Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jul 26;15(1):138.
doi: 10.1186/s12916-017-0911-8.

The public health value of vaccines beyond efficacy: methods, measures and outcomes

A Wilder-Smith  1   2   3 , I Longini  4 , P L Zuber  5 , T Bärnighausen  6 , W J Edmunds  7 , N Dean  4 , V Masserey Spicher  8 , M R Benissa  9 , B D Gessner  10
Affiliations

The public health value of vaccines beyond efficacy: methods, measures and outcomes

A Wilder-Smith et al. BMC Med. .

Abstract

Background: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages.

Discussion: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination.

Conclusions: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions.

Keywords: Cluster randomised controlled trial; Dynamic modelling; Effectiveness; Overall effectiveness; Post-licensure; Pre-licensure; Public health impact; Quasi-experiments; Vaccine efficacy; Vaccine-preventable disease incidence.

PubMed Disclaimer

Conflict of interest statement

Competing interests

BDG works with AMP, which currently receives grant-specific support from GSK, Merck, Pfizer and Sanofi Pasteur, and has received support from Crucell, Hilleman Laboratories and Novartis during the past 3 years; in addition to his role with AMP, BDG currently works with Pfizer. All other authors have no conflicts to declare. PLZ is an employee of and IL is a consultant to the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the World Health Organization.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Value chain of vaccines
Fig. 2
Fig. 2
Types of vaccine effectiveness, as developed by Halloran et al. [34]. Cluster 1 has a fraction of the population vaccinated, while cluster 2 has no person vaccinated. The u and v indices designate vaccinated and unvaccinated people, respectively. Direct effectiveness compares the attack rate (AR) (or some other rate measure, e.g. incidence) of vaccinated to unvaccinated people within a cluster, as in cluster 1. Indirect effectiveness compares the AR in unvaccinated people in the partially vaccinated cluster 1 to the AR in an unvaccinated cluster 2. Total effectiveness compares the AR of vaccinated people in cluster 1 to the AR in cluster 2. Finally, overall effectiveness compares the AR among all people in cluster 1 (i.e. vaccinated and unvaccinated) to the AR among all people in cluster 2
See this image and copyright information in PMC

References

    1. Council for International Organizations of Medical Sciences . CIOMS Guide to Active Vaccine Safety Surveillance: Report of CIOMS Working Group on Vaccine Safety. Geneva: CIOMS; 2017.
    1. Andrews N. Epidemiological designs for vaccine safety assessment: methods and pitfalls. Biologicals. 2012;40(5):389–92. doi: 10.1016/j.biologicals.2011.08.010. - DOI - PubMed
    1. Saadatian-Elahi M, Horstick O, Breiman RF, Gessner BD, Gubler DJ, Louis J, Parashar UD, Tapia R, Picot V, Zinsou JA, et al. Beyond efficacy: the full public health impact of vaccines. Vaccine. 2016;34(9):1139–47. doi: 10.1016/j.vaccine.2016.01.021. - DOI - PMC - PubMed
    1. Clemens J, Brenner R, Rao M, Tafari N, Lowe C. Evaluating new vaccines for developing countries. Efficacy or effectiveness? JAMA. 1996;275(5):390–7. doi: 10.1001/jama.1996.03530290060038. - DOI - PubMed
    1. Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, Carroll MW, Doumbia M, Draguez B, Duraffour S, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015;386(9996):857–66. doi: 10.1016/S0140-6736(15)61117-5. - DOI - PubMed