Do coronavirus vaccine challenge trials have a distinctive generalisability problem?

Area of Science:

• Vaccinology
• Clinical Trial Design
• Infectious Disease Epidemiology

Background:

• Conventional field trials for COVID-19 vaccines have shown success.
• Human challenge trials (HCTs) offer a new avenue for vaccine research.
• Concerns exist regarding the generalizability of HCT data to vulnerable populations.

Purpose of the Study:

• To address critiques of COVID-19 HCTs concerning population generalizability.
• To explore how HCTs can provide insights applicable to high-risk groups.
• To examine the role of HCTs in expediting vaccine protection for all populations.

Main Methods:

• The study critically evaluates the generalizability limitations inherent in both HCTs and field trials.
• It proposes a conceptual framework for how HCTs can inform vaccine strategies for high-risk individuals.
• Analysis focuses on the potential of HCTs to expedite protection, even without direct challenge of high-risk participants.

Main Results:

• Both HCTs and field trials have inherent limitations in generalizability.
• HCTs can expedite the process of determining vaccine efficacy, including for high-risk groups.
• HCTs facilitate obtaining generalizable results applicable to populations excluded for safety reasons.

Conclusions:

• HCTs are a valuable tool for vaccine research, complementing traditional field trials.
• Strategies exist to leverage HCT data to infer protection for high-risk populations.
• HCTs can accelerate the availability of effective vaccines for diverse demographic groups, including the elderly and those with comorbidities.