Reference set for performance testing of pediatric vaccine safety signal detection methods and systems

BackgroundSafety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources.MethodsThe study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement.ResultsWe selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC.ConclusionA reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.     

Translating vaccine policy into action: A report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life.     

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5–9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2–27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7–157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4–90.3), and Enders’Edmonston (IRR: 8.5; 95% CI: 1.9–38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3–87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs.     

珠海市西部地区2010—2012年疑似预防接种异常反应监测分析

目的分析珠海市西部地区2010—2012年疑似预防接种异常反应（AEFI）发生情况及监测系统运转情况,评价监测系统运转灵敏性及预防接种疫苗的安全性。方法通过疑似预防接种异常反应信息管理系统,收集整理珠海市西部地区2010—2012年报告的AEFl个案,采用描述性方法对相关指标进行分析。结果珠海市西部地区2010—2012年共报告AEFl个案103例,发生率为11．47／10万。AEFl个案以一般反应为主,共72例,占69．90％,异常反应27例,占26．21％,偶合症3例,占2．91％,心因性反应1例,占0．97％。结论AEFI监测系统运转情况良好,预防接种服务质量和疫苗的安生性较高。     

Economic evaluation of meningococcal serogroup B childhood vaccination in Ontario,Canada

Objective

Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective.

Methods

A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n = 150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%.

Results

A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine-associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust.

Conclusions

An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions.     

各国疫苗Ⅳ期临床监管对我国的借鉴意义

目的：为我国疫苗Ⅳ期临床监管提供可行性建议。方法：利用文献搜集法,通过对美国、澳大利亚、日本、加拿大等具有疫苗Ⅳ期临床监管成功经验国家的特点进行分析总结,再结合我国疫苗监管实际情况,提出建议。结果与结论：国外Ⅳ期临床监管在数据库建设、专家队伍、信息反馈等方面具有强大优势,我国可学习借鉴。     

Acceptability of Internet adverse event self-reporting for pandemic and seasonal influenza immunization among health care workers

This study assessed the acceptability and feasibility of Internet self-reporting for adverse events following pandemic and seasonal influenza immunization among 270 health care workers at a tertiary care children's and women's hospital in fall 2009. Participants responded to an online questionnaire 72 h after vaccine receipt. Non-responders were sent a reminder email 8–10 days after vaccine receipt, followed by a telephone call for those who did not respond online. The overall online response rate was high (88%). Participants rated the online self-report easy to use and would be willing to use it again. The high response rate and acceptability of the online report method suggest that web-based self-reporting for adverse event following immunization (AEFI) has the potential for rapid assessments of AEFI in mass or new immunization programs.     

常熟市2008年疑似预防接种异常反应的监测和评价

目的了解常熟市预防接种后不良反应的发生情况,客观评价疫苗免疫的安全性,以制定科学免疫策略。方法对常熟市2008年发生的疑似预防接种异常反应进行分析。结果2008年报告疑似预防接种异常反应258例中一般反应201例,占84．45％;异常反应35例,占14．71％;偶合症2例,占0．84％。报告发生反应的疫苗品种共15种,各种疫苗总AEFI发生率为71．09／10万,全细胞百白破、无细胞百白破的疑似预防接种异常反应发生率最高,分别为546．45／10万和333．66／10万。结论在实施接种前,应当告知受种者或者其监护人所接种疫苗的品种、作用、禁忌、不良反应以及注意事项,询问受种者的健康状况以及是否有接种禁忌等情况,并如实记录告知和询问情况。加强预防接种门诊规范化建设、增加人员配备和强化预防接种规范操作。     

Vaccine adverse event reporting system (VAERS): Evaluation of 31 years of reports and pandemics’ impact

BackgroundVaccine adverse event reporting system (VAERS) was established in the United States (U.S.) as an early warning system with a main purpose of collecting post-marketing Adverse events following immunizations (AEFIs) reports to monitor the vaccine safety and to mitigate the risks from vaccines. During the coronavirus diseases 2019 (COVID-19) pandemic, VAERS got more attention as its important role in monitoring the safety of the vaccines. The aim of this study was to investigate VAERS patterns, reported AEFI, vaccines, and impact of different pandemics since its inception.MethodsThis was an observational study using VARES data from 2/7/1990 to 12/11/2021. Patterns of reports over years were first described, followed by a comparison of reports statistics per year. Furthermore, a comparison of incidents (death, ER visits, etc.) statistics over years, in addition to statistics of each vaccine were calculated. Moreover, each incident's statistics for each vaccine were calculated and top vaccines were reported. All analyses were conducted using R (Version 1.4.1717) and Excel for Microsoft 365.ResultsThere were 1,396,280 domestic and 346,210 non-domestic reports during 1990–2021, including 228 vaccines. For both domestic and non-domestic reports, year of 2021 had the highest reporting rate (48.52 % and 70.33 %), in addition a notable change in AEFIs patterns were recorded during 1991, 1998, 2000, 2006, 2009, 2011, and 2017. AEFIs were as follow: deaths (1.00 % and 4.08 %), ER or doctor visits (13.37 % and 2.27 %), hospitalizations (5.84 % and 27.78 %), lethal threat (1.42 % and 4.38 %), and disabilities (1.4 % and 7.96 %). Pyrexia was the top reported symptom during the past 31 years, except for 2021 where headache was the top one. COVID-19 vaccines namely Moderna, Pfizer-Biontech, and Janssen were the top 3 reported vaccines with headache, pyrexia, and fatigue as the top associated AEFIs. Followed by Zoster, Seasonal Influenza, Pneumococcal, and Human papillomavirus vaccines.ConclusionsThe large data available in VARES make it a useful tool for detecting and monitoring vaccine AEFIs. However, its usability relies on understating the limitations of this surveillance system, the impact of governmental regulations, availability of vaccines, and public health recommendations on the reporting rate.     

上海市青浦区2010年疑似预防接种异常反应监测分析

目的分析上海市青浦区2010年疑似预防接种异常反应(AEFI)的发生情况,评价AEFI监测系统运行状况及预防接种安全性。方法采用描述性流行病学方法对2010年青浦区AEFI监测资料进行分析。结果 2010年青浦区共报告AEFI475例,其中一般反应447例(94.11%),异常反应12例(2.53%),偶合症16例(3.37%);48h内报告率、48h内流调率为100.00%;<1岁的212例(44.63%);较多分布在4～9月(65.68%)。475例AEFI以发热(64.71%)和局部红肿(16.56%)为主,94.74%发生在接种疫苗1天内。报告发生AEFI病例数较多的疫苗为白百破疫苗(140例)、A群流脑疫苗(114例)和麻疹疫苗(50例);报告发生率较高的疫苗为A群流脑疫苗(441.38人次/10万剂)、白百破疫苗(303.83人次/10万剂)和肺炎疫苗(262.70人次/10万剂)。475例AEFI中,治愈433例(91.16%),好转40例(8.42%)。结论 AEFI发生率与多种因素有关。开展监测时,对不同人群、不同时间和不同疫苗的关注应有侧重点。注重沟通,加强人员配备及培训,强化预防接种规范操作。