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. 2022 Jul;45(7):765-780.
doi: 10.1007/s40264-022-01186-z. Epub 2022 Jun 23.

Signaling COVID-19 Vaccine Adverse Events

Rave Harpaz  1 , William DuMouchel  2 , Robbert Van Manen  2 , Alexander Nip  2 , Steve Bright  2 , Ana Szarfman  3 , Joseph Tonning  4 , Magnus Lerch  2   5
Affiliations

Signaling COVID-19 Vaccine Adverse Events

Rave Harpaz et al. Drug Saf. 2022 Jul.

Abstract

Introduction: Statistical signal detection is a crucial tool for rapidly identifying potential risks associated with pharmaceutical products. The unprecedented environment created by the coronavirus disease 2019 (COVID-19) pandemic for vaccine surveillance predisposes commonly applied signal detection methodologies to a statistical issue called the masking effect, in which signals for a vaccine of interest are hidden by the presence of other reported vaccines. This masking effect may in turn limit or delay our understanding of the risks associated with new and established vaccines.

Objective: The aim is to investigate the problem of masking in the context of COVID-19 vaccine signal detection, assessing its impact, extent, and root causes.

Methods: Based on data underlying the Vaccine Adverse Event Reporting System, three commonly applied statistical signal detection methodologies, and a more advanced regression-based methodology, we investigate the temporal evolution of signals corresponding to five largely recognized adverse events and two potentially new adverse events.

Results: The results demonstrate that signals of adverse events related to COVID-19 vaccines may be undetected or delayed due to masking when generated by methodologies currently utilized by pharmacovigilance organizations, and that a class of advanced methodologies can partially alleviate the problem. The results indicate that while masking is rare relative to all possible statistical associations, it is much more likely to occur in COVID-19 vaccine signaling, and that its extent, direction, impact, and roots are not static, but rather changing in accordance with the changing nature of data.

Conclusions: Masking is an addressable problem that merits careful consideration, especially in situations such as COVID-19 vaccine safety surveillance and other emergency use authorization products.

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Conflict of interest statement

The authors declare no conflict of interest. Rave Harpaz, William DuMouchel, Robbert Van Manen, Alexander Nip, Steve Bright, and Magnus Lerch are employed by Oracle Health Sciences, which provides the signal detection and management software used to conduct the research for this article.

Figures

Fig. 1
Fig. 1
The evolution of signal scores for Bell's palsy, myocarditis, pericarditis, and appendicitis. MGPS Multi-item Gamma Poisson Shrinker, RGPS Regression-Adjusted Gamma Poisson Shrinker, W week
Fig. 2
Fig. 2
The evolution of signal scores for pulmonary embolism, herpes zoster, and tinnitus. MGPS Multi-item Gamma Poisson Shrinker, RGPS Regression-Adjusted Gamma Poisson Shrinker, W week
See this image and copyright information in PMC

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