(W) Benefit Risk Contextualisation of COVID-19 Vaccines in the EU

Publication Number: 313

Background: The main public health priority during the pandemic is maintaining mortality as low as possible and minimising pandemic induced health and economic distress. To achieve this goal, several vaccines against SARS-CoV-2 induced COVID-19 disease were developed rapidly, all while adhering to stringent quality standards. COVID-19 vaccines are highly effective in lowering the risk of contracting and spreading the virus, as well as lowering the severity of symptoms, thereby decreasing the overall COVID-19 disease burden.

Objectives: To propose a method to quantify the benefits and risks of COVID-19 vaccines and to develop a user tool for assessing this benefit-risk, using myocarditis, pericarditis and thrombosis with thrombocytopenia (TTS) as adverse events of interest.

Methods: Using a probabilistic model to account for differential vaccine effectiveness and temporal differences in disease dynamics, the benefit of different vaccines in the European Economic Area (EEA) were calculated by comparing the observed number of confirmed cases, hospitalisations, ICU admissions and deaths (source ECDC) with the expected number of these events, had no COVID-19 vaccines been available. Risks of myocarditis, pericarditis and TTS associated with the vaccines was evaluated by comparing the observed risk events (source EudraVigilance) to the expected events based on background incidence rates (source EMA).

Results: The vaccines under study had comparable benefits, but magnitude differed by age group, gender and vaccine product. When relying on published vaccine effectiveness estimates, the benefit of vaccination was estimated by the prevention of 13,322,567 confirmed COVID-19 infections, 933,230 COVID-19 hospitalisations, 150,106 ICU admissions and 220,880 COVID-19 related deaths in the EEA, since the start of vaccination. While there was an increased risk of myocarditis in the male population < 40 years of age after Spikevax vaccination, the vaccine prevented substantial COVID-19 hospitalisations in this population. Both the number of clinical benefits, as well as the risk of TTS after Vaxzevria vaccination were the highest in the 60 to 69 years of age category, with benefits outweighing the risk.

Conclusions: This analysis demonstrates that the benefits of COVID-19 vaccination far outweigh the myocarditis, pericarditis and TTS risks. Rare, life-threatening side effects associated with vaccination might not be observed in a clinical trial and should be investigated as soon as possible after introduction of vaccines into large populations. The proposed methodology can be applied to any serious adverse event that may occur in the future or other vaccines.