A Financial and Global Demand Analysis to Inform Decisions for Funding and Clinical Development of Group B Streptococcus Vaccines for Pregnant Women.

BACKGROUND: Despite group B Streptococcus (GBS) being a leading cause of maternal and infant morbidity and mortality, no vaccine is currently available. To inform vaccine developers, countries, and funders, we analyzed the key factors likely to influence the demand for a GBS vaccine and the long-term financial sustainability for a vaccine developer. METHODS: Using population-based forecasting, we estimated the demand for a GBS vaccine; using a discounted cash flow model we estimated the financial viability for a vaccine developer. RESULTS: Demand for this vaccine can be significant if countries adopt policy recommendations for use, in particular, the largest ones, most of which have a burden that justifies use of the vaccine, and if financing for the vaccine is made available either by countries or by funding mechanisms such as Gavi, the Vaccine Alliance. CONCLUSIONS: This analysis suggests the potential for financial and commercial viability for a vaccine developer pursuing the commercialization of a GBS vaccine. Risks exists in relation to the clinical trial design and costs, the level of competition, countries' ability to pay, the administration schedule, and the availability of policies that encourage use of the vaccine. To reduce those risks and ensure equitable access to a GBS vaccine, the role of donors or financers can prove very important, as can a coordinated operational research agenda that aims at clarifying those areas of uncertainty.

Human leishmaniasis vaccines: Use cases, target population and potential global demand.

The development of vaccines against one or all forms of human leishmaniasis remains hampered by a paucity of investment, at least in part resulting from the lack of well-evidenced and agreed estimates of vaccine demand. Starting from the definition of 4 main use cases (prevention of visceral leishmaniasis, prevention of cutaneous leishmaniasis, prevention of post-kala-azar dermal leishmaniasis and treatment of post-kala-azar dermal leishmaniasis), we have estimated the size of each target population, focusing on those endemic countries where incidence levels are sufficiently high to justify decisions to adopt a vaccine. We assumed a dual vaccine delivery strategy, including a wide age-range catch-up campaign before the start of routine immunisation. Vaccine characteristics and delivery parameters reflective of a target product profile and the likely duration of the clinical development effort were considered in forecasting the demand for each of the four indications. Over a period of 10 years, this demand is forecasted to range from 300-830 million doses for a vaccine preventing visceral leishmaniasis and 557-1400 million doses for a vaccine preventing cutaneous leishmaniasis under the different scenarios we simulated. In a scenario with an effective prophylactic visceral leishmaniasis vaccine, demand for use to prevent or treat post-kala-azar dermal leishmaniasis would be more limited (over the 10 years ~160,000 doses for prevention and ~7,000 doses for treatment). Demand would rise to exceed 330,000 doses, however, in the absence of an effective vaccine for visceral leishmaniasis. Because of the sizeable demand and potential for public health impact, a single-indication prophylactic vaccine for visceral or cutaneous leishmaniasis, and even more so a cross-protective prophylactic vaccine could attract the interest of commercial developers. Continuous refinement of these first-of-their kind estimates and confirmation of country willingness and ability to pay will be paramount to inform the decisions of policy makers and developers in relation to a leishmaniasis vaccine. Positive decisions can provide a much-needed contribution towards the achievement of global leishmaniasis control.

New vaccine introductions: assessing the impact and the opportunities for immunization and health systems strengthening.

In 2010, global immunization partners posed the question, "Do new vaccine introductions (NVIs) have positive or negative impacts on immunization and health systems of countries?" An Ad-hoc Working Group was formed for WHO's Strategic Advisory Group of Experts on immunization (SAGE) to examine this question through five approaches: a published literature review, a grey literature review, in-depth interviews with regional and country immunization staff, in-depth studies of recent NVIs in 3 countries, and a statistical analysis of the impact of NVI on DTP3 coverage in 176 countries. The WHO Health System Framework of building blocks was used to organize the analysis of these data to assess potential areas of impact of NVI on health systems. In April 2012, the Ad-hoc Working Group presented its findings to SAGE. While reductions in disease burden and improvements in disease and adverse events surveillance, training, cold chain and logistics capacity and injection safety were commonly documented as beneficial impacts, opportunities for strengthening the broader health system were consistently missed during NVI. Weaknesses in planning for human and financial resource needs were highlighted as a concern. Where positive impacts on health systems following NVI occurred, these were often in areas where detailed technical guidance or tools and adequate financing were available. SAGE supported the Ad-hoc Working Group's conclusion that future NVI should explicitly plan to optimize and document the impact of NVI on broader health systems. Furthermore, opportunities for improving integration of delivery of immunization services, commodities, and messages with other parts of the health system should be actively sought with the recognition that integration is a bidirectional process. To avoid the gaps in planning for NVI that can compromise existing immunization and health systems, donors and partners should provide sufficient and timely support to facilitate country planning. Areas for future research were also identified. Finally, to support countries in using NVI as an opportunity to strengthen immunization and health systems, the WHO guidance for countries on new vaccine introduction is being updated to reflect ways this might be accomplished.

The impact of new vaccine introduction on immunization and health systems: a review of the published literature.

We conducted a systematic review of the published literature to examine the impact of new vaccine introduction on countries' immunization and broader health systems. Six publication databases were searched using 104 vaccine and health system-related search terms. The search yielded 15,795 unique articles dating from December 31, 1911 to September 29, 2010. Based on review of the title and abstract, 654 (4%) of these articles were found to be potentially relevant and were referred for full review. After full review, 130 articles were found to be relevant and included in the analysis. These articles represented vaccines introduced to protect against 10 different diseases (hepatitis A, hepatitis B, Haemophilus influenzae type b disease, human papilloma virus infection, influenza, Japanese encephalitis, meningococcal meningitis, Streptococcus pneumoniae disease, rotavirus diarrhea and typhoid), in various formulations and combinations. Most reviewed articles (97 [75%]) reported experiences in high-income countries. New vaccine introduction was most efficient when the vaccine was introduced into an existing delivery platform and when introduced in combination with a vaccine already in the routine childhood immunization schedule (i.e., as a combination vaccine). New vaccine introduction did not impact coverage of vaccines already included in the routine childhood immunization schedule. The need for increased cold chain capacity was frequently reported. New vaccines facilitated the introduction and widespread use of auto-disable syringes into the immunization and the broader health systems. The importance of training and education for health care workers and social mobilization was frequently noted. There was evidence in high-income countries that new vaccine introduction was associated with reduced health-care costs. Future evaluations of new vaccine introductions should include the systematic and objective assessment of the impacts on a country's immunization system and broader health system, especially in lower-income countries.