Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study.

BACKGROUND: The Coalition for Epidemic Preparedness Innovations was established in 2016, to develop vaccines that can contribute to preparedness for outbreaks of epidemic infectious diseases. Evidence on vaccine development costs for such diseases is scarce. Our goal was to estimate the minimum cost for achieving vaccine research and development preparedness targets in a portfolio of 11 epidemic infectious diseases, accounting for vaccine pipeline constraints and uncertainty in research and development preparedness outcomes. METHODS: We assembled a pipeline of 224 vaccine candidates from preclinical through to phase 2 for 11 priority epidemic infectious diseases. We used a linear regression model to identify drivers of development costs from preclinical through to end of phase 2a. Drawing from published estimates of vaccine research and development probabilities of success, we simulated costs for advancing these 224 vaccine candidates through to the end of phase 2a. We combined these findings to determine minimum costs for progressing at least one vaccine through to the end of phase 2a per epidemic infectious disease by means of a stochastic optimisation model. FINDINGS: The cost of developing a single epidemic infectious disease vaccine from preclinical trials through to end of phase 2a is US$31-68 million (US$14-159 million range), assuming no risk of failure. We found that previous licensure experience and indirect costs are upward drivers of research and development costs. Accounting for probability of success, the average cost of successfully advancing at least one epidemic infectious disease vaccine through to the end of phase 2a can vary from US$84-112 million ($23 million-$295 million range) starting from phase 2 to $319-469 million ($137 million-$1·1 billion range) starting from preclinical. This cost includes the cumulative cost of failed vaccine candidates through the research and development process. Assuming these candidates and funding were made available, progressing at least one vaccine through to the end of phase 2a for each of the 11 epidemic infectious diseases would cost a minimum of $2·8-3·7 billion ($1·2 billion-$8·4 billion range). INTERPRETATION: Our analysis provides new evidence on vaccine research and development pipelines and associated costs for 11 epidemic infectious diseases, highlighting both funding needs and research and development gaps for achieving vaccine research and development preparedness targets. FUNDING: This work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme GLOBVAC.

Allocating external financing for health: a discrete choice experiment of stakeholder preferences.

Most donors of external financing for health use allocation policies to determine which countries are eligible to receive financial support and how much support each should receive. Currently, most of these policies place a great deal of weight on income per capita as a determinant of aid allocation but there is increasing interest in putting more weight on other country characteristics in the design of such policies. It is unclear, however, how much weight should be placed on other country characteristics. Using an online discrete choice experiment designed to elicit preferences over country characteristics to guide decisions about the allocation of external financing for health, we find that stakeholders assign a great deal of importance to health inequalities and the burden of disease but put very little weight on income per capita. We also find considerable variation in preferences across stakeholders, with people from low- and middle-income countries putting more weight on the burden of disease and people from high-income countries putting more weight on health inequalities. These findings suggest that stakeholders put more weight on burden of disease and health inequalities than on income per capita in evaluating which countries should received external financing for health and that that people living in aid recipient may have different preferences than people living in donor countries. Donors may wish to take these differences in preferences in mind if they are reconsidering their aid allocation policies.

New approaches to ranking countries for the allocation of development assistance for health: choices, indicators and implications.

The distributions of income and health within and across countries are changing. This challenges the way donors allocate development assistance for health (DAH) and particularly the role of gross national income per capita (GNIpc) in classifying countries to determine whether countries are eligible to receive assistance and how much they receive. Informed by a literature review and stakeholder consultations and interviews, we developed a stepwise approach to the design and assessment of country classification frameworks for the allocation of DAH, with emphasis on critical value choices. We devised 25 frameworks, all which combined GNIpc and at least one other indicator into an index. Indicators were selected and assessed based on relevance, salience, validity, consistency, and availability and timeliness, where relevance concerned the extent to which the indicator represented country's health needs, domestic capacity, the expected impact of DAH, or equity. We assessed how the use of the different frameworks changed the rankings of low- and middle-income countries relative to a country's ranking based on GNIpc alone. We found that stakeholders generally considered needs to be the most important concern to be captured by classification frameworks, followed by inequality, expected impact and domestic capacity. We further found that integrating a health-needs indicator with GNIpc makes a significant difference for many countries and country categories-and especially middle-income countries with high burden of unmet health needs-while the choice of specific indicator makes less difference. This together with assessments of relevance, salience, validity, consistency, and availability and timeliness suggest that donors have reasons to include a health-needs indicator in the initial classification of countries. It specifically suggests that life expectancy and disability-adjusted life year rate are indicators worth considering. Indicators related to other concerns may be mainly relevant at different stages of the decision-making process, require better data, or both.

Gavi's policy steers country ownership and self-financing of immunization.

This commentary examines the 2014 NIPH evaluation of Gavi's co-financing policy and comments on the appropriateness of the subsequent and most significant policy changes taking effect in 2016.

Scaling up of HIV treatment for men who have sex with men in Bangkok: a modelling and costing study.

