A review of the Vaccine Adverse Event Reporting System database

The Vaccine Adverse Event Reporting System (VAERS) is an epidemiological database that has been maintained by the FDA and Centers for Disease Control and Prevention (CDC) since 1990. Authors from the National Immunization Programme of the CDC have previously described an epidemiological technique to make qualitative and quantitative measurement in the VAERS database. Application of this technique by ourselves (with further refinements and additions) have resulted in numerous publications showing the VAERS database has good positive predictive value in evaluating vaccine safety concerns that are compatible with observations by many other authors who have analysed different databases. In conclusion, VAERS studies will be particularly critical in the evaluation of the safety of many new or radically changed vaccines expected to be introduced in the relative near future.     

Development of the Vaccine Analytic Unit's research agenda for investigating potential adverse events associated with anthrax vaccine adsorbed

PURPOSE: In 2002, the Centers for Disease Control and Prevention established the Vaccine Analytic Unit (VAU) in collaboration with the Department of Defense (DoD). The focus of this report is to describe the process by which the VAU's anthrax vaccine safety research plan was developed following a comprehensive review of these topics. METHODS: Public health literature, surveillance data, and clinical sources were reviewed to create a list of adverse events hypothesized to be potentially related to anthrax vaccine adsorbed (AVA). From this list, a consensus process was used to select 11 important research topics. Adverse event background papers were written for each of these topics, addressing predetermined criteria. These were independently reviewed and ranked by a National Vaccine Advisory Committee (NVAC) workgroup. The adverse events included in the final priority list will be the subject of observational or other post marketing surveillance studies using the Defense Medical Surveillance System (DMSS) database. RESULTS: A review of various information sources identified over 100 potential adverse events. The review process recommended 11 topics as potentially warranting further study. The NVAC workgroup identified the following adverse event topics for study: arthritis, optic neuritis, and Stevens-Johnson syndrome/Toxic epidermal necrolysis. Two additional topics (systemic lupus erythematosus (SLE) and multiple, near-concurrent military vaccinations) were added in response to emerging public health and military concerns. CONCLUSIONS: The experience described, while specific for establishing the VAU's research agenda for the safety of the current anthrax vaccine, may be useful and adapted for research planning in other areas of public health research.     

An overview of adverse events reported by participants in CDC's anthrax vaccine and antimicrobial availability program

PURPOSE: The CDC's Anthrax Vaccine and Antibiotic Availability Program was implemented under an Investigational New Drug (IND) application to provide additional post-exposure prophylaxis for individuals potentially exposed to Bacillus anthracis in the fall of 2001. Participants were provided with two options: (1) 40 additional days of antimicrobial prophylaxis (i.e., ciprofloxacin, doxycycline, or amoxicillin); or (2) 40 additional days of antimicrobial prophylaxis plus three doses of anthrax vaccine adsorbed (AVA). METHODS: Participants were monitored for adverse events (AEs). Participants were asked to complete 2-week AE diaries for 6 weeks post-enrollment, and approximately 2 months after enrollment, active surveillance was conducted through telephone interviews with 1113 (64%) participants. RESULTS: A total of 1727 of approximately 10 000 previously prophylaxed persons enrolled to receive 40 additional days of antibiotics. Of these, 199 opted at enrollment to receive three doses of AVA in addition to the additional 40 days of antibiotic. Overall, 28% of participants reported at least one AE on their diaries. Results varied by surveillance mechanism, the diary data indicated differences in the proportion reporting AEs between participants receiving antibiotic only and participants receiving antibiotic and AVA. However, during the active 2-month telephone follow-up, the rates of AEs reported for both the antibiotic only and antibiotic plus AVA treatment regimens were similar. Additionally, ciprofloxacin and doxycycline had similar AE profiles, with only rigors reported significantly more often among ciprofloxacin recipients. CONCLUSIONS: Overall, the rates of AEs experienced by all participants were acceptable given the seriousness of potential B. anthracis exposure.     

Assessment of anthrax vaccination data in the Defense Medical Surveillance System, 1998-2004

