Breakthroughs Blog: WHO

The 140th session of the World Health Organization (WHO) Executive Board (EB) is officially done and dusted. Despite one of the lengthiest agendas in the history of the EB, the meeting actually finished a day early on January 31. As GHTC noted before the meeting, there were several agenda items relevant to global health research and development (R&D), in addition to broader decisions about WHO’s overall future direction. Some resulted in substantive decisions, while others served as an opportunity for delegates to provide input to shape resolutions for the World Health Assembly (WHA) in May. Here are the highlights from the week: Director-General Elections – Decision Point The biggest news out of the EB was the narrowing of the pool of Director-General (DG) candidates from six to three in preparation for a vote at WHA. Contrary to expectations heading into the EB vote, Dr. Sania Nishtar (Pakistan), Dr. Tedros Ghebreyesus (Ethiopia), and Dr. David Nabarro (UK) made the shortlist, while Drs. Flavia Bustreo (Italy) and Philippe Douste-Blazy (France), both of whom many considered to be strong contenders going into the meeting, failed to make the cut. The three have all positioned themselves as reform candidates, committed to continuing many of the reform processes started under outgoing DG Margaret Chan. The campaign now kicks into high gear, and it will be interesting to see if and how the candidates evolve their platforms to respond to priorities from the full membership of WHO now that they have made the shortlist. Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property – Decision Point The EB approved a new terms of reference for the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPOA), recognizing the need for WHO to consult with private-sector companies and establishing rules for this engagement as set out by the Framework for Engagement with non-State Actors (FENSA). Adopted in 2008, the GSPOA guides WHO’s work on fostering innovation and improving access to medical technologies for people in low- and middle-income countries. It was designed to promote innovation, build capacity, and mobilize resources by positioning WHO in a central and strategic role managing the relationship between public health, innovation, and intellectual property. As it nears its decade anniversary, WHO is undertaking a review of progress, as well as identifying areas for reform moving forward. In line with WHO’s move to put in place more stringent conflict of interest protections, initial drafts of the terms of reference for the review would have limited the agency’s ability to engage with private-sector companies involved in health R&D. The final draft as approved, however, recognizes the need to consult with these groups. Follow up to the Consultative Expert Working Group on R&D: Financing and Coordination and the UN Secretary-General’s High-Level Panel on Access to Medicines – Input/Information Point The EB’s session to review progress on the establishment of an R&D observatory and pooled fund at WHO to finance R&D as recommended by the Consultative Expert Working Group on R&D: Financing and Coordination (CEWG) was largely sidelined by member state debate on how or whether to carry forward recommendations of the United Nations (UN) Secretary-General’s High-Level Panel on Access to Medicines (HLP), which has proved highly controversial among member state delegations. In the run-up to the meeting, the officers of the EB decided not to include a separate item for discussion of the HLP’s findings in the EB agenda. As a compromise, the president of the EB permitted discussion of the HLP findings to occur under the existing CEWG agenda point. A number of countries, including Brazil, India, Iran, and others had strenuously objected to the exclusion of a HLP agenda item, arguing that WHO is relinquishing its global leadership role on a topic fundamental to health in not taking the lead on implementation of the HLP recommendations. Others, including the United States and some European delegations including Switzerland, Germany, and the UK argued that there was no consensus on the panel’s findings, that the report unfairly targeted specific countries, and that the HLP process had been overly narrow from the start in focusing on intellectual property, as opposed to a broader set of factors that impact access. The EB also did review progress on implementation of the CEWG recommendations. The final plan to establish an R&D observatory will be up for approval at this year’s WHA, while the proposal for a pooled fund to compliment the observatory is significantly less advanced, and work is still underway to determine exactly how a fundraising mechanism can be constructed to support it. GHTC delivered a statement at the meeting welcoming progress by WHO on the CEWG process and encouraging full funding of the observatory and ongoing consultation with stakeholders as the process moves forward. Antimicrobial Resistance – Input/Information Point Following on the heels of last year’s political declaration of the high-level meeting of the UN General Assembly on antimicrobial resistance (AMR), the EB reviewed progress made by WHO and other UN technical agencies to establish a plan to operationalize the declaration’s key recommendations, including spurring R&D for new antibiotics and other tools to combat AMR. As GHTC noted in our statement delivered at the EB, the effectiveness of follow up mechanisms to hold stakeholders accountable for their commitments on AMR will be critical to the overall success of the fight. Many delegates’ interventions focused on this need to deliver on commitments, and the tone of the session seemed to indicate that we will see a robust plan approved at WHA, which will be a great win for global health. R&D for Potentially Epidemic Diseases – Input/Information Point The EB reviewed progress by WHO on establishing an R&D blueprint for potentially epidemic diseases to reduce the delay between the identification of an outbreak and the deployment of effective medical interventions, calling for the agency to accelerate its work, given that the next outbreak can happen at any time. GHTC highlighted in its statement the importance of the blueprint addressing platform technologies, frameworks for collaborative R&D, and investing in regulatory/procurement systems strengthening. These efforts by WHO are part of its self-examination following lessons learned in the response to the Ebola outbreak. Heading into WHA in May, the agenda will be very full. In addition to the items above, the Assembly will also consider WHO’s response in crisis situations, polio elimination, immunization, WHO’s overall budget, implementation of the International Health Regulations to enhance global health security, global shortages of medicines and vaccines, and dozens of other items. GHTC will continue monitoring and will provide updates before, during, and after WHA.

