Causality assessment of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)

Adverse events following immunization (AEFI) reported to the national Vaccine Adverse Event Reporting System (VAERS) represent true causally related events, as well as events that are temporally, but not necessarily causally related to vaccine.     

Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)

The Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) conduct post-licensure vaccine safety monitoring using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous (or passive) reporting system. This means that after a vaccine is approved, CDC and FDA continue to monitor safety while it is distributed in the marketplace for use by collecting and analyzing spontaneous reports of adverse events that occur in persons following vaccination. Various methods and statistical techniques are used to analyze VAERS data, which CDC and FDA use to guide further safety evaluations and inform decisions around vaccine recommendations and regulatory action. VAERS data must be interpreted with caution due to the inherent limitations of passive surveillance. VAERS is primarily a safety signal detection and hypothesis generating system. Generally, VAERS data cannot be used to determine if a vaccine caused an adverse event. VAERS data interpreted alone or out of context can lead to erroneous conclusions about cause and effect as well as the risk of adverse events occurring following vaccination. CDC makes VAERS data available to the public and readily accessible online.We describe fundamental vaccine safety concepts, provide an overview of VAERS for healthcare professionals who provide vaccinations and might want to report or better understand a vaccine adverse event, and explain how CDC and FDA analyze VAERS data. We also describe strengths and limitations, and address common misconceptions about VAERS. Information in this review will be helpful for healthcare professionals counseling patients, parents, and others on vaccine safety and benefit-risk balance of vaccination.     

Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early detection of intussusception and other events after rotavirus vaccination

The Vaccine Adverse Event Reporting System (VAERS) is the US passive surveillance system monitoring vaccine safety. A major limitation of VAERS is the lack of denominator data (number of doses of administered vaccine), an element necessary for calculating reporting rates. Empirical Bayesian data mining, a data analysis method, utilizes the number of events reported for each vaccine and statistically screens the database for higher than expected vaccine-event combinations signaling a potential vaccine-associated event. This is the first study of data mining in VAERS designed to test the utility of this method to detect retrospectively a known side effect of vaccination–intussusception following rotavirus (RV) vaccine. From October 1998 to December 1999, 112 cases of intussusception were reported. The data mining method was able to detect a signal for RV-intussusception in February 1999 when only four cases were reported. These results demonstrate the utility of data mining to detect significant vaccine-associated events at early date. Data mining appears to be an efficient and effective computer-based program that may enhance early detection of adverse events in passive surveillance systems.     

医疗安全不良事件主动报告系统的设计与实现

本文主要介绍医疗安全不良事件报告系统的总体设计思路、实现方法及主要功能。医疗安全不良事件报告系统的实施对于医院内部防范医疗差错、减少医疗事故提供流程化、规范化的技术手段,为提高医院管理水平、促进医疗服务质量的改善提供支持。     

Post-licensure surveillance of trivalent adjuvanted influenza vaccine (aIIV3; Fluad), Vaccine Adverse Event Reporting System (VAERS), United States,July 2016–June 2018

Background

Trivalent adjuvanted influenza vaccine (aIIV3; Fluad®) was approved in the United States (U.S.) in 2015 for adults aged ≥65?years and has been in use since the 2016–17 influenza season.

医疗不良事件报告系统的设计与应用

目的设计科学合理的医疗不良事件报告系统,建立全面的、统一的医疗不良事件标准分类系统和患者安全术语,使不良事件上报管理更加标准化和科学化。方法通过借鉴国内外医疗不良事件报告系统的先进经验,本系统对医疗不良事件从类型、原因、对患者的影响、事后处理、原因分析等项目均设置了大量统一、规范的预设项,报告输入时采用选择题式和简单的描述性语言即可完成不良事件的上报。结论应用医疗不良事件报告系统后,不仅简化了医务人员工作量,提高了不良事件上报率,而且便于管理者对不良事件进行不同角度和纬度的统计分析,采取改进措施,避免类似事件的再次发生。     

Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System

BackgroundIn October 2012, the Advisory Committee on Immunization Practices (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's prior history of receiving Tdap. A retrospective cohort study to assess the safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD) sites during 2010–2012 found a small but statistically significant increased risk of chorioamnionitis.ObjectiveWe conducted a review of the VAERS database to describe reports of chorioamnionitis following receipt of any vaccines.MethodsWe searched the VAERS database for reports of chorioamnionitis after any vaccine in the United States during the period from July 1, 1990 through February 2, 2014.ResultsVAERS received 31 reports of chorioamnionitis out of 3389 pregnancy reports in 24 years. The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported.ConclusionChorioamnionitis was found to be uncommonly reported, representing 1% of pregnancy reports to VAERS. A majority of reports had at least one risk factor for chorioamnionitis.     

Safety of 9-valent human papillomavirus vaccine administration among pregnant women: Adverse event reports in the Vaccine Adverse Event Reporting System (VAERS), 2014–2017

Introduction

9-valent human papillomavirus vaccine (9vHPV) was approved by the Food and Drug Administration (FDA) in December 2014. 9vHPV is not recommended during pregnancy, but some women of childbearing age may be inadvertently exposed. This study aims to evaluate reports submitted to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women exposed to 9vHPV.

开展医疗器械不良事件监测和报告工作的探讨

开展医疗器械不良事件监测和报告工作是十分重要的。本文介绍了医疗器械不良事件产生的原因、监测的意义,并对我院在该领域开展相关工作的具体方法措施等进行了探讨。     

Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS)

BackgroundThe objective of this study is to assess cases of thrombocytopenia, including immune thrombocytopenia (ITP), reported to the Vaccine Adverse Event Reporting System (VAERS) following vaccination with mRNA COVID-19 vaccines.MethodsThis case-series study analyzed VAERS reports of thrombocytopenia after vaccination with Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine.ResultsFifteen cases of thrombocytopenia were identified among 18,841,309 doses of Pfizer-BioNTech COVID-19 Vaccine and 13 cases among 16,260,102 doses of Moderna COVID-19 Vaccine. The reporting rate of thrombocytopenia was 0.80 per million doses for both vaccines. Based on an annual incidence rate of 3.3 ITP cases per 100,000 adults, the observed number of all thrombocytopenia cases, which includes ITP, following administration of mRNA COVID-19 vaccines is not greater than the number of ITP cases expected.ConclusionsThe number of thrombocytopenia cases reported to VAERS does not suggest a safety concern attributable to mRNA COVID-19 vaccines at this time.     

Thrombocytopenia after vaccination: case reports to the US Vaccine Adverse Event Reporting System, 1990-2008

We reviewed thrombocytopenia (TP) reports to the US Vaccine Adverse Event Reporting System (VAERS). We examined TP patterns for differences in single versus multiple immunization reports, presence of a live viral vaccine, seriousness, age, and interval to symptom onset. We found 1510 reports of possible TP and after exclusions evaluated 1440 for possible causes. Most (1078; 75%) met the regulatory definition of a serious adverse event. TP was reported after inactivated and live viral vaccines. Platelet counts <10 × 10⁹/L were reported. Identified vaccines could be prioritized for hypothesis-testing studies.     

Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007

During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted.     

Adverse events following a third dose of measles,mumps, and rubella vaccine in a mumps outbreak

During a 2009–2010 mumps outbreak in a New York State village, a third dose of measles, mumps, and rubella (MMR) vaccine was administered to children in three schools as a control measure. Information on local and systemic adverse events (AE) was collected by a self-report survey distributed to all children in grades 6–12. A comprehensive search for AE following MMR vaccination was conducted using physician records and the Vaccine Adverse Events Reporting System (VAERS). A literature search was performed for published reports pertaining to AE associated with mumps-containing vaccine, using the Jeryl-Lynn strain, from 1969 to 2011. A total of 1755 individuals received the third dose; 1597 (91.0%) returned the survey. Of those, 115 (7.2%) reported at least one local or systemic AE in the 2 weeks following vaccination. The most commonly reported AE were “pain, redness, or swelling at the injection site” (3.6%) and “joint or muscle aches” (1.8%). No serious AE were reported in the survey, physician records or through VAERS. The proportions of AE found in the present study were lower than or within the range of those reported in prior studies of first- and second-dose MMR vaccine studies. The results of this study suggest that a third dose of MMR vaccine administered in an outbreak setting is safe, with injection site reactions reported more frequently than systemic reactions. However, to assess risk for rare or serious AE after a third dose of MMR vaccine, longer term studies would be required.     

