Lessons learned in shaping vaccine markets in low-income countries: vaccine market segment supported by GAVI

Health Policy and Planning
Volume 27 Issue 7   October 2012

Advance Access
Lessons learned in shaping vaccine markets in low-income countries: a review of the vaccine market segment supported by the GAVI Alliance
Shawn A.N. Gilchrist and Angeline Nanni

Objectives  The Global Alliance for Vaccines and Immunization (GAVI) anticipated that growing demand for new vaccines could sufficiently impact the vaccines market to allow low-income countries (LICs) to self-finance new vaccines. But the time required to lower vaccine prices was underestimated and the amount that prices would decline overestimated. To better understand how prices in the LIC vaccine market can be impacted, the vaccine market was retrospectively examined.

Design  GAVI archives and the published literature on the vaccine markets in LICs were reviewed for the purpose of identifying GAVI’s early assumptions for the evolution of vaccine prices, and contrasting these retrospectively with actual outcomes.

Results  The prices in Phases I and II of GAVI-supported vaccines failed to decline to a desirable level within a projected 5-year timeframe. GAVI-eligible countries were unable to sustain newly introduced vaccines without prolonged donor support. Two key lessons can be applied to future vaccine market-shaping strategies: (1) accurate demand forecasting together with committed donor funding can increase supply to the LIC vaccines market, but even greater strides can be made to increase the certainty of purchase; and (2) the expected time to lower prices took much longer than 5 years; market competition is inherently linked to the development time for new vaccines—a minimum of 5–10 or more years. Other factors that can lower vaccine prices include: large-scale production or alternate financing mechanisms that can hasten vaccine price maturation.

Conclusions  The impacts of competition on vaccine prices in the LIC new-vaccines market occurred after almost 10 years. The time for research and development, acquisition of technological know-how and to scale production must be accounted for to more accurately predict significant declines on vaccine prices. Alternate financing mechanisms and the use of purchase agreements should also be considered for lowering prices when planning new vaccine introductions.

Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1

The Lancet Infectious Disease
Dec 2012  Volume 12  Number 12   p897 – 984

Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1
Jennifer A Whitaker, Nadine G Rouphael, Srilatha Edupuganti, Lilin Lai, Mark J Mulligan

HIV and hepatitis B virus co-infection leads to substantially increased morbidity and mortality compared with either infection alone. Immunisation with hepatitis B virus vaccine is the most effective way to prevent the infection in people with HIV; however, these patients have decreased vaccine responses and a short duration of protection compared with immunocompetent individuals. Control of HIV replication with highly active antiretroviral therapy and increased CD4 cell counts are associated with improved immune responses to hepatitis B vaccination. New vaccination strategies, such as increased vaccine dose, use of the intradermal route, and addition of adjuvants, could improve response rates in adults with HIV.

Longitudinal Investigation of Public Trust in Institutions Relative to the 2009 H1N1 Pandemic in Switzerland

PLoS One
[Accessed 24 November 2012]

Longitudinal Investigation of Public Trust in Institutions Relative to the 2009 H1N1 Pandemic in Switzerland
Adrian Bangerter, Franciska Krings, Audrey Mouton, Ingrid Gilles, Eva G. T. Green, Alain Clémence
PLoS ONE: Research Article, published 21 Nov 2012 10.1371/journal.pone.0049806

The 2009 H1N1 pandemic left a legacy of mistrust in the public relative to how outbreaks of emerging infectious diseases are managed. To prepare for future outbreaks, it is crucial to explore the phenomenon of public trust in the institutions responsible for managing disease outbreaks. We investigated the evolution of public trust in institutions during and after the 2009 pandemic in Switzerland. We also explored respondents’ perceptions of the prevention campaign and the roles of the government and media.

Methodology/Principal Findings
A two-wave longitudinal survey was mailed to 2,400 members of the Swiss public. Wave 1 was in Spring 2009. Wave 2 was in Spring 2010. Six hundred and two participants responded in both waves. Participants indicated moderate to high levels of trust in medical organizations, the WHO, the Swiss government, the pharmaceutical industry, and the EU. On the other hand, trust in the media was low. Moreover, trust in almost all institutions decreased over time. Participants were satisfied with the amount of information received and indicated having followed official recommendations, but widespread concerns about the vaccine were evident. A large majority of participants agreed the vaccine might have unknown or undesirable side effects. Perceptions of the government’s and the media’s role in handling the outbreak were characterized by a substantial degree of skepticism and mistrust.

