Background. Globally, pharmacovigilance activities were affected by COVID-19. Therefore, several competent health authorities around the world, including several countries in the Middle East, have issued guidelines and practices to ensure that pharmacovigilance activities are maintained and continued during the pandemic. Objective. The aim of this study was to assess the impact of COVID-19, preparedness and performance of national pharmacovigilance systems in participating countries during COVID-19 pandemic. Methods. This was a cross- sectional study that was conducted between July and October 2020. National pharmacovigilance centres in 18 Arab countries in the Middle East were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. Results. Responses were obtained from 14 (77.8%) Arab countries. Ten of participating countries (71.4%) have either specific national PV guidelines or local PV practices during the COVID-19 pandemic. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centres vary considerably among participating countries during the pandemic. Conclusion. The findings highlight the differences in preparedness and performance of different national PV centres in participating Middle Eastern countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.

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. 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. 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. 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 healthdata. 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. 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.

In pharmacovigilance, signal assessment of a medicinal product and adverse event can involve reviewing prohibitively large numbers of case reports. A prototype of a decision support tool guided by a needs assessment was developed to help manual review of many reports. In a preliminary qualitative evaluation, users said the tool was easy to use, improved efficiency and provided new insights.

BackgroundStillbirth has been associated with low plasma vitamin D. Both Sweden and Finland have a high proportion of low plasma vitamin D levels (< 50 nmol/L). We aimed to assess the odds of stillbirth in relation to changes in national vitamin D fortification.MethodsWe surveyed all pregnancies in Finland between 1994 and 2021 (n = 1,569,739) and Sweden (n = 2,800,730) with live or stillbirth registered in the Medical Birth Registries. The mean incidences before and after changes in the vitamin D food fortification programs in Finland (2003 and 2009) and Sweden (2018) were compared with cross-tabulation with 95% confidence intervals (CI).ResultsIn Finland, the stillbirth rate declined from ~ 4.1/1000 prior to 2003, to 3.4/1000 between 2004 and 2009 (odds ratio [OR] 0.87, 95% CI 0.81–0.93), and to 2.8/1000 after 2010 (OR 0.84, 95% CI 0.78–0.91). In Sweden, the stillbirth rate decreased from 3.9/1000 between 2008 and 2017 to 3.2/1000 after 2018 (OR 0.83, 95% CI 0.78–0.89). When the level of the dose-dependent difference in Finland in a large sample with correct temporal associations decreased, it remained steady in Sweden, and vice versa, indicating that the effect may be due to vitamin D. These are observational findings that may not be causal.ConclusionEach increment of vitamin D fortification was associated with a 15% drop in stillbirths on a national level. If true, and if fortification reaches the entire population, it may represent a milestone in preventing stillbirths and reducing health inequalities.

Signals of adverse drug reactions (ADRs) can be supported by reports of ADRs and by interventional and non-interventional studies. The evidence base and features of ADR reports that are used to support signals remain to be comprehensively described. To this end, we have undertaken a scoping review. We searched the following databases: PubMed, EMBASE, PsycINFO, Web of Science, and Google Scholar, without language or time restrictions. We also hand searched the bibliographies of relevant studies. We included studies of any design if the results were described as signals. We assessed the levels of evidence using the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria and coded features of reports of ADRs using the Bradford Hill guidelines. Overall, 1974 publications reported 2421 studies of signals; 1683/2421 were clinical assessments of anecdotal reports of ADRs, but only 225 (13%) of these included explicit judgments on which features of the ADR reports were supportive of a signal. These 225 studies yielded 228 signals; these were supported by features, which were: 'experimental evidence' (i.e., positive dechallenge or rechallenge, 154 instances [68%]), 'temporality' (i.e., time to onset, 130 [57%]), 'exclusion of competing causes' (49 [21%]), and others (40 [17%]). Positive dechallenge/rechallenge often co-occurred with temporality (77/228). OCEBM 4 (i.e., case series and case-control studies) was the most frequent level of evidence (2078 studies). Between 2013 and 2019, there was a three-fold increase in clinical assessments of reports of ADRs compared with a less than two-fold increase in studies supported by higher levels of evidence (i.e., OCEBM 1-3). We identified an increased rate between 2013 and 2019 in disproportionality analyses (about 15 studies per year), mostly from academia. Most signals were supported by temporality and dechallenge/rechallenge, but clear reporting of judgments on causality remains infrequent. The number of studies supported only by anecdotal reports of ADRs increased from year to year. The impact of a growing number of signals of disproportionate reporting communicated without an accompanying clinical assessment should be evaluated.

ABSTRACT Background Pharmacovigilance (PV) activities were affected by COVID-19. Therefore, several health authorities around the world have issued guidelines and practices to ensure that PV activities are maintained and continued during the pandemic. This study aimed to assess the impact of COVID-19 on the preparedness and performance of national PV systems in 14 Arab countries. Research design and methods This was a cross-sectional study that was conducted between July and October 2020. National PV centers in 18 Arab countries were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. Results Responses were obtained from 14 (77.8%) countries. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centers vary considerably among participating countries during the pandemic. Conclusion The findings highlight the differences in preparedness and performance of different national PV centers in participating Arab countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.