Test-Negative Designs With Multiple Testing Sources

Area of Science:

• Epidemiology
• Vaccinology
• Biostatistics

Background:

• Test-negative designs (TND) are widely used to evaluate infectious disease interventions, including vaccines for influenza and COVID-19.
• Traditional TND relies on symptomatic individuals, but modern applications include asymptomatic cases, potentially introducing bias.
• The 'multiple reasons for testing' problem arises when individuals are tested for various reasons beyond symptoms, complicating efficacy assessments.

Purpose of the Study:

• To address bias in test-negative designs caused by aggregating symptomatic and asymptomatic test results.
• To propose and examine a method for estimating vaccine efficacy in the context of multiple testing sources, using an Ebola vaccine trial as a case study.
• To assess whether vaccine efficacy is consistent across different sources of test results (symptomatic vs. contact tracing).

Main Methods:

• Utilized a modified test-negative design framework inspired by an Ebola viral disease (EVD) vaccine trial.
• Incorporated data from both symptomatic individuals presenting for care and asymptomatic close contacts of confirmed cases.
• Developed an approach to estimate common vaccine efficacy and assess its consistency across different testing pathways.

Main Results:

• The study examines a novel approach to estimate vaccine efficacy from combined symptomatic and asymptomatic testing data.
• It provides a method to evaluate if the intervention's effectiveness differs between individuals tested due to symptoms versus those tested via contact tracing.
• The proposed methodology is crucial for accurate efficacy assessment in complex trial designs.

Conclusions:

• The proposed method offers a way to mitigate bias in test-negative designs arising from multiple reasons for testing.
• This approach is vital for accurately evaluating vaccine efficacy, particularly in scenarios involving both symptomatic and asymptomatic individuals.
• The methodology remains relevant for future infectious disease vaccine trials, especially if the EVD trial is recommenced.