Population-based assessments of clinical drug-drug interactions: qualitative indices or quantitative measures?

Population-based assessments of drug-drug interactions have become more common since the introduction and acceptance of the population pharmacokinetic approach. Unlike traditional methods, population-based studies provide clinically relevant results that can be applied directly to a target patient population. Furthermore, population-based studies do not demand the traditional requirements of intensive pharmacokinetic sampling, rigorous inpatient stays, or stringent assessment schedules. As such, the population-based approach can effectively be used to confirm known drug-drug interactions and further characterize anticipated interactions. A prospectively designed analysis can also reveal drug-drug interactions that might otherwise have gone undetected with traditional methods. Ultimately, these results could help to alleviate clinicians' concerns about using widely marketed drugs in combination therapies and also reduce patients' risk of experiencing unacceptable side effects. This article intends to provide a balanced overview of the population-based approach and its merits, drawbacks, and potential utility in the assessment of drug-drug interactions during clinical drug development.