Elective termination of pregnancy after vaccination reported to the Vaccine Adverse Event Reporting System (VAERS): 1990-2006

Generally, live-virus vaccines are contraindicated for pregnant women because of the theoretical risk of transmission of the vaccine virus to the fetus. Advisory groups recommend avoiding pregnancy in the immediate period after administration of such contraindicated vaccines (CVs) and stress benefit-to-risk evaluation for live or inactivated vaccines regarding pregnancy. Given the limited available data and theoretical risks associated particularly with live-virus vaccines, inadvertent immunization with CVs may lead to elective termination of pregnancy (ETP), despite advisory group statements that "vaccination is not ordinarily an indication to terminate the pregnancy." The Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system managed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), accepts reports of adverse events after vaccination. The objectives of this review were to describe reports of ETP in VAERS and characterize the circumstances of inadvertent administration of vaccines to pregnant women among ETP reports. We reviewed VAERS reports of ETP submitted from 1990 to 2006. Reports of ETP for reasons other than vaccination during or shortly before pregnancy, such as fetal abnormalities or deaths, were excluded. Of 80 ETP reports, 62 (78%) originated from the US; 79 (99%) were reported by manufacturers. Median age of vaccinees was 26 years (range: 13-43 years; 67 reports). Seventy-three vaccinees (91%) received a single vaccine; 65 (81%) received at least one live-virus vaccine. In 48 (60%) ETP reports, vaccinees were unaware of pregnancy at time of immunization. In 15 (19%) reports, vaccinees became pregnant within 3 months of vaccination; in 13 (16%) reports, vaccinees might have been pregnant before vaccination; in 4 (5%) reports, information was missing. All 80 reports of ETP involved vaccines for which possible effects on fetal development are unknown. However, no cases of vaccine-associated congenital rubella or varicella syndromes have been reported in the medical literature. Also, these syndromes have not been reported to varicella or rubella vaccine pregnancy registries. VAERS has the limitations of passive surveillance systems. Under-reporting of ETP in VAERS could be substantial. More attention may be needed to assess the likelihood of pregnancy when administering vaccines to women with child-bearing potential, and to inform women who learn they are pregnant shortly after being immunized of current information on risks. Quantifying the frequency of ETP related to CVs and the risk (if any) to the fetus of such vaccines can help to inform policy, practice, and individual decision making. Good quality information may be obtained from controlled observational studies.     

我国医疗不良事件报告系统研究与应用现状述评

医疗不良事件报告是防范医疗不良事件重复发生、提高医疗质量的一个重要措施.从我国医疗不良事件报告系统的政策和制度入手,对我国现有医疗不良事件报告系统进行概述和分析,总结其特点与缺陷,并对完善我国医疗不良事件报告系统提出了展望.     

Adverse events after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine administered to adults 65 years of age and older reported to the Vaccine Adverse Event Reporting System (VAERS), 2005-2010

Background

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was not licensed for use in adults aged ≥65 years due to lack of sufficient efficacy and safety data.

Objective

To characterize reports to the Vaccine Adverse Event Reporting System (VAERS) among adults aged ≥65 years who received Tdap vaccine ‘off-label’ to assess for potential vaccine safety concerns.

