Pharmacological prioritisation of signals of disproportionate reporting: proposal of an algorithm and pilot evaluation

• Published in: European journal of clinical pharmacology Vol. 70; no. 5; pp. 617 - 625
• Main Authors: Salvo, Francesco, Raschi, Emanuel, Moretti, Ugo, Chiarolanza, Anita, Fourrier-Réglat, Annie, Moore, Nicholas, Sturkemboom, Miriam, De Ponti, Fabrizio, Poluzzi, Elisabetta, Pariente, Antoine
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2014; Springer; Springer Nature B.V
• Subjects: Adverse Drug Reaction Reporting Systems - organization & administration; Adverse Drug Reaction Reporting Systems - statistics & numerical data; Algorithms; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Clinical trial. Drug monitoring; Data mining; Data Mining - methods; Data Mining - statistics & numerical data; Databases, Factual; Drug-Related Side Effects and Adverse Reactions - epidemiology; General pharmacology; Humans; Medical Informatics Computing; Medical sciences; Odds Ratio; Online data bases; Pharmacoepidemiology and Prescription; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pilot Projects; Disproportionality; Signal prioritisation; Spontaneous reporting; Signal detection; Human; Drug; Evaluation; Toxicity; Safety signal; Spontaneous notification; Algorithm
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-014-1657-2

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.