Elsevier

Vaccine

Volume 35, Issue 46, 1 November 2017, Pages 6255-6263
Vaccine

Conference report
Estimating the full public health value of vaccination

https://doi.org/10.1016/j.vaccine.2017.09.048Get rights and content

Abstract

There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually-randomized phase III trials to assess safety and efficacy against etiologically-confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long-term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes.

Following an initial conference at the Fondation Mérieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016.

The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence-base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines.

Introduction

Historically, vaccines have been assessed for inclusion into public immunization programs based on safety and efficacy against severe etiologically-confirmed disease or against serious sequelae [1]. In randomized controlled trials, many factors, including geography, inclusion and exclusion criteria, age, diagnostic methods, and epidemiological issues, may affect vaccine efficacy. One example of geographic disparity is a group of randomized controlled trials of rotavirus vaccine, where high efficacy against severe rotavirus-confirmed gastroenteritis was seen in the developed world [2], [3] with lower efficacy against the same outcome among infants in developing countries [4], [5], [6]. Appropriately quantifying the value of vaccines was critical to the WHO decision on the use of rotavirus vaccine, and continues to be critical in promoting and sustaining vaccine programs, particularly in resource poor-settings where a strong argument must be made to justify prioritizing immunization programs among many other health priorities competing for scarce resources.

In June 2015, a group of experts discussed criteria to be considered to assess the full public health value (FPHV) of vaccination in addition to efficacy measured in individually randomized clinical trials [7]. It was clear for this group of experts that considering additional outcome measures (e.g., vaccine preventable disease incidence), and designs (e.g., vaccine probe studies and community randomized trials) were valuable, as was the consideration of indirect or community protection and economic and other non-health benefits of vaccines. They also considered that in addition to benefit-risk assessments based on the information collected through the traditional clinical development process, a substantial body of additional information is necessary to more fully inform policy and other required decision-making at the global, national and sub-national levels. Therefore, to assess the wider scope of vaccine benefits, there needs to be an enhanced expectation that studies – including licensing studies – incorporate measurement of these benefits; that greater connections are developed between partners who work on distinct but complementary aspects of vaccine valuation including health, economics, education, productivity, and economic gains; and that data and methods across these domains are shared widely across the vaccine community.

With such an enhanced paradigm and with a focus on low and middle-income countries (LMIC), alternative regulatory pathways could be considered that focus on conditional licensure of vaccines based on outcome results relevant to regulatory and public health decision-makers. This process could increase the development and introduction of vaccines in these countries. These issues will be particularly relevant to inform decision-making for vaccines on the near-term horizon such as those against malaria and dengue.

The components of this new paradigm having been defined [7], the Fondation Mérieux organized a second conference from 5–7 December 2016 (“Les Pensières” Conference Centre, Annecy-France), to evaluate the feasibility of an encompassing assessment of the FPHV of vaccines. The main objectives of the meeting were to advance discussions on the definition, evidence and communication of the FPHV of vaccines by:

  • challenging and refining the definition of what constitutes the FPHV of vaccination;

  • reviewing examples of FPHV with existing vaccines used in outbreak settings and others used in endemic disease settings;

  • proposing designs, measures, and outcomes for assessing the FPHV of vaccination in phase III trials and phase IV assessments and integrated/hybrid phase III/IV strategies;

  • applying these concepts to specific vaccines particularly those targeting malaria, dengue, Group B Streptococcus (GBS), Respiratory syncytial virus (RSV), Neisseria meningitidis B (NMB), and cholera, and;

  • strategizing on how to communicate the FPHV of vaccination to regulatory and program policy makers.

In this paper, we argue for as robust a measure as possible of the FPHV of vaccines to allow authorities to make accurate decisions on whether it will be efficient to invest in a particular vaccine for use in a particular setting and for a particular population, in the context of other public health interventions and programs remaining constant. As an example, the adoption of dengue vaccine should be considered in the context of an integrated management strategy while cholera vaccination should be considered in the context of clean water, sanitation, and hygiene.

Section snippets

Defining and assessing the FPHV of vaccines

Vaccine efficacy (VE) (Table 1), usually measured for etiologically-confirmed clinical outcomes, is often given the most weight among vaccine outcome measures considered in regulatory and policy recommendations. However, VE is not a static, robust, universal ‘true’ value as is commonly understood. Rather, it belongs within a list of measures that are useful for informing policy decisions. Indeed, VE can only be interpreted in the context of the population studied and the chosen trial design and

Rotavirus

Diarrheal disease caused by rotavirus is a public health problem in young children. The two available vaccines have shown significant impact in reducing all-cause acute gastroenteritis and rotavirus-related hospitalization [30] but also indirect benefits to older children and young adults in the USA [2], [3]. These vaccines conferred lower efficacy in the developing world [4], [5], [6]. While there were key differences in study design and methodology [31], the lower efficacy in developing

Discussion

Vaccines are an important contributor to the increase in life expectancy from less than 50 years in 1900 to more than 80 years now. During the last 15 years, there has been substantial advancement in vaccine innovation, a massive increase in the number of countries introducing several new vaccines into National Immunization Programs, and increased coverage with others, e.g., measles. Progress in introduction of three key vaccines supported by Gavi, the Vaccine Alliance (i.e., Hib in the form of

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.

List of speakers and chairs

Till Bärnighausen, Germany | Heidelberg University.

James Elston, UK | University of Leeds.

Janette Garin, Philippines | House of Representatives.

Bradford D. Gessner, France | Agence de Médecine Préventive.

Brian Greenwood, UK | London School of Hygiene & Tropical Medicine.

Ulla Griffiths, USA | UNICEF.

Ana Maria Henao-Restrepo, Switzerland | World Health Organization.

Raymond Hutubessy, Switzerland | WHO.

Safurah Jaafar, Malaysia | Ministry of Health Malaysia.

Nyoman Kandun, Indonesia | Indonesian

Acknowledgements

The authors express their gratitude to all speakers who shared their findings. Thanks are also due to Cindy Grasso (meeting coordinator) and the staff of the Mérieux Foundation conference centre for outstanding local organization.

Funding

The organization of this meeting was made possible through support to the Fondation Mérieux from Sanofi Pasteur.

The Fondation Mérieux compensated MSE, as a consultant, to compose the initial draft and to coordinate the co-authors’ reviews and approvals of this manuscript.

JL and VP are employees of the Fondation Mérieux, but received no additional compensation for their contributions to the conference or to this manuscript. All of the other co-authors, along with JL and VP, served on the

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