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In this guest post Tom Harmon, senior policy analyst at the International AIDS Vaccine Initiative (IAVI), highlights a new analysis exploring the critical role of a vaccine in ending AIDS. Photo credit: IAVI When we talk about ending AIDS, what do we mean? The last dozen years have brought tremendous strides in reducing new HIV infections in low- and middle-income countries (LMICs), expanding lifesaving treatment to almost 16 million people living with HIV, and implementing programs to address the epidemic in populations at especially high risk, including women and girls. But we must continue to push for progress in treatment and prevention. The 2 million new infections in 2014 remain far too high, and almost 60 percent of people needing treatment are not getting it. So, when we talk about conclusively and durably ending AIDS and ensuring that it does not bounce back, our experience with other infectious diseases shows that a preventive vaccine will be necessary. The global effort to develop an AIDS vaccine has also recently experienced significant successes and steps forward. For example, we’ve never before seen such a diversity of approaches and partners, with follow-on trials based on the first candidate to show modest efficacy slated to begin later this year in South Africa, exciting new insights toward generating protective antibodies against HIV, and promising approaches toward inducing cellular immune responses that could control HIV infection. Still, there are more far-reaching questions we’re asked today by policymakers, advocates, communities, and even researchers themselves: What would the global response look like if an AIDS vaccine was available? How effective would it need to be? Would it be cost-effective and affordable? A new article, published in PLoS ONE aims to answer some of these crucial questions. The result of a collaboration between IAVI, Avenir Health, and AVAC that builds on work by UNAIDS, this model specifically explores a vaccine’s potential value in terms of preventing HIV infections in LMICs. We analyzed a vaccine’s potential impact depending on how well the world can achieve ambitious HIV and AIDS program objectives, how effectively it can prevent HIV infection, and how it can add to a response that also includes pre-exposure prophylaxis and treatment as prevention. We also looked at cost scenarios to see how a vaccine would stand up to cost-effectiveness criteria used by the World Health Organization to guide the introduction of new health technologies. Despite the potential for today’s tools to have a substantial impact on the epidemic, our results show that a vaccine is a critical piece to ending AIDS. Under our base scenario, a vaccine of 70 percent efficacy with strong uptake would reduce HIV infections in LMICs by 44 percent in its first 10 years and by 65 percent in 25 years, ultimately averting tens of millions of infections and saving millions of lives. Reduction of new annual HIV infections with PrEP, TasP and vaccination added individually and in combination to the Full Scale-up of IFE between 2015 and 2070. A vaccine would be impactful and cost-effective even at lower efficacy levels and costs far higher than many of today’s vaccines. Increasing a vaccine’s efficacy, ensuring it protects for a longer period of time, reducing the number of doses, lowering the cost of a dose, and more effectively rolling it out are all factors that would increase a vaccine’s impact and its value. Such a vaccine could cut the number of people needing treatment in half by the year 2070, and eventually reduce the total cost of fighting AIDS in LMICs even when the additional cost of implementing the vaccination program is included. While these data provide a powerful illustration of a vaccine’s potential value, we acknowledge and welcome discussions of its intrinsic limitations, which reflect the areas the AIDS vaccine field and future program implementers will need to tackle as we research, develop, and ultimately deliver a vaccine to the people who need it most. Such an analysis helps explore the parameters that determine the medical and economic impact and value of a future AIDS vaccine as part of the comprehensive HIV and AIDS response. This data can be a useful guide for research portfolio decisions as new candidates move closer to efficacy trials. In many ways these projections are as much a vaccine development and delivery “to-do list” as they are a crystal ball for what the future holds. A few weeks ago, the US Centers for Disease Control and Prevention organized a Grand Rounds presentation on how models are used to guide pandemic responses. This interesting panel was closed by Dr. Richard Hatchett, chief medical officer and deputy director for strategic sciences at the US Biomedical Advanced Research and Development Authority, who cited modeler Steven Bankes’ use of campfires as an analogy for predictive models, in that their value goes beyond their primary deliverable (be it light, heat, or data), as they just as importantly provide a “gathering place” for discussion between stakeholders. Our new model can perform just such a dual function, adding valuable context for a vaccine’s future role in ending the AIDS epidemic which has ravaged so many communities, while stimulating conversations and new questions on what we need to do in the real world to turn theory to impact.

