Print page Resize text Change font-size Change font-size Change font-size High contrast

Home > Standards & Guidances > Methodological Guide

ENCePP Guide on Methodological Standards in Pharmacoepidemiology


5.4. Triangulation


Triangulation is not a separate methodological approach, but rather a research paradigm of approaching causality, as formally described in Triangulation in aetiological epidemiology (Int J Epidemiol. 2016;45(6):1866-86) and defined as “the practice of obtaining more reliable answers to research questions through integrating results from several different approaches, where each approach has different key sources of potential bias that are unrelated to each other.” This publication proposes a minimum set of practical criteria for a valid triangulation. It explains that approaches used in many non-randomised pharmacoepidemiological studies, such as control exposures and outcomes, sensitivity analyses, comparing results from different populations and study designs, can consider biases in opposite directions all within the same study, explicitly specifying the direction of the respective biases.


Triangulation was used (without using the explicit term) in Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring (JAMA. 2017;317(15):1553-62), whereby, within the same study and using the same data, the authors used negative controls (paternal exposure to antidepressants) and assessed the association using different study designs, including  a sibling design.


In Triangulation of pharmacoepidemiology and laboratory science to tackle otic quinolone safety (Basic Clin Pharmacol Toxicol. 2022;Suppl 1:75-80) laboratory studies using cell culture and rodent models were complemented with real-world data from pharmacoepidemiological studies to translate mechanistic findings and corroborate real-world evidence. In Identifying Antidepressants Less Likely to Cause Hyponatremia: Triangulation of Retrospective Cohort, Disproportionality, and Pharmacodynamic Studies (Clin Pharmacol Ther. 2022; 111(6):1258-67) analyses of three different types of data with their respective analyses are presented: a retrospective cohort study, a disproportionality analysis of patients in the Japanese Adverse Drug Event Report database, and a pharmacodynamic study examining the binding affinity for serotonin transporter.



« Back