Flexible seamless designs for clinical trials in the development of targeted treatments

• Applicant: Professorin Dr. Nina Timmesfeld, since 7/2013
• Subject Area: Epidemiology and Medical Biometry/Statistics
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 228173686

Molecular and genetic biomarkers offer the potential to identify highly treatment responsive subsets of patients with diseases which appear phenotypically homogenous. In this project, flexible design methods are developed for the interim selection of sub-populations in randomized clinical trials based on interim results. A typical illustrative application of such designs is a cancer trial in which response to the experimental treatment is expected to depend on molecular markers of the tumour. Initially, patients with all molecular types of the tumour are randomized. After an interim inspection of the data, the researcher may decide to restrict further randomization on selected molecular subtypes for which the experimental treatment appears most promising, according to interim data such as response rates and/or partial survival information. Neither the formal selection rule nor the time point of the interim look has to be pre-specified. Data inspections can be made repeatedly during the course of a trial. We will use a combination of the CRP principle in its recent extensions for survival studies (Irle and Schäfer, JASA 2012) and the closed testing principle to provide full control of the family type I error risk.

• DFG Programme: Research Grants
• International Connection: USA
• Participating Persons: Professor Dr. Hajo Holzmann; Professor Dr. Cyrus Mehta; Professor Dr. Helmut Schäfer
• Ehemaliger Antragsteller: Dr. Sebastian Irle, until 6/2013