Seated woman holding baby bundled in a blanket East London, Tutura Clinic, Sep 29, 2009 (Photo: PATH/Wendy Stone) Many of the 15 million babies born premature each year struggle with hypothermia and need help to stay warm. To address this problem, researchers at Johns Hopkins University and George Mason University developed a thermal blanket that uses the chemical substance found in hand warmers and pain patches. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) is currently testing the blanket to determine its acceptability and feasibility among mothers and health care providers in Bangladesh and initial results suggest that it is easy-to-use, portable, and can be affordably produced using local materials. Next, the team will incorporate feedback on the blanket’s design and use from the study and a stakeholder’s workshop and will test the efficacy of the blanket in reducing newborn mortality. In India, where there are only seven doctors for every 10,000 people—compared to a global average of 13.9—and where nearly six times as many critical care doctors are needed, electronic intensive care units (eICUs) are expanding access to quality, intensive care. In these eICUs, critical care specialists monitor patients and their vital signs and as needed, provide instructions to local physicians—who may not have any intensive care experience—remotely. Across the country, there are currently 3,000 eICU “beds,” and a 15–20 percent is expected annually. Fortis Healthcare, a chain of hospitals that currently monitors 350 patients, estimates that they save 25 lives per month. While the cost of monitoring patients remotely is only US$10–30 per day, the standard cost of critical care within the hospital ($200 per day) remains, and thus, access to the technology remains limited to those who can afford it. The United States, European Union, and World Health Organization (WHO) are seeking to expedite Zika virus research and development (R&D) through financing and innovative regulatory mechanisms. The White House is calling on the US Congress to provide $1.8 billion in funding to combat Zika, including $200 million specifically for vaccine and diagnostic R&D. The request also includes funding for the US Agency for International Development to incentivize R&D through public-private partnerships, advanced market commitments, or volume guarantees. Meanwhile, legislation has been introduced in both the House and Senate to add Zika virus to the list of diseases eligible for the US Food and Drug Administration’s Priority Review Voucher program, through which a pharmaceutical company is granted a voucher (worth up to $350 million) for expedited review of a future drug as a reward for successfully sponsoring the review of a drug for a neglected disease. Meanwhile, the European Medicines Agency has established a task force to advise on scientific and regulatory issues—including clinical trial design, manufacturing, and post-market surveillance—for tools to prevent, detect, and treat Zika. The European Commission is offering $10 million for Zika vaccine R&D, using existing funding for vaccine development through Horizon 2020, which promotes research and innovation across sectors. The WHO plans to use its Emergency Use Assessment and Listing procedures to rapidly evaluate Zika products for quality, efficacy, and safety. This mechanism is particularly invaluable as United Nations agencies and many nongovernmental organizations rely on WHO evaluations when making procurement decisions.

