Introduction There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. Methods The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). Conclusions Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.
ObjectivesTo combine spontaneously reported data from multiple countries to estimate reporting rate, and better understand risk factors for myocarditis and pericarditis following COVID-19 messenger RNA (mRNA) vaccines.DesignSystematic review of spontaneously reported data from UK, USA and European Union/European Economic Area (EU/EEA) and of the scientific literature.Data sourcesUK Yellow Card scheme, Vaccine Adverse Event Reporting System (VAERS), EudraVigilance were searched from date of vaccine launch to 14 March 2022–16 March 2022. PubMed/MEDLINE and Embase were searched to 15 March 2022.Eligibility criteriaWe included publicly available spontaneous reporting data for ‘Myocarditis’ and ‘Pericarditis’ from UK, USA and EU/EEA following COVID-19 mRNA vaccines. Pharmacoepidemiological observational studies investigating myocarditis/pericarditis following mRNA COVID-19 vaccines were included (no restrictions on language or date). Critical Appraisal Skills Programme tools assessed study quality.Data extraction and synthesisTwo researchers extracted data. Events of myocarditis and pericarditis were presented for each data source, stratified by vaccine, age, sex and dose (where available). Reporting rates were calculated for myocarditis and pericarditis for each population. For published pharmacoepidemiological studies, design, participant characteristics, and study results were tabulated.ResultsOverall, 18 204 myocarditis and pericarditis events were submitted to the UK, USA and EU/EEA regulators during the study period. Males represented 62.24% (n=11 331) of myocarditis and pericarditis reports. In the UK and USA, most reports concerned vaccinees aged <40 years (59.7% and 47.3% of reported events, respectively); trends in age were less clear for EU/EEA. Reports were more frequent following a second dose (47.1% of reports, where data available). Reporting rates were consistent between the data sources. Thirty-two pharmacoepidemiological studies were included; results were consistent with our spontaneous report analyses.ConclusionsYounger vaccinees more frequently report myocarditis and pericarditis following mRNA COVID-19 vaccines than older vaccinees. Results from published literature supported the results of our analyses.
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