Impact of methodological choices on findings from pharmacoepidemiological studies: Final results of the IMI-protect (pharmacoepidemiological research on outcomes of therapeutics by a European consortium) project

Abstract

Background: Pharmacoepidemiological (PE) research should provide consistent, reliable and reproducible results to contribute to the benefit-risk assessment of medicines. IMI-PROTECT aims to identify sources of methodological variations in PE studies using a common protocol and analysis plan across databases (including independent replication studies). In addition, differences by design, applied to a same drug-adverse event (AE) pair in different databases are examined. Results from PE studies will be evaluated on 7 drug-AE pairs (i.e. 1. antibiotics and acute liver injury; 2. antidepressants and hip fracture; 3. benzodiazepines and hip fracture; 4. anticonvulsants and suicide/suicide attempts; 5. calcium channel blockers and malignancies; 6. inhaled longacting β2 agonists and acute myocardial infarction; 7. a negative control study: antibiotics and acute myocardial infarction) conducted in 7 European and 1 US electronic databases. These are: the CPRD and THIN from the UK, the Danish national registries, the Dutch Mondriaan project (NPCRD, AHC), the Spanish BIFAP, the French PGRx and the US InVision Datamart. Objectives: To review and understand the methodological issues encountered in these studies and to draw conclusions about their relevance for future PE research.