Adopting the estimand framework in prophylactic vaccine trials

Area of Science:

• Clinical trial methodology
• Vaccinology
• Biostatistics

Background:

• The ICH E9(R1) estimand framework is established for therapeutic trials.
• Preventive vaccine trials have unique characteristics, notably the focus on biological effect.
• Limited guidance exists for applying the estimand framework to vaccine trials.

Purpose of the Study:

• To comprehensively review the application of the estimand framework in preventive vaccine trials.
• To address challenges in defining and handling intercurrent events specific to vaccine studies.
• To provide practical guidance for protocol development and statistical analysis plans.

Main Methods:

• Review of the ICH E9(R1) estimand framework.
• Application of the framework to vaccine trial scenarios.
• Discussion of intercurrent events: noncompliance, infection, death, prohibited products.
• Considerations for strategy selection to address scientific questions.

Main Results:

• The framework can be adapted for vaccine trials evaluating clinical and immunogenicity endpoints.
• Specific strategies for handling intercurrent events are discussed.
• Guidance is provided on summarizing estimands and data handling.

Conclusions:

• The estimand framework offers a robust approach for vaccine trial design and analysis.
• Careful consideration of intercurrent events is crucial for interpretable vaccine trial results.
• This work provides a foundation for consistent application of the estimand framework in vaccine research.