| Abstract: |
A drug-drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics and/or pharmacodynamics of one or more other drugs. Pharmacoepidemiology studies are the principal way of studying the health effects of potential DDIs. A number of methodologic problems are more prominent in pharmacoepidemiologic studies of DDIs than in those examining the effects of individual drugs. These include confounding by indication, the inability of healthcare data to validly identify all study outcomes of potential interest, and the need to optimize pharmacoepidemiologic methods to perform well in screening for previously unanticipated associations. Available research designs for studying the health effects of potential drug-drug interactions include the cohort, nested case-control, self-controlled case series, and case-crossover designs, sometimes employing positive and/or negative control object drugs and/or precipitant drugs. Additional considerations include the order of concomitancy of the object and precipitant, and the need to study the time course of the DDI. Given the continued development of new drugs, repurposing of old drugs, the rising frequency of polypharmacy, and the aging of the population, the clinical and public health importance of DDIs will continue to grow. Numerous developments are foreseeable, including use of larger population databases and expanding the scope of studies to hospitalized patients and other populations. Finally, there is an urgent need to develop and test approaches to better incorporate the knowledge gained through studies of the health effects of DDIs into the healthcare system. © 2020 John Wiley & Sons Ltd. |
