Purpose: Data mining in spontaneous reporting databases generates large numbers of signals of disproportionate reporting (SDRs) that need to be prioritised for assessment. The pharmacological relevance of drug-event associations is not considered in SDR prioritisation algorithms. This aimed to propose and test a pharmacological score for SDR prioritisation. Methods: The Pharmacological Score for SDRs Prioritisation (PS-SP) was developed using a Delphi approach. An expert group agreed that PS-SP should include general criteria concerning SDRs and criteria concerning pharmacological relevance, and that criteria should be weighted for their risk representation. Once defined, the PS-SP was tested for prioritisation of SDRs for extrapyramidal syndrome in the French Pharmacovigilance database; the SDR classification was compared to that obtained using a traditional disproportionality approach. Results: For a given drug, the general criteria retained were the reporting rate of the adverse drug reaction (ADR) and value of the 95% confidence interval (CI) lower boundary of the Reporting Odds Ratio (ROR). Pharmacological criteria consisted of the ADR reporting rate without concomitant at-risk drugs or those indicated for ADR treatment, and the value of the ROR 95% CI lower boundary as estimated in the subset of reports concerning drugs from the same therapeutic and then pharmacological class. Compared with traditional disproportionality, PS-SP prioritised specific drugs within congeners: metoclopramide, indoramin, and trimetazidine appeared as outliers within their classes; conventional antipsychotics had higher prioritisation than atypical antipsychotics. Conclusion: The pilot evaluation of PS-SP performed in extrapyramidal syndrome advocates for the use of pharmacological criteria in SDR prioritisation algorithms.

Disproportionality, Signal detection, Signal prioritisation, Spontaneous reporting
dx.doi.org/10.1007/s00228-014-1657-2, hdl.handle.net/1765/62125
European Journal of Clinical Pharmacology
Department of Medical Informatics

Salvo, F, Raschi, E, Moretti, U, Chiarolanza, A, Fourrier-Reglat, A, Moore, N, … Pariente, A. (2014). Pharmacological prioritisation of signals of disproportionate reporting: Proposal of an algorithm and pilot evaluation. European Journal of Clinical Pharmacology, 70(5), 617–625. doi:10.1007/s00228-014-1657-2