ABSTRACT
OBJECTIVE: Despite the public health value of vaccines, vaccination uptake rates are stagnating. Expected adverse events following immunization are a major source of concern and play a role in the emergence of vaccine hesitancy. Since nocebo mechanisms are involved in the perception of adverse reactions, positive side-effect communication is warranted. The aim of the present study was to compile a comprehensive communication strategy that minimizes expectations of nocebo effects while respecting the informed consent procedure. METHOD: In a randomized 2 × 2 between-subject design, 652 participants received information about COVID-19 or influenza vaccination using either standard side-effect messaging or messaging enriched with proven elements of expectation-optimizing framing. A physician presented information online via video. Moderation analyses were conducted to examine effects among particular subpopulations. Expected adverse event ratings following an imagined immunization, cost-benefit ratios of the vaccination, and future vaccination intentions were assessed. RESULTS: Information content ratings were equally high in each group. Positive framing significantly decreased adverse event expectations in the COVID-19 information group and raised the cost-benefit ratio in the influenza condition, indicating higher benefits than cost expectations. Moderation analysis revealed that the framed side-effect communication lowered the expected COVID-19 vaccination uptake willingness in individuals with strong anti-vaccination attitudes. CONCLUSIONS: Facing the ongoing coronavirus mass vaccinations, positive information frames have a small but significant impact on vaccination concerns while upholding informed consent. Although intervention trials are still pending, this approach could help decrease vaccine hesitancy by reducing fearful expectations. However, it seems that it should not be used without considering vaccination attitudes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
ABSTRACT
Importance: Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective: To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources: For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection: Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis: Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures: The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results: Twelve articles with AE reports for 45â¯380 participants (22â¯578 placebo recipients and 22â¯802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, -0.47; 95% CI, -0.54 to -0.40; P < .001; standardized mean difference, -0.26; 95% CI, -0.30 to -0.22) and large after the second dose (OR, -1.36; 95% CI, -1.86 to -0.86; P < .001; standardized mean difference, -0.75; 95% CI, -1.03 to -0.47). Conclusions and Relevance: In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms.