### Adaptive designs for dose escalation studies - a simulation study

Roth, K *(Bayer Schering Pharma AG)*

Thursday 14 August 2008, 09:30-10:00

Seminar Room 1, Newton Institute

#### Abstract

Dose escalation studies are used to find the maximum tolerated dose of a new drug. They are among the first studies where the new drug is used in humans, therefore little prior knowledge about the tolerability of the drug is available. Additionally, ethical restrictions have to be considered. To account for this, adaptive approaches are adequate. Most of the current standard methods like the 3+3-design are not based on optimal design theory suggesting that there is room for improvement. In a simulation study using four different dose-response-scenarios, three adaptive approaches to find the maximum tolerated dose (MTD) are compared. The traditional 3+3-design is compared to a Bayesian approach using the software tool "Bayesian ADEPT". The third approach is a parametric modification of the 3+3-design, where the 3+3-design is conducted until enough information is gathered to construct locally optimal designs based on a logistic model. It is shown that the Bayesian approach performs best in determining the correct MTD, but at the cost of treating a lot of patients at toxic doses, which makes it less feasible for practical use. The 3+3-design is more conservative, tending to underestimate the MTD but treating only few patients at toxic doses. The parametric modification of the 3+3-design has higher chances of finding the correct dose while increasing the risk for the treated patients only very slightly, and therefore is a promising alternative to the traditional 3+3-design.

#### Presentation

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