Clinical Studies of Drug-Drug Interactions: Design and Interpretation

The potential importance of drug-drug interaction (DDIs) is increasing as polypharmacy becomes more and more prevalent. In vitro data cannot directly predict clinical DDIs, but may provide a rationale for initiation of human studies to confirm or exclude possible interactions. Clinical DDI studies are designed to determine whether there is a real drug interaction not due to chance, how big the interaction is, and whether the DDI is of clinical importance. Statistical significance is not equivalent to clinical significance, and supplemental pharmacodynamic or clinical outcome information is needed to address the importance of a pharmacokinetic DDI.