Supporting Pharmacovigilance Signal Validation and Prioritization with Analyses of Routinely Collected Health Data: Lessons Learned from an EHDEN Network Study

Introduction Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals i...

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Published in:	Drug safety Vol. 46; no. 12; pp. 1335 - 1352
Main Authors:	Gauffin, Oskar, Brand, Judith S., Vidlin, Sara Hedfors, Sartori, Daniele, Asikainen, Suvi, Català, Martí, Chalabi, Etir, Dedman, Daniel, Danilovic, Ana, Duarte-Salles, Talita, García Morales, Maria Teresa, Hiltunen, Saara, Jödicke, Annika M., Lazarevic, Milan, Mayer, Miguel A., Miladinovic, Jelena, Mitchell, Joseph, Pistillo, Andrea, Ramírez-Anguita, Juan Manuel, Reyes, Carlen, Rudolph, Annette, Sandberg, Lovisa, Savage, Ruth, Schuemie, Martijn, Spasic, Dimitrije, Trinh, Nhung T. H., Veljkovic, Nevena, Vujovic, Ankica, de Wilde, Marcel, Zekarias, Alem, Rijnbeek, Peter, Ryan, Patrick, Prieto-Alhambra, Daniel, Norén, G. Niklas
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-12-2023 Springer Nature B.V
Subjects:	Adverse events Case reports Computer networks Consortia Cost benefit analysis Data analysis Decision analysis Decision making Drug delivery Drug Safety and Pharmacovigilance Feasibility studies Medicine Medicine & Public Health Original Original Research Article Pharmacology/Toxicology Pharmacovigilance Phenotypes Primary care Public health Signal detection Standardization Statistical methods Statistics User requirements Vaccines
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Summary:	Introduction Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. Objective The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. Methods Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. Results Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15–60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. Conclusions Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost–benefit of integrating these analyses at this stage of signal management requires further research.
Bibliography:	EC/HEU/806968
ISSN:	0114-5916 1179-1942
DOI:	10.1007/s40264-023-01353-w