Results show clear patterns of skepticism and mistrust on the part of the public relative to various institutions and their actions. Results underscore the importance of systematically investigating trust of the public relative to epidemics. Moreover, studies investigating the evolution of the public’s memories of the pandemic over the coming years may be important to understand reactions to future pandemics. A systematic research program on trust can inform public health communication campaigns, enabling tailored communication initiatives.

Economic Burden of Human Papillomavirus-Related Diseases in Italy

PLoS One
[Accessed 24 November 2012]

Economic Burden of Human Papillomavirus-Related Diseases in Italy
Gianluca Baio, Alessandro Capone, Andrea Marcellusi, Francesco Saverio Mennini, Giampiero Favato
PLoS ONE: Research Article, published 21 Nov 2012 10.1371/journal.pone.0049699

Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection.

For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection.

The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy.

The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials

PLoS Medicine
(Accessed 24 November 2012)

The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials
Charles Weijer, Jeremy M. Grimshaw, Martin P. Eccles, Andrew D. McRae, Angela White, Jamie C. Brehaut, Monica Taljaard, Ottawa Ethics of Cluster Randomized Trials Consensus Group published 20 Nov 2012

Summary Points
– In cluster randomized trials (CRTs), the units of allocation, intervention, and outcome measurement may differ within a single trial. As a result of the unique design of CRTs, the interpretation of existing research ethics guidelines is complicated.

– The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials aims to provide researchers and research ethics committees (RECs) with detailed guidance on the ethical design, conduct, and review of CRTs.

– A five-year mixed methods research project explored the ethical challenges of CRTs. Empirical studies documented the reporting of ethical issues in published CRTs, interviewed experienced trialists, and surveyed trialists and REC chairs. The ethical issues identified were explored in a series of background papers that provided detailed ethical analyses and policy options, and a panel of experts using a systematic process developed a consensus statement.

– The Ottawa Statement sets out 15 recommendations for the ethical design and conduct of CRTs. The recommendations provide guidance on the justification of a cluster randomized design, the need for REC review, the identification of research participants, obtaining informed consent, the role of gatekeepers in protecting group interests, the assessment of benefits and harms, and the protection of vulnerable participants.

Self-boosting vaccines and their implications for herd immunity

PNAS – Proceedings of the National Academy of Sciences of the United States
of America

(Accessed 24 November 2012)

Biological Sciences – Population Biology:
Self-boosting vaccines and their implications for herd immunity
Nimalan Arinaminpathy, Jennie S. Lavine, and Bryan T. Grenfell
PNAS 2012 ; published ahead of print November 19, 2012, doi:10.1073/pnas.1209683109

Advances in vaccine technology over the past two centuries have facilitated far-reaching impact in the control of many infections, and today’s emerging vaccines could likewise open new opportunities in the control of several diseases. Here we consider the potential, population-level effects of a particular class of emerging vaccines that use specific viral vectors to establish long-term, intermittent antigen presentation within a vaccinated host: in essence, “self-boosting” vaccines. In particular, we use mathematical models to explore the potential role of such vaccines in situations where current immunization raises only relatively short-lived protection. Vaccination programs in such cases are generally limited in their ability to raise lasting herd immunity. Moreover, in certain cases mass vaccination can have the counterproductive effect of allowing an increase in severe disease, through reducing opportunities for immunity to be boosted through natural exposure to infection. Such dynamics have been proposed, for example, in relation to pertussis and varicella-zoster virus. In this context we show how self-boosting vaccines could open qualitatively new opportunities, for example by broadening the effective duration of herd immunity that can be achieved with currently used immunogens. At intermediate rates of self-boosting, these vaccines also alleviate the potential counterproductive effects of mass vaccination, through compensating for losses in natural boosting. Importantly, however, we also show how sufficiently high boosting rates may introduce a new regime of unintended consequences, wherein the unvaccinated bear an increased disease burden. Finally, we discuss important caveats and data needs arising from this work.

BMGF: prevention of maternal and early infant influenza in resource-limited settings

Volume 30, Issue 50, Pages 7131-7342 (26 November 2012)

Meeting Report
Translating vaccine policy into action: A report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings
Pages 7134-7140
Justin R. Ortiz, Kathleen M. Neuzil, Vincent I. Ahonkhai, Bruce G. Gellin, David M. Salisbury, Jennifer S. Read, Richard A. Adegbola, Jon S. Abramson

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life.

In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success.

We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant women during the 2009 influenza pandemic. We conclude with an analysis of data gaps and necessary activities to facilitate implementation of maternal influenza immunization programs in resource-limited settings.