新型冠状病毒疫苗随机试验中活性组和安慰剂组的不良事件：一项系统评价。
Adverse events of active and placebo groups in SARS-CoV-2 vaccine randomized trials: A systematic review.
作者信息
Amanzio Martina, Mitsikostas Dimos D, Giovannelli Fabio, Bartoli Massimo, Cipriani Giuseppina Elena, Brown Walter A
机构信息
Department of Psychology, University of Turin, Via Verdi 10, 10124 Turin, Italy.
First Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, 72-74 V. Sofia's Avenue, Athens 11528, Hellas, Greece.
出版信息
Lancet Reg Health Eur. 2022 Jan;12:100253. doi: 10.1016/j.lanepe.2021.100253. Epub 2021 Oct 28.
BACKGROUND
For safety assessment in clinical trials, adverse events (AEs) are reported for the drug under evaluation and compared with AEs in the placebo group. Little is known about the nature of the AEs associated with clinical trials of SARS-CoV-2 vaccines and the extent to which these can be traced to nocebo effects, where negative treatment-related expectations favor their occurrence.
METHODS
In our systematic review, we compared the rates of solicited AEs in the active and placebo groups of SARS-CoV-2 vaccines approved by the Western pharmaceutical regulatory agencies.We implemented a search strategy to identify trial-III studies of SARS-CoV-2 vaccines through the PubMed database. We adopted the PRISMA Statement to perform the study selection and the data collection and identified three trial: two mRNA-based (38403 participants) and one adenovirus type (6736 participants).
FINDINGS
Relative risks showed that the occurrence of AEs reported in the vaccine groups was higher compared with the placebo groups. The most frequently AEs in both groups were fatigue, headache, local pain, as injection site reactions, and myalgia. In particular, for first doses in placebo recipients, fatigue was reported in 29% and 27% in BNT162b2 and mRNA-1273 groups, respectively, and in 21% of Ad26.COV2.S participants. Headache was reported in 27% in both mRNA groups and in 24% of Ad26.COV2.S recipients. Myalgia was reported in 10% and 14% in mRNA groups (BNT162b2 and mRNA-1273, respectively) and in 13% of Ad26.COV2.S participants. Local pain was reported in 12% and 17% in mRNA groups (BNT162b2 and mRNA-1273, respectively), and in 17% of Ad26.COV2.S recipients. These AEs are more common in the younger population and in the first dose of placebo recipients of the mRNA vaccines.
INTERPRETATION
Our results are in agreement with the expectancy theory of nocebo effects and suggest that the AEs associated with COVID-19 vaccines may be related to the nocebo effect.
FUNDING
Fondazione CRT - Cassa di Risparmio di Torino, IT (grant number 66346, "GAIA-MENTE" 2019).
背景
在临床试验的安全性评估中，需报告所评估药物的不良事件（AE），并与安慰剂组的不良事件进行比较。对于与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗临床试验相关的不良事件的性质，以及这些不良事件可追溯到安慰剂效应（即与治疗相关的负面期望促使其发生）的程度，人们了解甚少。
方法
在我们的系统评价中，我们比较了西方制药监管机构批准的SARS-CoV-2疫苗的活性组和安慰剂组中主动报告的不良事件发生率。我们实施了一项检索策略，通过PubMed数据库识别SARS-CoV-2疫苗的III期试验研究。我们采用系统评价和Meta分析的首选报告项目（PRISMA）声明进行研究选择和数据收集，并确定了三项试验：两项基于信使核糖核酸（mRNA）的试验（38403名参与者）和一项腺病毒型试验（6736名参与者）。
结果
相对风险显示，与安慰剂组相比，疫苗组报告的不良事件发生率更高。两组中最常见的不良事件是疲劳、头痛、局部疼痛（如注射部位反应）和肌痛。特别是，对于安慰剂接受者的第一剂，BNT162b2组和mRNA-1273组分别有29%和27%的人报告疲劳，Ad26.COV2.S参与者中有21%报告疲劳。两个mRNA组中均有27%的人报告头痛，Ad26.COV2.S接受者中有24%报告头痛。mRNA组（分别为BNT162b2和mRNA-1273）中分别有10%和14%的人报告肌痛，Ad26.COV2.S参与者中有13%报告肌痛。mRNA组（分别为BNT162b2和mRNA-1273）中分别有12%和17%的人报告局部疼痛，Ad26.COV2.S接受者中有17%报告局部疼痛。这些不良事件在年轻人群以及mRNA疫苗安慰剂接受者的第一剂中更为常见。
解读
我们的结果与安慰剂效应的期望理论一致，并表明与2019冠状病毒病（COVID-19）疫苗相关的不良事件可能与安慰剂效应有关。
资金来源
意大利都灵储蓄银行CRT基金会（资助编号66346，“GAIA-MENTE”2019）。
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