Evaluation of inter-rater agreement between three causality assessment methods used in pharmacovigilance

Causality assessment is the evaluation of a possibility that a particular treatment is the cause of an adverse event. It plays a key role in pharmacovigilance both toward signal generation and risk benefit evaluation. There are several methods and algorithms for causality assessment, but none is considered the gold standard and use varies from country to country. This is due to inter-individual variation in using the methods as also varying sensitivities and specificities of each method. Bayesian methods of causality have greater credence but have lower acceptance as they are rigorous to perform and involve use of complex calculations. In the absence of a universally accepted method the present study was carried out to assess the intra- and inter-rater variations among three widely used causality methods—the WHO-UMC method (recommended by the Pharmacovigilance Program of India (PvPI)), Naranjo’s algorithm (a widely quoted method in case reports in literature) and the European ABO method (used in European Union to harmonize decision making). To the best of our knowledge, a study comparing these three methods has never been carried out.