PURPOSE: Understanding the completeness and accuracy of U.S. military anthrax vaccination data is important to the design and interpretation of studies to assess the safety of anthrax vaccine. We estimated the agreement between electronically recorded anthrax vaccination data in the Defense Medical Surveillance System (DMSS) versus anthrax vaccination data abstracted from hardcopy medical charts in a representative sample of the U.S. military from 1998 to 2004. METHODS: Medical chart abstractions were conducted at 28 military treatment facilities for 4201 personnel. Abstracted anthrax vaccination data for 1817 personnel, representing 7400 anthrax vaccine doses, were compared with electronically captured data in the DMSS from 1998 to 2004. Sensitivity, positive predictive value (PPV), specificity and negative predictive value (NPV) were calculated using weighted analyses. RESULTS: Weighted person-level analysis revealed DMSS sensitivity = 93.8% (95%CI = 91.1, 95.8), specificity = 87.0% (79.0, 92.3), PPV = 85.6% (77.2, 91.3) and NPV = 94.5% (91.7, 96.4). Report of anthrax vaccination within a +/-7 days window in both medical chart and DMSS electronic data had a sensitivity of 88.3% (85.4, 90.7) and a PPV of 86.6% (84.9, 88.2) in the vaccine dose-level analysis. CONCLUSIONS: These results support that anthrax vaccination data captured by the DMSS are adequate for post-marketing surveillance investigations in the U.S. military and are of comparable quality to data captured by other vaccine safety databases.     

Factors influencing laboratory workers' decisions to accept or decline anthrax vaccine adsorbed (AVA): results of a decision-making study in CDC's anthrax vaccination program

BACKGROUND: Laboratory technicians, laboratory supervisors, decontamination/remediation workers, and environmental investigators are at increased risk for repeated occupational exposure to Bacillus anthracis. In 2002, the Advisory Committee on Immunization Practices (ACIP) recommended pre-exposure vaccination for these occupational groups. OBJECTIVES: To determine (1) the factors that influenced an individual's decision to either accept or decline Anthrax Vaccine Adsorbed (AVA), and (2) if laboratory workers' concern about AVA safety was related to their information needs and trust in the information provided. METHODS: We conducted a decision-making survey of 404 participants at 44 Laboratory Response Network laboratories located throughout the United States. All participants were enrolled between October 2002 and December 2004, and all were eligible to receive AVA according to the 2002 ACIP recommendations. Chi-square tests and multivariate logistic regression were used in the analyses. RESULTS: The response rate of eligible individuals at participating laboratories was 94% (404/430). Sixty-six percent of respondents accepted and 34% declined AVA. Laboratory workers who declined AVA were more likely to rate their risk of exposure to inhalation anthrax as low (OR = 6.9; 95%CI 1.7, 28.3), report being very concerned (OR = 4.1; 95%CI 1.8, 9.3) or concerned (OR = 2.0; 95%CI 1.3, 3.1) about the safety of the vaccine, report that they did not trust the information provided in the Vaccine Information Statement (VIS) (OR = 2.3; 95%CI 1.1, 4.5), and to be enrolled in the study during 2002 (OR = 24.7; 95%CI 6.4, 95.3) or 2003 (OR = 5.0; 95%CI 2.5, 9.8), the first 2 years of the study. Furthermore, we found a significant association between a participant's level of concern about the safety of AVA and their perception that they received enough information and/or trusted the information in the VIS. CONCLUSIONS: Low perceived necessity, concern about the safety of the vaccine, and a lack of trust in the VIS were associated with the decision of laboratory workers to decline AVA. Results of this decision-making study may be used to try to improve acceptance rates of AVA among persons considered at high risk, and may inform educational efforts for other adult vaccines.     

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.     

基于美国FDA不良事件报告系统数据库的玛巴洛沙韦不良事件风险信号挖掘CSCD

Objective To mine the risk signals of baloxavir marboxil-related adverse events (AEs) and provide reference for rational use in clinical practice. Methods The report odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to mine the risk signals of baloxavir marboxil-related AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the 1st quarter of 2018 to the 4th quarter of 2022. The AE with reports ≥3 and 95% confidence interval (CI) lower limit of ROR or PRR>1 was defined as a risk signal. AEs were classified according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) 25.1 for statistical analysis. Results A total of 1 102 AE reports were retrieved, involving 1 102 patients, and 498 were serious AE. A total of 45 AE risk signals were obtained by ROR and PRR methods. The top 10 PTs in signal intensity were febrile seizures, ischemic colitis, bacterial pneumonitis, anaphylaxis, hemorrhagic cystitis, erythema multiforme, melena, anaphylactic shock, disseminated intravascular coagulation, and anaphylactic reaction. Of them, 26 PTs were not recorded in the labels, in which the top 10 PTs were febrile seizures, ischemic colitis, bacterial pneumonia, hemorrhagic cystitis, disseminated intravascular coagulation, altered mental status, fever, rhabdomyolysis, cyanosis, and facial paralysis. The top 5 SOCs that involved more PTs were nervous system disorders, gastrointestinal disorders, respiratory system diseases, psychiatric disorders, and blood and lymphatic system disorders. Among the 498 serious AEs, a total of 5 risk signals were mined, including infectious pneumonia, diarrhea, rhabdomyolysis, allergic reactions, and abnormal behavior. Conclusion The attention should be paid to AEs not mentioned in the drug label in clinical application of baloxavir marboxil, such as febrile seizures, bacterial pneumonia, ischemic colitis, and hemorrhagic cystitis. © 2023 Chinese Medical Association. All rights reserved.     

