Establishing the Vaccine Safety Health Link: A large, linked data resource for the investigation of vaccine safety concerns.

OBJECTIVE: Post-licensure vaccine safety surveillance of adverse events following immunisation is critical to ensure public safety and confidence in vaccines. This paper aims to describe the governance structure and data linkage methodology behind the establishment of the largest linked vaccine safety surveillance data resource in Australia - The Vaccine Safety Health Link (VSHL). METHODS: The Vaccine Safety Health Link contains linked records from the Australian Immunisation Register with records from hospital, perinatal, mortality, and notifiable disease datasets in near real-time. Linkage is done by the Centre for Victorian Data Linkage who receive the datasets in an identifiable format which then undergo standardisation, enrichment, linkage, quality assurance and de-identification, prior to being supplied for analysis. RESULTS: The VSHL data resource allows sensitive and rapid analysis of a broad spectrum of suspected adverse events to ensure the safety of all vaccines administered. It is also used to refute spurious concerns where no associations are found, upholding trust, and maintaining vaccine confidence. CONCLUSIONS: The Vaccine Safety Health Link's surveillance design complements existing vaccine safety surveillance methods. Challenges encountered and lessons learnt using Vaccine Safety Health Link would benefit linkage projects globally. IMPLICATIONS FOR PUBLIC HEALTH: In its first two years, The Vaccine Safety Health Link has been used for 14 vaccine safety investigations. Studies into these conditions would not have otherwise been possible. The Vaccine Safety Health Link also partners with the Global Vaccine Data Network™ for approved collaborative studies with a combined population of over 300 million people.

Laboratory-confirmed respiratory viral infection triggers for acute myocardial infarction and stroke: Systematic review protocol.

BACKGROUND: Cardiovascular disease contributes substantially to global mortality and morbidity. Respiratory tract infections, particularly influenza, may trigger an increase in the short-term risk of acute myocardial infarction (AMI) and stroke. Recent studies have also linked this risk to other respiratory viruses, including respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pathogen-specific relative contributions, the strength of their associations, and overall public health significance are poorly understood. Assuming causal links, understanding, quantifying, and comparing the effects of different pathogens as triggering factors for acute cardiovascular events is critical to guide future research and prevention. Our aim is to conduct a systematic review to examine the relative effects of laboratory-confirmed respiratory virus infections as triggers for acute myocardial infarction and stroke. METHODS: We will conduct a comprehensive search of Ovid MEDLINE, PubMed, Ovid Embase, Cochrane Library Central Register of Controlled Trials, and Web of Science, from inception to the end of March 2024. Studies capturing respiratory viral infection(s) using laboratory-confirmatory methods, incidence of AMI or stroke (ischaemic or haemorrhagic), and those involving human participants in any country, will be assessed for eligibility. We will include the following analytical epidemiological study types: randomised controlled trials, cohort and case-control studies, self-controlled case series, and case-crossover designs. We will not impose restrictions on the date, language, study population, geographical region, or sample size, to minimise the risk of introducing biases. Search results will be screened for eligibility by two independent reviewers, and discrepancies resolved by consensus and/or arbitration by a third reviewer. We will assess the risk of bias among the included studies by adopting the Cochrane Collaboration tools for randomised and non-randomised studies. The overall quality of studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will examine sources of heterogeneity, and if studies are sufficiently homogeneous, a meta-analysis will be conducted to calculate the pooled effect sizes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024494997.

Audiovestibular adverse events following COVID-19 vaccinations.

INTRODUCTION: Evidence regarding audiovestibular adverse events post COVID-19 vaccination to date has been inconclusive regarding a potential association. This study aimed to determine if there was an increase in audiovestibular events following COVID-19 vaccination in South-eastern Australia during January 2021-March 2023. METHODS: A multi-data source approach was applied. First, a retrospective observational analysis of spontaneous reports of audiovestibular events to a statewide vaccine safety surveillance service, SAEFVIC. Second, a self-controlled case series analysis using general practice data collected via the POpulation Level Analysis and Reporting (POLAR) tool. RESULTS AND CONCLUSIONS: This study is the first to demonstrate an increase in general practice presentations of vertigo following mRNA vaccines (RI = 1.40, P <.001), and tinnitus following both the Vaxzevria® adenovirus vector and mRNA vaccines (RI = 2.25, P <.001 and 1.53, P <.001 respectively). There was no increase in hearing loss following any COVID-19 vaccinations. Our study, however, was unable to account for the potential of concurrent COVID-19 infections, which literature has indicated to be associated with audiovestibular events. Healthcare providers and vaccinees should be alert to potential audiovestibular complaints after COVID-19 vaccination. Our analysis highlights the importance of using large real-world datasets to gather reliable evidence for public health decision making.

What would have happened anyway? Population data source considerations when estimating background incident rates of adverse events following immunisation to inform vaccine safety.

INTRODUCTION: Understanding background incident rates of adverse events following immunisation (AEFI) is essential to rapidly detect, evaluate, respond to, and communicate about vaccine safety concerns, especially for new vaccines. Creating estimates based on geographic specific population level data is increasingly important, as new AEFI presentations will be subject to the same local influences of population demography, exposures, health system variations and level of health care sought. METHODS: We conducted a retrospective cohort analysis of hospital admissions, emergency department presentations and general practice consultations from 2015 to 2019-before introduction of COVID-19, Mpox or Shingrix vaccination-to estimate background incident rates for 37 conditions considered potential AEFI of special interest (AESI). Background incident rates per 100,000 population were calculated and presented as cases expected to occur coincidentally 1 day, 1 week and 6 weeks post-vaccination, by life-stage age-groups and presenting healthcare setting. We then assessed the proportional contribution of each data source to inform each AESI background rate estimate. RESULTS: 16,437,156 episodes of the 37 AESI were identified. Hospital admissions predominantly informed 19 (51%) of AESI, including exclusively ADEM and CVST; 8 AESI (22%) by primary care, and 10 (27%) a mix. Four AESI (allergic urticaria, Bell's palsy, erythema multiform and sudden death) were better informed by emergency presentations than admissions, but conversely 11 AESI (30%) were not captured in ICD-10 coded emergency presentations at all. CONCLUSIONS: Emergent safety concerns are inevitable in population-wide implementation of new vaccines, therefore understanding local background rates aids both safety signal detection as well as maintaining public confidence in vaccination. Hospital and primary care data sources can be interrogated to inform expected background incident rates of adverse events that may occur following vaccination. However, it is necessary to understand which data-source provides best intelligence according to nature of condition and presenting healthcare setting.