Clinical and Epidemiology Research and Development, GlaxoSmithKline Vaccines B.V., Amsterdam, The Netherlands.
Vaccinology and Immunology Research Trials Unit, Women's and Children's Health Network, Adelaide, South Australia, Australia.
PLoS One. 2021 Oct 14;16(10):e0254330. doi: 10.1371/journal.pone.0254330. eCollection 2021.
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.
群组随机对照试验（cRCT）评估疫苗有效性时纳入了疫苗的间接效果，有助于为疫苗接种政策提供信息。为了计算 cRCT 的样本量，需要估计组内相关系数（ICC）。对于传染病，共同特征和社交混合行为可能会增加易感性和暴露风险，促进传播，并成为聚类的来源。我们报告了 2017/2018 年在南澳大利亚的 237 所学校的 34489 名青少年中进行的一项基于学校的 cRCT 的 ICC，该试验评估了脑膜炎 B 疫苗（Bexsero，葛兰素史克）在降低脑膜炎奈瑟菌（Nm）口咽部携带率方面的有效性。我们还探讨了共同行为和特征对这些 ICC 的贡献。接种前导致疾病的 Nm 基因型（主要结局）的携带 ICC 为 0.004（95%CI：0.002，0.007），而所有 Nm 的携带 ICC 为 0.007（95%CI：0.004，0.011）。调整社会行为和个人特征后，导致疾病的 Nm 基因型和所有 Nm 基因型组的携带 ICC 分别降低了 25%（至 0.003）和 43%（至 0.004）。这里还报告了风险因素的 ICC，这些因素可能是未来研究的结果。与 Nm 携带相关的易感性和/或暴露变量（感冒、上周至少外出社交 1 晚或亲吻 1 人以上）的 ICC 较高。在大都市区，外出社交是一种高度相关的行为。相比之下，在农村地区，吸烟是一种高度相关的行为。提供了一个实用的示例，用于为未来的 cRCT 样本量估计提供信息。
