Abstract
Cluster randomized trials (cRCT) to assess vaccine effectiveness incorporate indirect effects of vaccination, helping to inform vaccination policy. To calculate the sample size for a cRCT, an estimate of the intracluster correlation coefficient (ICC) is required. For infectious diseases, shared characteristics and social mixing behaviours may increase susceptibility and exposure, promote transmission and be a source of clustering. We present ICCs from a school-based cRCT assessing the effectiveness of a meningococcal B vaccine (Bexsero, GlaxoSmithKline) on reducing oropharyngeal carriage of Neisseria meningitidis (Nm) in 34,489 adolescents from 237 schools in South Australia in 2017/2018. We also explore the contribution of shared behaviours and characteristics to these ICCs. The ICC for carriage of disease-causing Nm genogroups (primary outcome) pre-vaccination was 0.004 (95% CI: 0.002, 0.007) and for all Nm was 0.007 (95%CI: 0.004, 0.011). Adjustment for social behaviours and personal characteristics reduced the ICC for carriage of disease-causing and all Nm genogroups by 25% (to 0.003) and 43% (to 0.004), respectively. ICCs are also reported for risk factors here, which may be outcomes in future research. Higher ICCs were observed for susceptibility and/or exposure variables related to Nm carriage (having a cold, spending ≥1 night out socializing or kissing ≥1 person in the previous week). In metropolitan areas, nights out socializing was a highly correlated behaviour. By contrast, smoking was a highly correlated behaviour in rural areas. A practical example to inform future cRCT sample size estimates is provided.
Highlights
Controlled trials, randomized at the individual level, have been the mainstay of vaccine efficacy trials, for licensure
As recommended within the ‘CONSORT statement: extension to cluster randomized trials’, here we report the intracluster correlation coefficient (ICC) obtained from a large school-based cluster randomized controlled trial (cRCT) assessing the impact of a meningococcal B (MenB) vaccine (Bexsero, GSK) on pharyngeal carriage of Neisseria meningitidis (Nm) in adolescents in schools in South Australia (SA) in 2017/2018
While it is widely recognized that adjustment for covariates in a model will reduce the estimated ICC [12], this study aimed to explore the impact of fixed characteristics and social behaviours known to increase carriage prevalence and the extent to which they are correlated within clusters, reflecting the degree of social mixing
Summary
Controlled trials, randomized at the individual level, have been the mainstay of vaccine efficacy trials, for licensure. The cluster randomized controlled trial (cRCT) design captures total or overall vaccine effects, offering an advantage in this regard. Individuals within clusters may share similar behaviours, as well as characteristics, that make them more susceptible to infection, but these shared behaviours within the same contact network may predict social mixing (with more or less interpersonal distance), and increased exposure to infection. Intracluster similarities, lead to individual outcomes that are correlated within clusters, rather than independent. Due to this correlation, often quantified as the intracluster correlation coefficient (ICC), the cRCT design requires a larger sample size to estimate treatment effects with the same degree of precision as an individual randomized controlled trial [7]
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