Signaling COVID-19 Vaccine Adverse Events

Harpaz, Rave; DuMouchel, William; Manen, Robbert Van; Nip, Alexander; Bright, S.; Szarfman, Ana; Tonning, Joseph M.; Lerch, Magnus

doi:10.1007/s40264-022-01186-z

Cited by 21 publications

(17 citation statements)

References 59 publications

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“…Disproportionality analysis was not feasible for the Dutch spontaneous reporting system due to the large volume of reported AEFIs for the COVID-19 vaccines and selective reporting for certain AEFI. 40,41,52 In conclusion, this Dutch CEM study found an incidence of menstrual disorders of 41.4 per 1000 female participants aged ≤54 years.…”

Section: Use Of Contraceptivesmentioning

confidence: 64%

Menstrual abnormalities after COVID‐19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient‐reported data

Duijster

Schoep

Nieboer

et al. 2023

Brit J Clinical Pharma

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AimsDuring the COVID‐19 vaccination campaigns, the number of reports of menstrual abnormalities increased rapidly. Here, we describe the nature and potential risk factors associated with menstrual abnormalities based on spontaneously reporting data as well as data from a prospective cohort event monitoring (CEM) study as these are poorly studied.MethodsReports of menstrual abnormalities received by the Netherlands Pharmacovigilance Centre Lareb in the spontaneous reporting system between February 2021 and April 2022 were summarized. In addition, logistic regression analysis was performed on the reported menstrual abnormalities in the CEM study to assess the association between person characteristics, prior SARS‐CoV‐2 infection and use of hormonal contraceptives and the occurrence of menstrual abnormalities after vaccination.ResultsWe analysed over 24 000 spontaneous reports of menstrual abnormalities and over 500 episodes (among 16 929 included women) of menstrual abnormalities in the CEM study. The CEM study showed an incidence of 41.4 per 1000 women aged ≤54 years. Amenorrhoea/oligomenorrhoea and heavy menstrual bleeding collectively accounted for about half of all abnormalities reported. Significant associations were observed for the age group 25–34 years (odds ratio 2.18; 95% confidence interval 1.45–3.41) and the Pfizer vaccine (odds ratio 3.04; 95% confidence interval 2.36–3.93). No association was observed for body mass index and presence of most comorbidities assessed.ConclusionThe cohort study showed a high incidence of menstrual disorders among women aged ≤54 years, and this observation was supported by the analysis of spontaneous reports. This suggests that a relation between COVID‐19 vaccination and menstrual abnormalities is plausible and should be further investigated.

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Section: Use Of Contraceptivesmentioning

confidence: 64%

Menstrual abnormalities after COVID‐19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient‐reported data

Duijster

Schoep

Nieboer

et al. 2023

Brit J Clinical Pharma

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“…Interestingly, in the US Vaccine Adverse Event Reporting System (VAERS), masking has been found to be rare overall, but more likely to affect COVID-19 vaccines than other vaccines, and regressionbased methodologies may help address the problem. 56 On generating near real-time, real-world evidence…”

Section: Lessons Learned On Facing a Massive Influx Of Spontaneous Re...mentioning

confidence: 99%

“…The large contribution of certain COVID‐19 vaccines to reports in EudraVigilance has an impact on reporting odds ratios for other COVID‐19 vaccines and other medicines, with signals being masked or false associations being flagged as potential signals. Interestingly, in the US Vaccine Adverse Event Reporting System (VAERS), masking has been found to be rare overall, but more likely to affect COVID‐19 vaccines than other vaccines, and regression‐based methodologies may help address the problem 56 …”

Section: Lessons Learnedmentioning

confidence: 99%

Safety Monitoring of COVID‐19 Vaccines: Perspective from the European Medicines Agency