BACKGROUND: Despite the high prevalence of HIV in men who have sex with men (MSM) in Bangkok, little investment in HIV prevention for MSM has been made. HIV testing and treatment coverage remains low. Through a pragmatic programme-planning approach, we assess possible service linkage and provision of HIV testing and antiretroviral treatment (ART) to MSM in Bangkok, and the most cost-effective scale-up strategy. METHODS: We obtained epidemiological and service capacity data from the Thai National Health Security Office database for 2011. We surveyed 13 representative medical facilities for detailed operational costs of HIV-related services for sexually active MSM (defined as having sex with men in the past 12 months) in metropolitan Bangkok. We estimated the costs of various ART scale-up scenarios, accounting for geographical accessibility across Bangkok. We used an HIV transmission population-based model to assess the cost-effectiveness of the scenarios. FINDINGS: For present HIV testing (23% [95% CI 17-36] of MSM at high risk in 2011) and ART provision (20% of treatment-eligible MSM at high risk on ART in 2011) to be sustained, a US$73·8 million ($51·0 million to $97·0 million) investment during the next decade would be needed, which would link an extra 43,000 (27,900-58,000) MSM at high risk to HIV testing and 5100 (3500-6700) to ART, achieving an ART coverage of 44% for MSM at high risk in 2022. An additional $55·3 million investment would link an extra 46,700 (30,300-63,200) MSM to HIV testing and 12,600 (8800-16,600) to ART, achieving universal ART coverage of this population by 2022. This increased investment is achievable within present infrastructure capacity. Consequently, an estimated 5100 (3600-6700) HIV-related deaths and 3700 (2600-4900) new infections could be averted in MSM by 2022, corresponding to a 53% reduction in deaths and a 35% reduction in infections from 2012 levels. The expansion would cost an estimated $10,809 (9071-13,274) for each HIV-related death, $14,783 (12,389-17,960) per new infection averted, and $351 (290-424) per disability-adjusted life-year averted. INTERPRETATION: Spare capacity in Bangkok's medical facilities can be used to expand ART access for MSM with large epidemiological benefits. The expansion needs increased funding directed to MSM services, but given the epidemiological trends, is probably cost effective. Our modelling approach and outcomes are likely to be applicable to other settings. FUNDING: World Bank Group and Australian National Health and Medical Research Council.

How are health research priorities set in low and middle income countries? A systematic review of published reports.

BACKGROUND: Priority setting is increasingly recognised as essential for directing finite resources to support research that maximizes public health benefits and drives health equity. Priority setting processes have been undertaken in a number of low- and middle-income country (LMIC) settings, using a variety of methods. We undertook a critical review of reports of these processes. METHODS AND FINDINGS: We searched electronic databases and online for peer reviewed and non-peer reviewed literature. We found 91 initiatives that met inclusion criteria. The majority took place at the global level (46%). For regional or national initiatives, most focused on Sub Saharan Africa (49%), followed by East Asia and Pacific (20%) and Latin America and the Caribbean (18%). A quarter of initiatives aimed to cover all areas of health research, with a further 20% covering communicable diseases. The most frequently used process was a conference or workshop to determine priorities (24%), followed by the Child Health and Nutrition Initiative (CHNRI) method (18%). The majority were initiated by an international organization or collaboration (46%). Researchers and government were the most frequently represented stakeholders. There was limited evidence of any implementation or follow-up strategies. Challenges in priority setting included engagement with stakeholders, data availability, and capacity constraints. CONCLUSIONS: Health research priority setting (HRPS) has been undertaken in a variety of LMIC settings. While not consistently used, the application of established methods provides a means of identifying health research priorities in a repeatable and transparent manner. In the absence of published information on implementation or evaluation, it is not possible to assess what the impact and effectiveness of health research priority setting may have been.

Spending of HIV resources in Asia and Eastern Europe: systematic review reveals the need to shift funding allocations towards priority populations.

INTRODUCTION: It is increasingly important to prioritize the most cost-effective HIV interventions. We sought to summarize the evidence on which types of interventions provide the best value for money in regions with concentrated HIV epidemics. METHODS: We conducted a systematic review of peer-reviewed and grey literature reporting measurements of cost-effectiveness or cost-benefit for HIV/AIDS interventions in Asia and Eastern Europe. We also collated HIV/AIDS spending assessment data from case-study countries in the region. RESULTS: We identified 91 studies for inclusion, 47 of which were from peer-reviewed journals. Generally, in concentrated settings, prevention of mother-to-child transmission programmes and prevention programmes targeting people who inject drugs and sex workers had lower incremental cost-effectiveness ratios than programmes aimed at the general population. The few studies evaluating programmes targeting men who have sex with men indicate moderate cost-effectiveness. Collation of prevention programme spending data from 12 countries in the region (none of which had generalized epidemics) indicated that resources for the general population/non-targeted was greater than 30% for eight countries and greater than 50% for five countries. CONCLUSIONS: There is a misalignment between national spending on HIV/AIDS responses and the most affected populations across the region. In concentrated epidemics, scarce funding should be directed more towards most-at-risk populations. Reaching consensus on general principles of cost-effectiveness of programmes by epidemic settings is difficult due to inconsistent evaluation approaches. Adopting a standard costing, impact evaluation, benefits calculation, analysis and reporting framework would enable cross comparisons and improve HIV resource prioritization and allocation.