Grading of recommendations, assessment, development, and evaluation (GRADE): Moderna COVID-19 vaccine for children aged 6­11 years

ABSTRACT

A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) review of the evidence for benefits and harms for Moderna coronavirus disease 2019 (COVID-19) vaccine for children aged 6­11 years was presented to the Advisory Committee for Immunization Practices (ACIP) on June 23, 2022. GRADE evidence type indicates the certainty in estimates from the available body of evidence. Evidence certainty ranges from type 1 (high certainty) to type 4 (very low certainty) [1]. The policy question was, "Should vaccination with Moderna COVID-19 vaccine (2 doses, 50 µg) be recommended for children 6­11 years of age during an Emergency Use Authorization?" The potential benefits pre-specified by the ACIP COVID-19 Vaccines Work Group included prevention of symptomatic laboratory-confirmed COVID-19 (critical), hospitalization due to COVID-19 (important), multisystem inflammatory syndrome in children (MIS-C) (important), and asymptomatic SARS-CoV-2 infection (important). The two pre-specified harms were serious adverse events (SAEs) (critical) and reactogenicity grade ≥3 (important). A systematic review of evidence on the efficacy and safety of a two-dose regimen of Moderna COVID-19 vaccine among children aged 6­11 years was conducted. The quality of evidence from one Phase II/III randomized controlled trial was assessed using a modified GRADE approach [2]. Symptomatic COVID-19 was less common among the vaccine group compared with the placebo group (RR 0.19; 95% CI 0.05, 0.81; evidence type 2). A non-inferior geometric mean ratio (GMR) for antibodies in the 6­11-year-olds was observed with vaccination compared to the 18­25-year-olds (GMR 1.2, 95% confidence interval [CI] 1.1, 1.4; evidence type 2). A lower risk of asymptomatic SARS-CoV-2 infection also seen in the vaccine group compared with the placebo group (Relative Risk [RR] 0.29; 95% CI 0.12, 0.71; evidence type 3). The available data indicated that SAEs were balanced between the vaccine and placebo arms, but certainty in the estimate was very low (RR 0.99; 95% CI 0.20, 4.91; evidence type 4); none of these SAEs were assessed by the Food and Drug Administration (FDA) as related to study intervention. Reactogenicity grade ≥3 was associated with vaccination (RR 5.2; 95% CI 3.6, 7.3; evidence type 1). About 17% of vaccine recipients and 3% of placebo recipients reported any grade ≥3 local or systemic reactions following either dose 1 or dose 2.