SESSION F

TITLE: Modern Dose Finding Designs – Advances and hot topics
SPEAKER: Frank Fleischer, PhD, Boehringer-Ingelheim Pharma GmbH & Co. KG
MODERATOR: Naitee Ting

 

Abstract

Approaches to dose finding designs have improved a lot both for parallel group as well as for up-and-down designs. Multiple-comparison procedures and modelling (MCPMod,[1],[2]) and Bayesian logistic regression models (BLRM, [3],[4]) have become standard techniques in these settings leading to more efficient and precise dose  and MTD determination. This short course will start with an introduction into the elementary principles of dose finding and the two approaches. Exposure-based and other possibilities for incorporating different schedules and regimens are discussed and compared.  A fully Bayesian approach to MCPMod (BMCPMod) will be introduced that is able to combine the advantages of MCPMod with Bayesian data augmentation ([4],[5]). We will show simulation results as well as case studies in the normal and binary data setting for BMCPMod demonstrating the benefits of the approach. For the BLRM different extensions are discussed like combination models with more than two combination partners and the integration of covariates. A joint model for BLRMs will be explained ([6]) that can simultaneously cope with parallel dose escalations in different mono and combination settings. The course will conclude with some examples of applications for these techniques in clinical trials and some practical issues and experiences related to that.

Reference

Neuenschwander, B., Branson, M., Gsponer, G.. Critical aspects of the Bayesian approach to phase I cancer trials. Statistics in Medicine (2008):27,2420–39.

 

Speakers’s Bio:

Dr. Frank Fleischer, Head of Methodology Statistics, Boehringer-Ingelheim Pharma GmbH & Co. KG. Being a trained mathematician and statistician Frank has worked for more than 10 years in the pharmaceutical industry. He is heading a global team of statisticians at Boehringer Ingelheim focusing on statistical methodology and the implementation of innovative statistical designs into practice. In that role, Frank and his team are considered with methodological questions regarding adaptive designs, statistical decision making, dose finding and Bayesian borrowing designs as well as with piloting these methods in clinical trials. Through this function several projects across different therapeutic areas and phases are supported. Formerly he has been a lead project statistician for different projects in oncology, immunology and the biosimilars.

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