Netherlands Pharmacovigilance Centre Lareb, 's, Hertogenbosch, the Netherlands.
Netherlands Pharmacovigilance Centre Lareb, 's, Hertogenbosch, the Netherlands; Department of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Groningen, the Netherlands.
Vaccine. 2024 Apr 2;42(9):2357-2369. doi: 10.1016/j.vaccine.2024.03.001. Epub 2024 Mar 6.
During the COVID-19 pandemic, EMA set-up a large-scale cohort event monitoring (CEM) system to estimate incidence rates of patient-reported adverse drug reactions (ADRs) of different COVID-19 vaccines across the participating countries. This study aims to give an up to date and in-depth analysis of the frequency of patient-reported ADRs after the 1st, 2nd, and booster vaccination, to identify potential predictors in developing ADRs and to describe time-to-onset (TTO) and time-to-recovery (TTR) of ADRs.
A CEM study was rolled out in a period ranging from February 2021 to February 2023 across multiple European countries; The Netherlands, Belgium, France, the United Kingdom, Italy, Portugal, Romania, Slovakia and Spain. Analysis consisted of a descriptive analyses of frequencies of COVID-19 vaccine-related ADRs for 1st, 2nd and booster vaccination, analysis of potential predictors in developing ADRs with a generalized linear mixed-effects model, analysis of TTO and TTR of ADRs and a sensitivity analysis for loss to follow-up (L2FU).
A total of 29,837 participants completed at least the baseline and the first follow-up questionnaire for 1st and 2nd vaccination and 7,250 participants for the booster. The percentage of participants who reported at least one ADR is 74.32% (95%CI 73.82-74.81). Solicited ADRs, including injection site reactions, are very common across vaccination moments. Potential predictors for these reactions are the brand of vaccine used, the patient's age, sex and prior SARS-CoV-2 infection. The percentage of serious ADRs in the study is low for 1st and 2nd vaccination (0.24%, 95%CI 0.19--0.31) and booster (0.26%, 95%CI 0.15, 0.41). The TTO was 14 h (median) for dose 1 and slightly longer for dose 2 and booster dose. TTR is generally also within a few days. The effect of L2FU on estimations of frequency is limited.
Despite some limitations due to study design and study-roll out, CEM studies can allow prompt and almost real-time observations of the safety of medications directly from a patient-centered perspective, which can play a crucial role for regulatory bodies during an emergency setting such as the COVID-19 pandemic.
在 COVID-19 大流行期间，EMA 建立了一个大规模的队列事件监测（CEM）系统，以估计参与国家不同 COVID-19 疫苗的患者报告不良药物反应（ADR）的发生率。本研究旨在对第 1 剂、第 2 剂和加强剂接种后患者报告的 ADR 频率进行最新和深入的分析，确定发生 ADR 的潜在预测因素，并描述 ADR 的发病时间（TTO）和恢复时间（TTR）。
在 2021 年 2 月至 2023 年 2 月期间，在多个欧洲国家（荷兰、比利时、法国、英国、意大利、葡萄牙、罗马尼亚、斯洛伐克和西班牙）开展了一项 CEM 研究。分析包括对第 1 剂、第 2 剂和加强剂接种的 COVID-19 疫苗相关 ADR 频率进行描述性分析，使用广义线性混合效应模型分析发生 ADR 的潜在预测因素，分析 ADR 的 TTO 和 TTR，并对随访丢失（L2FU）进行敏感性分析。
共有 29837 名参与者至少完成了第 1 剂和第 2 剂接种的基线和第 1 次随访问卷，7250 名参与者完成了加强剂接种的问卷。报告至少一种 ADR 的参与者比例为 74.32%（95%CI 73.82-74.81）。在各接种时刻，包括注射部位反应在内的疫苗接种后即刻不良反应十分常见。这些反应的潜在预测因素是使用的疫苗品牌、患者年龄、性别和既往 SARS-CoV-2 感染。第 1 剂和第 2 剂接种（0.24%，95%CI 0.19%-0.31%）和加强剂接种（0.26%，95%CI 0.15%-0.41%）的严重 ADR 比例较低。第 1 剂和第 2 剂接种的 TTO 为 14 小时（中位数），加强剂接种的 TTO 稍长。TTR 通常也在几天内。随访丢失对频率估计的影响有限。
尽管由于研究设计和研究开展存在一些局限性，但 CEM 研究可以直接从以患者为中心的角度及时、近乎实时地观察药物的安全性，这在 COVID-19 大流行等紧急情况下对监管机构至关重要。
