Evaluation of COVID-19 vaccine products and schedules

Research Question How do different COVID-19 vaccine schedules and products influence safety and effectiveness of vaccination? Background Booster vaccination continues to be an important intervention in the fight against COVID-19. However, evidence on the impact of booster timing and spacing (or "schedules") on vaccine effectiveness is limited. As schedules experienced in national COVID-19 booster programmes are much more diverse than those directed in trials, there is an opportunity to use large-scale routinely collected health data to evaluate the impact of different schedules on important outcomes. Aims and Objectives To comprehensively describe vaccine schedules received in the English population since the start of the pandemic, including products and intervals, and in important population subgroups. To understand which characteristics influence vaccine schedules, including sub-optimal or delayed boosters, in specific population subgroups over time. To evaluate the long-term safety and effectiveness of different vaccination intervals and products against severe COVID-19 related outcomes. Methods Data: We will use the OpenSAFELY platform, providing secure access to large-scale linked primary care records across England. WP1: We will describe, through regular reports, the use of vaccine products and schedules, including combinations and timings, received across England over successive vaccination campaigns and in important population subgroups. WP2: We will identify and describe characteristics that influence vaccination, including time to vaccination, in population subgroups over time. This will inform more rigorous eligibility and confounder selection in subsequent causal analyses in WP3 and also feed directly into causal analyses via propensity or inverse probability of treatment weighting methods. WP3: We will use the Clone-Censor-Weight approach to evaluate the safety and effectiveness of competing vaccination strategies including timing, spacing, and product types, covering previous and upcoming COVID-19 booster programmes in England. We will also produce a "how to" tutorial describing how to use the Clone-Censor-Weight to conduct observational analyses that are vulnerable to immortal time bias due to patients experiencing treatment patterns consistent with multiple competing treatment strategies of interest. Patient and Public Involvement: The design and delivery of the research will be informed by a public advisory group who will contribute frequently throughout the project. Timelines for delivery Reports on national vaccine schedules and products will be updated regularly throughout the project. Studies will be planned in advance of specific booster programmes to ensure that they are conducted and disseminated as soon as possible after sufficient follow-up has elapsed. Studies will be updated to report on longer follow-up. Anticipated impact and dissemination All research outputs (papers, protocols, reports, summary data, research code) will be openly accessible for researchers and the public. Research will be submitted to scientific journals for peer review and publication, and presented at epidemiology conferences. We will also discuss findings directly with relevant research and policy groups - via conferences, national vaccine working groups, and advisory committees - to maximise impact on future COVID-19 vaccination programmes in the UK and elsewhere. We will also openly publish research code and summary data to help other researchers reuse our methods and findings in new contexts.