RESUMO
Background: The real-world safety profile of COVID-19 mRNA vaccines remains incompletely elucidated. Methods: We performed a nationwide post-market safety surveillance analysis in Singapore, on vacinees aged 5 years and older, through mid-September 2022. Observed-over-expected (O/E) analyses were performed to identify potential safety signals among eight shortlisted adverse events of special interest (AESIs): strokes, cerebral venous thrombosis (CVT), acute myocardial infarction, myocarditis/pericarditis, pulmonary embolism, immune thrombocytopenia, convulsions and appendicitis. Self-controlled case series analyses (SCCS) were performed to validate signals of concern, occurring within 42 days of vaccination. Findings: Elevated risks were observed on O/E analyses for the following AESIs: myocarditis/pericarditis, [rate ratio (RR): 3.66, 95 % confidence interval (95 % CI): 2.71 to 4.94], appendicitis [RR: 1.14 (1.02 to 1.27)] and CVT [RR: 2.11 (1.18 to 3.77)]. SCCS analyses generated corroborative findings: myocarditis/pericarditis, [relative incidence (RI): 6.96 (3.95 to 12.27) at 1 to 7 days post-dose 2], CVT [RI: 4.30 (1.30 to 14.20) at 22 to 42 days post-dose 1] and appendicitis [RI: 1.31 (1.03 to 1.67) at 1 to 7 days post-dose 1]. Booster dose 1 continued to be associated with higher rates of myocarditis/pericarditis on O/E analysis [RR: 2.30, (1.39 to 3.80) and 1.69, (1.11 to 2.59)] at 21- and 42-days post-booster dose 1, respectively. Males aged 12 to 17 exhibited highest risks of both myocarditis/pericarditis [RI: 6.31 (1.36 to 29.3)] and appendicitis [RI: 2.01 (1.12 to 3.64)] after primary vaccination. Similarly, CVT was also predominantly observed in males aged above 50 (11 out of 16 cases), within 42-days of vaccination. Interpretation: Our data suggest that myocarditis/pericarditis, appendicitis and CVT are associated with primary vaccination using COVID-19 mRNA vaccines. Males at specific ages exhibit higher risks for all three AEs identified. The risk of myocarditis/pericarditis continues to be elevated after booster dose 1.
RESUMO
OBJECTIVES: The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to a common data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefit-risk assessments in post-market regulatory evaluation and decisions. METHODS: EMRs from January 2013 to December 2016 were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappings were applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a prior OMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrial fibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed to represent the comparative effectiveness, safety and utilization of the drugs. RESULTS: Over 90% of records were mapped onto the OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. In total, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable via the proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfully inform regulatory decision-making. CONCLUSIONS: While the structure of the OMOP-CDM and its accessory tools facilitate real-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-risk assessments, may require layering on additional analytic tools and visualization techniques.
