Assessing vaccine efficacy in influenza clinical trials: challenges and difficulties

Abstract

The efficacy assessment of an influenza vaccine often requires conducting large and expensive clinical trials. Specificities of influenza increase the complexity of the study designs, of the subsequent statistical analysis and of the interpretation of the results. They include low attack rates, seasonality, multiplicity and frequent mutations of flu viruses as well as heterogeneity of virus circulation, varying annual vaccine composition and so on. The authors discuss how those factors may impact the design, the conduct and the analysis of an efficacy trial and explain why it may fail whatever the true vaccine efficacy. The authors then argue that extending the length to several consecutive seasons is an alternative to the frequently used 1-year design and propose refinements of the statistical models.

Keywords::

• seasonal influenza
• specificities
• statistical methodology
• study design
• vaccine efficacy

Acknowledgements

W Dewe and A Benoit drafted the manuscript; all authors were involved in revising it critically for important intellectual content, and final approval of the manuscript. The authors would like to express their gratitude to some of their colleagues who kindly reviewed the manuscript and provided valuable comments. In particular, we thank Christelle Durand, Fabian Tibaldi, François Beckers, Géraldine Drevon, Lidia Oostvogels, Marc Fourneau and Ping Li (GlaxoSmithKline Vaccines).

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official position of GlaxoSmithKline Vaccines.

Financial & competing interests disclosure

This work was partially supported by a grant from GlaxoSmithKline Vaccines to Université Catholique de Louvain. Support from the IAP Research Network P7/06 of the Belgian State (Belgian Science Policy) is gratefully acknowledged. C Legrand and A Benoit acknowledge further financial support from the contract Projet d’Actions de Recherche Concertées 11/16-039 of the Communautéfrançais de Belgique granted by the Académie Universitaire Louvain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.