Study Design of a Drug-Drug Interaction Trial Using Group Sequential Methods

• Activity Number: 423
• Type: Contributed
• Date/Time: Tuesday, August 2, 2011 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Wei Zhang*+
• Companies: Eli Lilly and Company
• Keywords: group sequential methods ; drug-drug interaction ; sample size calculation ; interim analysis

Abstract

Drugs can interact with each other in a number of ways. The most common interaction, metabolic drug interaction, relates to how the liver metabolizes the drug substances. The substantial changes in exposure arising from metabolic drug interaction can alter the safety and efficacy profile of a drug in important ways. If sponsor wish to make a specific claim in product label that no drug-drug interaction is expected, then a confirmatory trial will need to be conducted to draw the conclusion. In general, a drug-drug interaction study requires 20-30 subjects to complete. This sample size would be a moderate number for healthy volunteers, but it usually causes considerable enrollment problem when an oncology compound is studied on cancer patients, due to the low expected enrollment rate. I propose a study design using group sequential methods to evaluate drug-drug interaction. This design allows an interim analysis that could possibly stop the study early for conclusion. Study design considerations, methods, sample size calculation, planned analyses, and computing, will be discussed.