The European Drug-Drug Interaction (EuroDDI) Study Protocol: A Cross-Country Comparison of Drug-Drug Interaction Prevalence in the Older Community-Dwelling Population

Background: Drug-drug interactions (DDIs), highly prevalent amongst the elderly, can lead to avoidable medication-related harm. Cardiovascular and central nervous system (CNS) drugs are commonly implicated. To date, there is no consensus on how to measure DDIs, making comparisons across countries challenging.

Objective: To (i) establish a common data model (CDM) to measure DDI prevalence in the older (aged ≥ 70 years) community-dwelling population of three European countries and (ii) compare and describe cardiovascular and CNS DDI prevalence rates across these countries.

Methods: This cross-country study will apply a harmonised method of DDI identification and analysis using the WHO ATC classification system and national pharmacy claims data from three European countries (Ireland, Italy, Spain). Patients aged ≥ 70 years dispensed ≥ 2 medications during 2016 will be identified from each country's national database. 'Severe' cardiovascular and CNS DDIs (i.e., may result in a life-threatening event/permanent detrimental effect) will be identified using the British National Formulary and Stockley's Drug Interactions. Two separate lists of 'severe' DDIs, per medications reimbursed, will be applied to each database: (i) DDIs relevant to each individual country and (ii) DDIs relevant to all three countries. DDIs will be defined as co-dispensed (same day) and concomitantly (±7 days) dispensed.

Results: Descriptive statistics, including DDI prevalence and 95% confidence intervals, will be reported for each country. Prevalence will be pooled and compared across countries using random effects models and meta-regression, where feasible.

Conclusion: The EuroDDI study will develop a harmonised method to measure and compare DDI prevalence across health-related databases in Europe.