Statistical considerations for the platform trial in COVID-19 vaccine priming and boosting.

ABSTRACT

The Platform trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, adaptive platform trial designed to generate evidence of the immunogenicity, reactogenicity, and cross-protection of different booster vaccination strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, specific for the Australian context. The PICOBOO trial randomises participants to receive one of three COVID-19 booster vaccine brands (Pfizer, Moderna, Novavax) available for use in Australia, where the vaccine brand subtypes vary over time according to the national vaccine roll out strategy, and employs a Bayesian hierarchical modelling approach to efficiently borrow information across consecutive booster doses, age groups and vaccine brand subtypes. Here, we briefly describe the PICOBOO trial structure and report the statistical considerations for the estimands, statistical models and decision making for trial adaptations. This paper should be read in conjunction with the PICOBOO Core Protocol and PICOBOO Sub-Study Protocol 1 Booster Vaccination. PICOBOO was registered on 10 February 2022 with the Australian and New Zealand Clinical Trials Registry ACTRN12622000238774.