Real world evidence for public health decision-making on vaccination policies: perspectives from an expert roundtable

ABSTRACT

Introduction

Influenza causes significant morbidity and mortality, but influenza vaccine uptake remains below most countries’ targets. Vaccine policy recommendations vary, as do procedures for reviewing and appraising the evidence.

Areas Covered

During a series of roundtable discussions, we reviewed procedures and methodologies used by health ministries in four European countries to inform vaccine recommendations. We review the type of evidence currently recommended by each health ministry and the range of approaches toward considering randomized controlled trials (RCTs) and real-world evidence (RWE) studies when setting influenza vaccine recommendations.

Expert Opinion

Influenza vaccine recommendations should be based on data from both RCTs and RWE studies of efficacy, effectiveness, and safety. Such data should be considered alongside health-economic, cost-effectiveness, and budgetary factors. Although RCT data are more robust and less prone to bias, well-designed RWE studies permit timely evaluation of vaccine benefits, effectiveness comparisons over multiple seasons in large populations, and detection of rare adverse events, under real-world conditions. Given the variability of vaccine effectiveness due to influenza virus mutations and increasing diversification of influenza vaccines, we argue that consideration of both RWE and RCT evidence is the best approach to more nuanced and timely updates of influenza vaccine recommendations.

KEYWORDS:

• Influenza
• influenza vaccination
• vaccine effectiveness
• vaccination recommendations
• evidence base
• evaluation methodology
• public health

Article highlights

• European health ministries develop national influenza vaccine recommendations based on evidence from randomized controlled trials (RCTs), real-world evidence (RWE) studies, and analyses of disease burden and economic impact

• The degree to which any given type of evidence is used varies by country, with some countries placing greater emphasis on RCTs while others rely more on RWE studies

• Although RCT data are more robust and less prone to bias, well-designed RWE studies permit timely evaluation of vaccine benefits, effectiveness comparisons over multiple seasons in large populations, and detection of rare adverse events, under real-world conditions

• Consideration of both RWE and RCTs evidence would permit health ministries to develop more nuanced and timely updates of influenza vaccine recommendations

Abbreviations

ACIP, US Advisory Committee on Immunization Practices; aQIV, adjuvanted quadrivalent influenza vaccine; DHSC, Department of Health and Social Care; DRIVE, Development of Robust and Innovative Vaccine Effectiveness; ECDC, European Center for Disease Prevention and Control; EMA, European Medicines Agency; EtD, Evidence to Decision; EtR, Evidence to Recommendations; EU, European Union; GISRS, Global Influenza Surveillance and Response System; GRACE, Good Research for Comparative Effectiveness; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HTA, Health Technology Assessment; I-MOVE, Influenza – Monitoring Vaccine Effectiveness in Europe; JCVI, Joint Committee on Vaccination and Immunization; LAIV, live attenuated influenza vaccine; NHS, National Health Service; NITAG, national immunization technical advisory group; NRSI, nonrandomized studies of interventions; QIV-HD, high-dose quadrivalent influenza vaccine; QIVc, cell-based quadrivalent influenza vaccine; QIVr, recombinant quadrivalent influenza vaccine; RCT, randomized controlled trial; RKI, Robert Koch Institute; RoB 2, Revised Tool for Assessing Risk of Bias; ROBINS-I, Risk of Bias in Non-randomized Studies of Interventions; RSV, respiratory syncytial virus; RWE, real-world evidence; SAGE, Strategic Advisory Group of Experts on Immunization; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SIKO, State Committee on Vaccination; STIKO, Standing Committee on Vaccination; VE, vaccine effectiveness VEBIS, Vaccine Effectiveness, Burden and Impact Studies; WHO, World Health Organization.

Declaration of interests

C de Waure reports receiving honoraria from CSL Seqirus and MSD for research and advisory activities. BC Gärtner reports receiving honoraria for lectures and advisory boards from CSL Seqirus, Sanofi, BionTech, Moderna, and Viatris. PLL reports honoraria from CLS Seqirus, GSK, Moderna, MSD, Novavax, Pfizer, and Sanofi as advisor or speaker in conference symposia and educational activities. J Puig-Barberà reports honoraria from CSL Seqirus, Novavax, Sanofi and HIPRA as advisor and speaker in educational activities. JS Nguyen-Van-Tam was seconded to the Department of Health and Social Care, England (DHSC) from October 2017 – March 2022. After ending this role, he reports consulting fees from CSL Seqirus Ltd, and lecture fees from AstraZeneca and Sanofi Pasteur, all of whom manufacture influenza vaccines. From May 2023 onwards he reports consulting fees from Moderna Therapeutics Inc., which is developing future influenza vaccines. The views expressed in this article are not necessarily those of DHSC or its agencies, nor of the companies mentioned above. 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 material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has disclosed that they receive grant funding from Sanofi. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

All authors participated in the discussion and the development of this manuscript and reviewed and approved the final manuscript.

Data availability statement

Data are derived from public domain resources and are referenced in the manuscript.

Acknowledgments

The authors would like to thank medical consultant C. Gordon Beck for medical writing assistance in the preparation of this paper.

Additional information

Funding

CSL Seqirus funded all costs associated with the development and publishing of the present manuscript.