BACKGROUND Vaccine hesitancy has increased in recent decades internationally, which set up a critical barrier to rapid deployment of novel vaccines against infection with COVID-19. OBJECTIVE This study used a quasi-experimental design to evaluate the cost-effectiveness of a quasi-experimental social media intervention to reduce COVID-19 vaccine hesitancy implemented in Nigeria in 2022. METHODS The intervention targeted healthcare providers and adults from the general population who were users of a specific social media platform. We used published estimates from a quasi-experimental evaluation of the campaign’s effectiveness compared to the status quo assigned across 6 intervention states and 31 comparison states over a 10-month period. We estimated the cost-effectiveness of the campaign in terms of cost (2022) per person vaccinated using a decision-tree analysis and probabilistic sensitivity analysis. RESULTS The social media campaign resulted in 58. 3 million impressions and 1. 87 million people reached for a total societal cost of 1. 15 million, or 0. 613 per person reached. The campaign led to a 1. 57 (95% Uncertainty Interval (UI): 0. 337, 2. 87) percentage point increase in the proportion of those vaccinated against COVID-19 among those reached by the social media campaign compared to those in comparison states. This resulted in an incremental cost-effectiveness ratio of 54. 70 (95% UI: 20. 90, 163) per person vaccinated. CONCLUSIONS A social media-based campaign to address COVID-19 vaccine hesitancy in six states in Nigeria resulted in an increase in vaccination rates. The cost-effectiveness of the campaign compared to no campaign is comparable to other campaigns promoting COVID-19 vaccine uptake and is 1-8% of the estimated cost per life year saved by vaccination against COVID-19 in low and middle-income countries. Investing in social media campaigns would likely be a cost-effective approach to increase vaccine uptake and save lives. CLINICALTRIAL Pan African Clinical Trial Registry: PACTR202310811597445
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