Methods

We searched VAERS for US reports of adverse events (AEs) in subjects aged ≥65 years who received Tdap vaccine from 9/1/2005 to 9/08/2010. Medical records were requested for all reports coded as serious (death, hospitalization, prolonged hospitalization, permanent disability, life-threatening-illness). Proportional reporting ratio (PRR) was used to assess for higher proportionate reporting for AEs after Tdap compared with Td reports in subjects aged ≥65 years.

Results

VAERS received 243 reports following Tdap administered to persons aged ≥65 years. Eleven (4.5%) reports were serious, including two deaths. Most common AEs were local reactions in 100 (41.2%) reports. Seventy-eight (32.1%) reports contained coding terms that denoted inappropriate administration of vaccine. ‘Cough’ was the only term associated with disproportionately higher reporting after Tdap compared with Td. Six of seven Tdap reports containing the term ‘Cough’ were non-serious. Clinical review of serious reports identified no unusual patterns of AEs.

Conclusion

Our VAERS review of the ‘off-label’ use of Tdap vaccine in adults ≥65 years did not find any safety concerns that warrant further study. These data will provide useful baseline information to assist CDC and FDA with monitoring efforts as permissive recommendations for Tdap in older persons are adopted.     

综合医院医疗不良事件报告的障碍因素以及改进策略分析

医疗不良事件的分析总结对保证医疗质量起着促进作用,而报告医疗不良事件存在着许多障碍.通过调查湖北省、江苏省、浙江省12家医院的医疗不良事件的报告情况,分析阻碍医疗不良事件报告的原因,并提出相应建议.     

Postmarketing safety surveillance of trivalent recombinant influenza vaccine: Reports to the Vaccine Adverse Event Reporting System

On January 16, 2013, the Food and Drug Administration approved recombinant hemagglutinin influenza vaccine (RIV3) (Spodoptera frugiperda cell line; Flublok), which is the first completely egg-free flu vaccine licensed in the United States. To improve our understanding of the safety profile of this vaccine, we reviewed and summarized reports to the Vaccine Adverse Event Reporting System (VAERS) following RIV3. Through June 30, 2016, VAERS received 88 reports. Allergic reactions, including anaphylaxis, were the most common type of adverse event. Based on medical review, 10 cases met the Brighton Collaboration case definition of anaphylaxis, 21 reports described allergic reactions other than anaphylaxis, and 11 reports described signs and symptoms that suggested hypersensitivity. Other adverse events included injection site reactions, fatigue, myalgia, headache, and fever. The occurrence of anaphylaxis and other allergic reactions in some individuals may reflect an underlying predisposition to atopy that may manifest itself after an exposure to any drug or vaccine, and it does not necessarily suggest a causal relationship with the unique constituents that are specific to the vaccine product administered. Further research may elucidate the mechanism of allergic reactions following influenza vaccination: it is possible that egg proteins and influenza hemagglutinin play little or no role. Vaccination remains the single best defense against influenza and its complications. The information summarized here may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies.     

医疗器械安全(不良)事件管理中PDCA的应用研究

以医疗器械安全(不良)事件管理中PDCA的应用研究为重点进行阐述,结合当下医疗器械安全(不良)事件管理现状为主要依据,从计划环节、实行环节、检查环节、处理环节这几方面进行深入探索与研究,目的在于提升医疗器械安全(不良)事件管理中PDCA的应用效率。     

Vaccination of persons allergic to latex: a review of safety data in the Vaccine Adverse Event Reporting System (VAERS)

Vaccine products currently licensed in the US and other countries are marketed in vials and syringes that may contain natural latex allergens. Little scientific information exists regarding the safety of vaccination of latex-allergic individuals. A review of data within the Vaccine Adverse Event Reporting System (VAERS), a large registry of reported possible vaccine adverse reactions was conducted. A search of the database, which contains >160,000 vaccine adverse event reports, revealed only 28 cases of possible immediate-type hypersensitivity reactions in vaccine recipients with a history of allergy to latex. Given the large number of immunizations administered every year in the US, the reported risk of allergic reactions possibly due to latex contamination of vaccines appears to be very small.