Application of estimand framework in ICH E9 (R1) to vaccine trials

ABSTRACT

Over the past decades, the primary interest in vaccine efficacy or immunogenicity evaluation mostly focuses on the biological effect of immunization in complying with the vaccination schedule in a targeted population. The safety questions, which are essential for vaccines as they are generally given to large healthy populations, need to be clearly defined to reflect the risk assessment of interest. ICH E9 (R1) provides a structured framework to clarify the clinical questions and formulate the treatment effect as an estimand. This paper applies the estimand framework to vaccine clinical trials on common clinical questions regarding efficacy, immunogenicity, and safety.

KEYWORDS:

• Vaccine trials
• efficacy
• immunogenicity
• safety
• estimand framework
• intercurrent events

Acknowledgements

We would like to thank the late Guanghan (Frank) Liu for his encouragement and review of this paper before his passing away in January 2022. We would like to thank Jonathan Hartzel, Oliver Bautista, Yu Ding, Ruixue Wang, the Merck ELSTIC estimand working group, and the Merck estimand safety working group who reviewed this paper and provided valuable suggestions that greatly enhanced the research. We are also very grateful to the expert comments from Ping Yang, Jiawei Wei, and journal reviewers that helped improve the paper’s clarity.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.