Durand

Dogné

Cohet

et al. 2023

Clin Pharma and Therapeutics

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Prior to deployment of COVID‐19 vaccines in the European Union (EU) in 2021, a high vaccine uptake leading to an unprecedented volume of safety data from spontaneous reports and real‐world evidence, was anticipated. The European Medicines Agency (EMA) implemented specific activities to ensure enhanced monitoring of emerging vaccine safety information, including intensive monitoring of reports of adverse events of special interest (AESIs) and the use of observed‐to‐expected (O/E) analyses. EMA also commissioned several independent observational studies using a large network of electronic healthcare databases and primary data collection via mobile and web‐based applications. This preparedness was key for two high‐profile safety signals: thrombosis with thrombocytopenia syndrome (TTS), a new clinical entity associated with adenovirus‐vectored vaccines, and myocarditis/pericarditis with messenger RNA (mRNA) vaccines. With no existing case definition nor background rates, the signal of TTS posed particular challenges. Nevertheless, it was rapidly identified, evaluated, contextualised and the risk minimised thanks to close surveillance and an efficient use of available evidence, clinical expertise and flexible regulatory tools. The two signals illustrated the complementarity between spontaneous and real‐world data, the former enabling rapid risk identification and communication, the latter enabling further characterisation. The COVID‐19 pandemic has tremendously enhanced the development of tools and methods to harness the unprecedented volume of safety data generated for the vaccines. Areas for further improvement include the need for better and harmonised data collection across Member States (e.g., stratified vaccine exposure) to support signal evaluation in all population groups, risk contextualisation and safety communication.

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“…With the rapid increase of submitted ICSRs however, the signal detection process adopted other quantitative approaches as well in order to handle the large datasets. Disproportionality analysis, using reporting odds ratios, was deemed less useful during the large‐scaled COVID‐19 vaccination campaign due to issues like statistical masking effect 21 …”

Section: Introductionmentioning

confidence: 99%

“…Disproportionality analysis, using reporting odds ratios, was deemed less useful during the large-scaled COVID-19 vaccination campaign due to issues like statistical masking effect. 21 In addition, since vaccination campaigns included a large part of the population, the numbers of a reported specific adverse reaction should be placed in perspective with background incidence rates of these clinical events became in assessing whether an association with the suspect drug is plausible. In May 2020, the ACCESS (The vACCine Covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines.…”

Section: Introductionmentioning

confidence: 99%

Observed‐over‐Expected analysis as additional method for pharmacovigilance signal detection in large‐scaled spontaneous adverse event reporting

Boom

Eekeren

Hunsel

2023

Pharmacoepidemiology and Drug

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Background The large‐scale COVID‐19 vaccination campaigns in 2021 and 2022 led to a rapid increase in numbers of received adverse event reports in spontaneous reporting systems. As background incidences of naturally occurring medical events became increasingly relevant for causality assessment of potential associations with the vaccines, a novel approach for signal detection was warranted. Objectives This article illustrates the Observed‐over‐Expected (O/E) analysis as an additional method for signal detection and risk assessment in large‐scaled spontaneous reporting systems. Methods All individual case safety reports (ICSRs) concerning idiopathic peripheral facial paralysis or Bell's palsy following administration of the COVID‐19 vaccines (n = 291) manufactured by Pfizer/BioNTech (Comirnaty), Moderna (Spikevax), AstraZeneca (Vaxzevria) and Janssen (JCOVDEN) received by the National Pharmacovigilance Centre Lareb until 24th March 2022 were included in the O/E analysis, within a risk window of 7 and 14 days following immunisation. Dutch background incidence rates from 2019 and exposure of the Dutch population to the vaccines were obtained from the PHARMO institute and RIVM. The data was stratified in age groups, gender and administered dose in order to differentiate between population subgroups. Results Bell's palsy was reported more frequently than expected in several population subgroups following administration of all four COVID‐19 vaccines, including children and adolescents. Among children, a high O/E ratio was found for boys aged 5–14 years after receiving the Pfizer/BioNTech vaccine. Regarding adolescents and young adults, women aged 15–24 years receiving Pfizer/BioNTech and Moderna, and men aged 15–24 years receiving Janssen developed Bell's palsy more often than expected. Furthermore, O/E ratios were high for individuals aged 25–64, regarding females receiving Pfizer, Moderna and AstraZeneca and males receiving Janssen. As facial paralysis was not labelled as an adverse event for the Janssen vaccine, this analysis contributed to signalling the association and warranting further regulatory action. Conclusions The O/E method is a useful approach for signal detection of potential adverse reactions when handling large numbers of ICSRs. Further research is needed to attest to the causality on a clinical basis.

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Signaling COVID-19 Vaccine Adverse Events

Cited by 21 publications

References 59 publications

Menstrual abnormalities after COVID‐19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient‐reported data

Menstrual abnormalities after COVID‐19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient‐reported data

Safety Monitoring of COVID‐19 Vaccines: Perspective from the European Medicines Agency

Observed‐over‐Expected analysis as additional method for pharmacovigilance signal detection in large‐scaled spontaneous adverse event reporting

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