Key result
Moderna COVID-19 vaccine linked to ~212% greater myocarditis risk in self-controlled case series.
Why the study?
The study aimed to evaluate the extent of bias from violating the core assumption of event-dependent exposures when using self-controlled designs to examine COVID-19 vaccines and myocarditis.
Do different self-controlled study designs yield comparable estimates of the risk of myocarditis following COVID-19 vaccination in adults?
Observational (n=1,757)
Yes
Do different self-controlled study designs yield comparable estimates of the risk of myocarditis following COVID-19 vaccination in adults?
Different self-controlled study designs (SCCS and SCRI) yield largely comparable results when evaluating the risk of myocarditis following COVID-19 vaccination, despite potential violations of the event-dependent exposure assumption.
Discrepant myocarditis risk estimates by design for Moderna warrant caution; leaves open standardization of self-controlled methods.
Introduction The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. Methods We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. Results We included 1,757 cases of myocarditis. In unadjusted analyses, agreement between study designs varied by vaccine brand. There was good agreement between all designs for AstraZeneca and Pfizer, but for Moderna we found harmful incidence rate ratios (IRR) using the standard and extended SCCS (standard SCCS: IRR = 3.12, 95%CI = 1.53 – 6.40; extended SCCS: IRR = 2.43, 95%CI = 1.11 – 5.33) compared with no association with the SCRIs (SCRI-pre: IRR = 0.60, 95%CI = 0.27 – 1.33; SCRI-post: IRR = 0.86, 95%CI = 0.34 – 2.19), although confidence intervals were wide. There was very good agreement between all designs for the unadjusted second dose analyses, confirming the known harmful association between the second dose of Moderna and Pfizer vaccines and myocarditis. Conclusions In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.
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Schultze et al. (2023) conducted an observational in Myocarditis (n=1,757). COVID-19 vaccines vs. Unexposed control periods was evaluated on Incidence of myocarditis (Moderna, standard SCCS) (IRR 3.12, 95% CI 1.53-6.40). Standard and extended self-controlled case series designs yielded harmful incidence rate ratios for the Moderna COVID-19 vaccine (IRR 3.12) compared to no association found using self-controlled risk interval designs.
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