to find a single MTD, and how to design a trial to find its MTD contour. Then I will introduce some software to implement those designs, and I will finish the talk with a summary statement.
As we know, the primary objective of phase I trial is to find its maximum tolerated dose, which is defined as a dose with a specific targeted toxicity rate like 30%. So for single-agent trials, the standard assumption is that toxicity monotonically increases with the dose. So in this case, we only find a dose with a specific target toxicity rate.
And in this monotonic assumption means, for the single-agent trial the toxicity order is known. And this greatly simplifies the dose escalation and de-escalation. For example, if we know the current dose is below the MTD, we only need to escalate the dose. If we know the current dose is above the MTD, we only needed to de-escalate the dose.
In recent years, there is a lot of interest in drug combination trial. So if you look at the medical journal, most of the published phase I trial are drug combination trials. And why people are interested in drug combination trials is it because they are looking for synergistic treatment effect.