Proposed study design for estimating COVID-19 vaccine effectiveness in post-pandemic Taiwan

Area of Science:

• Epidemiology
• Public Health
• Vaccinology

Background:

• Post-licensure observational studies are crucial for vaccine effectiveness (VE) assessment when randomized controlled trials are infeasible.
• Existing studies often lack clarity on the specific types of vaccine effects estimated.
• The test-negative design (TND), commonly used for influenza and SARS-CoV-2, has limitations and requires specific surveillance platforms.

Purpose of the Study:

• To delineate the types of vaccine effects captured in current observational VE studies.
• To propose a scientifically rigorous and operationally feasible study design for estimating COVID-19 VE against severe outcomes in the post-pandemic era.
• To offer an alternative to the TND for direct VE assessment, particularly in the absence of sentinel surveillance.

Main Methods:

• A comprehensive review of methodological issues in VE studies, including vaccine effect, study design, outcomes, exposures, and covariates.
• Consideration of Taiwan's post-pandemic context and healthcare system.
• Proposal of a refined population-based retrospective cohort design utilizing integrated national databases.

Main Results:

• The proposed design enables the estimation of direct VE against severe COVID-19 outcomes.
• It incorporates validated markers of health-seeking behavior, healthcare access, and underlying health conditions.
• Advanced statistical models are integrated for robust analysis.

Conclusions:

• The refined population-based retrospective cohort design offers a scientifically valid and feasible alternative to the TND for COVID-19 VE assessment.
• This design is adaptable for evaluating other respiratory pathogen vaccines, such as the seasonal influenza vaccine.
• The methodology is suitable for countries with integrated national health databases and similar healthcare settings.