Recipient-focused interventions to increase vaccine uptake in high and upper-middle income countries: a systematic review and network meta-analysis.

Background: Vaccination is a highly effective public health tool. However, uptake of many vaccines has declined globally over the past decade, exacerbated by the COVID-19 pandemic, with coverage often falling short of critical thresholds. There is a large evidence-base of vaccine uptake interventions targeting vaccine recipients. Here we aim to synthesise evidence on the comparative effectiveness of these interventions, assess variations by age, and evaluate the impact of the COVID-19 pandemic on intervention effectiveness. Methods: We conducted a systematic review, searching nine databases and grey literature for randomised controlled trials from high and upper-middle income countries, published from 2000 to April 2024. We included interventions targeted at vaccine recipients of any age (or their caregivers) living in the community, aimed at increasing uptake of routine or selective/targeted vaccinations on the UK schedule and categorised them into six intervention categories (access, affordability, education, reminder, education and reminder, and multi-component). Our outcome was number vaccinated. We estimated odds ratios (ORs) using Bayesian random effects network meta-analysis (NMA) combining all direct and indirect evidence on relative intervention effects in a single coherent analysis. Risk of bias was assessed using the Cochrane RoB 2 tool and certainty in the evidence using CINeMA. This review is registered with PROPSERO (CRD42022369139). Findings: We included 268 studies (6,243,118 participants; 39% male, 61% female) with 223 eligible for analysis. Studies not eligible for analysis are narratively reported. Of those eligible for analysis, we assessed 105 studies as low risk of bias, 87 as some concerns, and 31 as high risk. Our NMA produced ORs and 95% credible intervals (CrI) > 1 for all six intervention categories, indicating favourable vaccine uptake compared to control (standard practice, no intervention, or attention placebo), with multicomponent (OR: 2.09, 95% CrI: 1.66-2.63), access (OR: 1.74, 95% CrI: 1.35-2.26), and affordability (OR: 1.87, 95% CrI: 1.47-2.40) interventions appearing most effective followed by education and reminder (OR: 1.47, 95% CrI: 1.29-1.67), reminder (OR: 1.36, 95% CrI: 1.22-1.50), and education (OR: 1.33, 95% CrI: 1.19-1.49). We judged the evidence for all six interventions as moderate certainty. Subgroup analyses exploring the effect of the COVID-19 pandemic suggest that affordability interventions may be less effective post-2020 (OR: 1.35, 95% CrI: 0.94-1.94) than pre-2020 (OR: 2.32, 95% CrI:1.72-3.19), similarly multicomponent interventions appear less effective post-2020 (OR: 1.45, 95% CrI: 1.00-2.10) than pre-2020 (OR: 2.50, 95% CrI: 1.89-3.33) whilst access, education, reminder, and education and reminder intervention effects remained stable. Interpretation: Vaccination programmes in high and upper-middle income countries should prioritise ensuring vaccines are accessible, convenient, and affordable for the recipient. Efforts should be directed towards further investigating and optimising access and affordability interventions. The possible negative impacts of the COVID-19 pandemic on the effectiveness of affordability and multicomponent interventions should be monitored. Funding: NIHR Public Health Research Programme (NIHR135130).