WHO EB meets in Geneva. Photo: GHTC/Jana ArmstrongThere’s an old adage about political negotiating: “You need to be in the room when things are happening if you want to have an impact.” At its recent meeting, the World Health Organization (WHO) Executive Board (EB) discussed precisely who would be allowed in the room in the future under the proposed new Framework for Engagement with Non-State Actors (FENSA), which, if passed by the World Health Assembly (WHA), would set strict new rules and processes for WHO to follow in engaging with non-state actors (NSA)—including nongovernmental organizations (NGOs), civil society organizations (CSOs), the private sector, and philanthropic foundations. These new policies impact everything from who is allowed to participate in governance meetings to the ways WHO can collaborate with local NGOs. To provide some context for the proposed changes, below is an overview of the current rules, the proposed new regulations, and some of the implications of particular concern for the global health research and development (R&D) world.Current rules governing engagement with NSAs The current rules governing WHO’s collaboration with NSAs derive from “Principles Governing Relations Between the World Health Organization and Nongovernmental Organizations.” The Principles recognize three levels of relations between WHO and NSAs: informal, working, and official. Informal relations consist of “…exchanges of information and reciprocal participation in technical meetings” and are designed to build a platform of shared priorities. They can continue on an ad-hoc basis for as long as necessary without any written agreement.If the relationship elevates to the level of specific joint programming and activities, WHO and the NSA can enter into a 2-year period of working relations. The two organizations exchange formal letters of commitment and agree to evaluate the outcome of the collaboration at the end of the joint activities. These types of collaboration do not require any decisions by the EB and can occur with WHO Secretariat staff approval; they do not grant any formal participation rights at the EB or WHA.To receive formal recognition and participation rights at the EB and WHA, an NSA must complete a successful period of working relations and submit an application to the EB. If admitted into formal relations, the NSA’s relationship with WHO is then subject to review every three years. If the application is rejected, the NSA cannot reapply until it has completed another period of working relations.Proposed new regulations The new proposed FENSA rules take a far different approach. Rather than recognizing three different categories of relations, it features only two: official relations and “engagement.” Unlike the current regulations, however, it does specify different rules of engagement depending on the type of NSA; NGOs/nonprofits are treated differently than philanthropic foundations, which are treated differently than academic institutions, which are in turn treated differently than the private sector. Of particular note for the R&D community, private-sector entities would be barred from official relations, as would any entities not “at arm’s length” from commercial sponsors or members. This could be interpreted to include some product development partnerships.Under FENSA, WHO would be required to create a publicly-available online register of every NSA it engages with at the global, regional, or country level. A pilot version of this register is currently available here. Each NSA that wished to engage with WHO would be required to populate all of the information shown in the link above as well as a to-be-determined section detailing the precise nature and funding of the engagement. For the purpose of registration requirements, engagements are defined as: participation in meetings, donation of resources, information/evidence sharing, advocacy efforts, and technical or programmatic collaboration. Essentially, as currently written, this category requires registration for almost any type of collaboration.When an organization proposes engagement(s), WHO Secretariat staff would be required to review both the organization’s information and the proposed activity in the register, as well as conduct a full due diligence assessment on risk management and potential conflicts of interest. Only after these processes have completed would the activity move forward. The staff burden of these processes is hard to overstate; the European WHO region had over 5,000 individual engagements with over 1,500 NSAs in 2014 alone.As shocking as it sounds, all of the above scrutiny would be required for simple “engagement,” not for official relations. In order to guarantee the right of representation at EB and WHA meetings, an organization would still need to submit a separate application with even more extensive documentation.Implications for the health R&D community Ultimately, FENSA, if implemented as it currently stands, does not seem likely to fix any problems, while it would likely create additional hurdles for the R&D community by: Greatly hindering the ability of WHO to collaborate with outside organizations by imposing a burdensome registration and review process for every type of engagement (no matter how small or informal). Potentially disenfranchising significant sectors of the global health R&D community by imposing stricter requirements that might redefine some product development partnerships as private-sector organizations that are not entitled to representation. The WHO working group revising FENSA will meet again in early April to attempt to reach an agreement so that they can present a consensus resolution to the WHA in May. We will be following the process very closely, and will provide further updates on this blog as they happen.

In this guest post, Anna Doubell, an analyst at Policy Cures, writes about the findings of this year’s G-FINDER report on neglected disease research and development (R&D). Supporting data from the report was released this week and is now available online through the G-FINDER public search tool. Photo: PATH/Patrick McKern The West African Ebola outbreak featured prominently on the front pages of newspapers globally in 2014, reminding us of the devastating impact that an infectious disease can have on communities when the required vaccines, treatments, and diagnostic tools don’t exist, and the health systems to utilize them are severely lacking. However, Ebola is only one of many infectious diseases for which there are a lack of adequate products. The G-FINDER survey, conducted by Policy Cures, collects data about funding for neglected disease R&D from over two hundred organizations each year. This year’s report, published in December, and the supporting data, released this week, highlight funding trends and gaps for R&D to develop new health technologies for neglected diseases, which can help governments, philanthropic organizations, and industry make informed decisions. Expansion of scope to include Ebola In response to the 2014 outbreak, we included Ebola in the 2015 G-FINDER survey scope for the first time, and the data published this week provides the first detailed picture of global funding for Ebola R&D. In many ways Ebola is a prototypical neglected disease: low-income countries (Sierra Leone, Guinea and Liberia) bore the brunt of the epidemic; no proven vaccines, antiviral drugs, or field-suitable diagnostic tests existed for Ebola when the outbreak began; and despite the existence of some bioterror-related research programmes, there had been insufficient commercial incentives to attract enough R&D investment from industry to develop products through to registration. But the rapid spread and potential global impact of Ebola led to unprecedented levels of attention and new investments in R&D. Grounds for optimism? The response to the outbreak showed that funders can rapidly mobilize money for R&D into neglected diseases in times of crisis. The 2015 G-FINDER survey found that US$165 million was invested in Ebola R&D in 2014, which is remarkable given that the outbreak was only declared a public health emergency in August of that year. This investment made Ebola the fifth best-funded neglected disease, behind only HIV and AIDS, malaria, tuberculosis (TB), and diarrheal diseases. Nearly three quarters of Ebola investment came from the public sector (most of it from the US government), followed by the pharmaceutical industry, providing 21 percent of all funding. The mobilization of resources, both human and financial, resulted in clinical trials for drugs and vaccines being launched in record time,1 showing what might be possible for other neglected diseases, many of which cause more deaths in developing countries every year than did Ebola. Bacterial pneumonia and meningitis, for instance, kill more than 750,000 people in the developing world each year—compared to just over 11,000 deaths in two years from the recent Ebola outbreak—and yet in 2014 these diseases received less than half the R&D funding that went to Ebola. Caution still required This impressive response raises a number of questions. Will investment in Ebola R&D continue as the epidemic comes to an end, and will this funding be sufficient to support the products currently in development through to registration? And was this investment in Ebola R&D from entirely new funding, or was it diverted from other neglected diseases? Declining public funding One of the key findings of the 2015 G-FINDER report was that public funding for non-Ebola neglected disease R&D in 2014 fell to its lowest level since 2007. In this case, the US government again, unfortunately, led the way: US government year-over-year investment in non-Ebola neglected disease R&D fell by just over 2 percent in 2014, following even larger sequester-related cuts the previous year, to be nearly a quarter of a billion dollars lower than its peak in 2009. Public funding from other countries has remained steady, but ongoing cuts from the United States, the world’s biggest funder of neglected disease R&D, are cause for concern. Increasing industry investment In contrast to the decline in public funding, industry investment in neglected disease R&D reached its highest level in the history of the G-FINDER survey. Importantly, this reflected not only the sector’s Ebola R&D activity, but also significantly increased investment in R&D for malaria drugs and vaccines and HIV and AIDS vaccine research. More concerning was the fact that industry funding for TB fell for the fourth year in a row (down $10m or 8.7 percent)—an alarming trend, given the need for new vaccines, drugs, and diagnostics to combat the increasing threat of multidrug-resistant TB and extensively drug-resistant TB. Solidifying funding for PDPs In positive news, funding for product development partnerships (PDPs) rose for the second year in a row, driven by increased funding from the Bill & Melinda Gates Foundation. PDPs are instrumental in the development of new tools to fight neglected diseases, and are involved in the development of 40 percent of products in the neglected disease pipeline, despite accounting for just 16 percent of global funding in neglected disease R&D. The system failures in the global response to the Ebola outbreak have been well documented over the past months. But there should also be recognition of the successes and surprising rapidity with which R&D investment was mobilized. If we could translate this political and financial commitment to other neglected diseases, the impact would be huge. Reference: Moon S, Sridhar D, Pate MA, Jha AK, Clinton C, Delaunay S, et al. Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola. The Lancet. 2015 Dec 4;386(10009):2204–21.