ABSTRACT

Much of historical drug development has been based on a one-size-ˆtsall paradigm. However, as the slowdown in the number of the new drug approvals demonstrates, this strategy is becoming less viable [1]. The FDA Critical Path Initiative [2] calls for a focus on personalized medicine

CONTENTS

2.1 Introduction .................................................................................................. 11 2.1.1 Introductory Concepts and Philosophy ....................................... 13 2.1.2 Basics of Drug/Diagnostics Codevelopment ............................... 13

2.1.2.1 PHC Assessment versus Development Strategy .......... 14 2.2 POC Designs ................................................................................................. 16

2.2.1 Overall Considerations ................................................................... 17 2.2.2 Operational Considerations ........................................................... 17 2.2.3 Statistical Considerations................................................................ 18

2.2.3.1 Deˆning Decision Rules ................................................... 19 2.2.3.2 Sample Size Considerations ............................................. 19

2.3 Brief Phase III Considerations .................................................................... 24 2.4 Performing Exploratory Analyses ............................................................. 24

2.4.1 Planning, Documentation, and Communications ...................... 26 2.4.2 Data Generation ............................................................................... 26 2.4.3 Fit-for-Purpose Statistical Analysis and Criteria ........................ 26 2.4.4 Assessing and Interpreting Statistical Evidence ......................... 27 2.4.5 Cutoff Selection for Continuous Biomarkers ............................... 27 2.4.6 Developing a Complex Predictor ...................................................28 2.4.7 Validation Strategy ..........................................................................28