Multiple sclerosis as an adverse drug reaction: clues from the FDA Adverse Event Reporting System

Background: Possible relationship between drug exposure and multiple sclerosis (MS) development is insufficiently investigated, and further challenged by the incomplete understanding of MS etiopathogenesis. The study aims to investigate whether drug exposure could contribute to MS, by analyzing worldwide spontaneous reporting archives of adverse drug reaction (ADRs).

Research design and methods: We retrieved information from the US Food and Drug Administration Adverse Event Reporting System (FAERS) over a 13-year period. Reporting odds ratio (ROR) for MS was calculated for each single substance. Disproportionality signals were considered when at least 10 cases were retrieved with a lower limit of the 95% confidence interval (CI) >1.

Results: After a customized data-mining process, 3,226 reports of MS were retrieved. ‘Antineoplastic and immunomodulating drugs’ (33% of total reports) were the most frequently reported, with 10 disproportionality signals, including etanercept (445 cases; ROR: 2.48; 95% Cl: 2.24–2.74), adalimumab (329; 2.05; 1.83–2.30), and infliximab (119; 2.25; 1.87–2.70). We also observed signals for drugs acting on hormone balance, bone density, and central nervous system.

Conclusion: Our findings suggest that immunomodulatory drugs increase the risk of MS and point out that some other drug classes should be further investigated for this risk.     

美国甲型H1N1流感疫苗安全性监测探析与思考

2009年甲型H1N1流感病毒暴发流行以来,各国均开展了甲型H1N1流感疫苗免疫接种工作.本文通过探讨美国政府针对免疫接种后疫苗安全性监测所采取的措施,比较我国与美国在疫苗不良事件监测工作中存在的差距,为我国药物警戒工作的深入发展提供借鉴.     

Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)

Background: To examine how closely reporting rates in the FDA Adverse Event Reporting System (FAERS) reflect expected rates of known adverse drug events (ADEs).

Methods: We selected three groups of drugs to reflect hypothesized variation in sensitivity to reporting, including statins, biologics, and narrow therapeutics index drugs (NTI). The numbers of ADEs in FAERS were divided by utilization estimates from ambulatory health care data (NAMCS/NHAMCS) to calculate a reported proportion. One sample z-test for proportions compared the proportion of ADEs reported to an expected ADE proportion derived from drug labels, reference databases, and peer-reviewed papers.

Results: The majority of drug-ADE pairs showed significant under-reporting. For example, roughly 0.01% to 44% of statin events were reported (z-test p < 0.0001). Biological (0.002% to >100%) and NTI (20% to >100%) drugs had relatively higher reporting rates. Roughly 20% to 33% of the minimum number of expected serious events were reported with biologics and NTI drugs.

Conclusions: This study supports previous evidence of under-reporting of ADEs in spontaneous reporting data. But, under-reporting varies considerably by the type of drug and the type of ADEs, and this variability in under-reporting should be considered when interpreting safety signals.     

A review of medication incidents reported to the National Reporting and Learning System in England and Wales over 6 years (2005-2010)

A review of all medication incidents reported to the National Reporting and Learning System (NRLS) in England in Wales between 1 January 2005 and 31 December 2010 was undertaken. The 526,186 medication incident reports represented 9.68% of all patient safety incidents. Medication incidents from acute general hospitals (394,951) represented 75% of reports. There were relatively smaller numbers of medication incident reports (44,952) from primary care, representing 8.5% of the total. Of 86,821 (16%) medication incidents reporting actual patient harm, 822 (0.9%) resulted in death or severe harm. The incidents involving medicine administration (263,228; 50%) and prescribing (97,097; 18%) were the process steps with the largest number of reports. Omitted and delayed medicine (82,028; 16%) and wrong dose (80,170; 15%) represented the largest error categories. Thirteen medicines or therapeutic groups accounted for 377 (46%) of the incidents with outcomes of death or severe harm. The National Patient Safety Agency (NPSA) has issued guidance to help minimize incidents with many of these medicines. Many recent incidents could have been prevented if the NPSA guidance had been better implemented. It is recommended that healthcare organizations in all sectors establish an effective infrastructure to oversee and promote safe medication practice, including an annual medication safety report. In the future, preventable harms from medication incidents can be further minimized by; the continued use of the NRLS to identify and prioritize important actions to improve medication safety, a central organization continuing to issue medication safety guidance to the service and better methods to ensure that the National Health Service has implemented this guidance.