A researcher holds onchocerciasis (river blindness) diagnostic tests. Photo: PATH/Patrick McKernLast Thursday, the World Health Organization (WHO) took the first step toward establishing an essential diagnostics list (EDL), releasing a proposal outlining how it intends to develop and operationalize the list by early 2019. This move follows calls by GHTC and other partners for the agency to establish an EDL to provide guidance to countries on the vital diagnostics that should be made available through health systems to complement WHO’s existing Model List of Essential Medicines (EML).As GHTC has previously noted, the need for an EDL to complement the EML is clear and has been compellingly demonstrated. An essential diagnostics list would not only help health care providers, particularly in low- and middle-income countries, improve diagnostic capacity and access, and thus improve patient care, it also holds potential to catalyze research and development (R&D) for new diagnostics by exposing health areas where we today lack appropriate and effective tools. GHTC is pleased to see WHO heed this call from advocates and scientists and begin the process to establish an EDL.A researcher holds onchocerciasis (river blindness) diagnostic tests. Photo: PATH/Patrick McKernThe proposal released by WHO lays out the broad principles the agency will follow in standing up an initial version of the diagnostics list. This includes: Focusing on in vitro diagnostics (IVDs): Given the large number of diagnostic tools, WHO believes that it will be most feasible to focus the first version of the list on IVDs—which are tests on samples derived from the human body—before considering expanding the list at a later date to include other diagnostic methods like radiological tests or x-rays. Targeting the list to support and complement the existing EML: Even limiting the list to IVDs leaves a wide breadth of potential diagnostics to be considered. Therefore, WHO proposes to start with identifying the diagnostics needed to enable appropriate use of medicines on the EML. Making an allowance for IVDs to address outbreak identification and response: While the EDL would be designed initially to complement medicines on the EML, WHO acknowledges that there is a clear need to help countries identify diagnostics necessary to address disease outbreaks with pandemic potential. As such, the EDL could include initially or be expanded later to include these technologies as well. Including diagnostics for various levels of the health care system: Different levels of health care facilities have different capacities and diagnostic needs within clinical care. Therefore, WHO will ensure the EDL includes diagnostics to meet the needs of these different providers and contexts. Designing for ease of use: WHO will focus on presenting the EDL in a format that is easy-to-use and accessible for countries, to facilitate use of the information and uptake of the suggested technologies. WHO is considering a variety of methods to support this goal.  Moving forward, WHO’s essential medicines staff will consult with the Expert Committee on the Selection and Use of Essential Medicines at its meeting in March to gather technical input on how to best operationalize the principles outlined above. Based on this feedback, a pilot group of diagnostics will be evaluated based on existing evidence of programmatic impact, with the goal of completing the development of an initial version of the EDL by early 2019.GHTC will continue to follow this issue closely and work with our members to ensure that the first version of the EDL is solidly grounded in our decades of combined experience with diagnostics and that the process of establishing the list moves forward efficiently. Keep watching this space for updates.

2016 was a year that ushered in significant shifts in the global health landscape. We witnessed the waning of the Ebola epidemic and the waxing of the Zika outbreak; important leadership changes among the biggest institutional players in global health; and the development and introduction of new innovations that could turn the tide against leading infectious disease killers. As the year comes to an end, GHTC is reflecting on the top stories in global health innovation that made news in 2016. Here are seven of those top moments: 1. Scientists mobilize against Zika A vial of the National Institute of Allergy and Infectious Diseases (NIAID) Zika Virus Investigational DNA Vaccine (Photo: NIAID).Once considered an obscure virus responsible for a mild illness, Zika took the world by storm in 2016. As the virus gained a foothold in more than 60 countries, its association with devastating birth defects and neurological conditions was firmly established. Prior to Zika’s emergence in the Americas, only 25 research papers had been published on the virus. As the epidemic grew, scientists around the world joined the fight against Zika, often sharing their data and research in real time to speed progress. Thanks to the efforts of these researchers, over the past year our scientific understanding of Zika has grown exponentially, and we have advanced a robust pipeline of new tools to prevent, detect, and treat Zika. Today, there are more than 35 Zika vaccine candidates under development; 13 Zika diagnostics have been authorized for use by the US Food and Drug Administration; and researchers are screening novel compounds and evaluating existing drugs to advance treatments for the disease. 2. The world commits to the fight against antimicrobial resistance United Nations General Assembly (Photo: GHTC/Matthew Robinson). 2016 marked the year the world finally got serious about tackling antimicrobial resistance. On the heels of several major analyses examining the potentially devastating health and economic impact of antimicrobial resistance, the United Nations (UN) General Assembly convened global leaders for a high-level summit on antimicrobial resistance—the fourth time such a meeting has been held on a health-related topic during the UN’s 71-year history. At the close of the summit, UN member states unanimously endorsed and adopted a political declaration committing to developing action plans and policies; mobilizing resources; and supporting public awareness, surveillance, and R&D efforts to combat antimicrobial resistance. It is our hope that 2017 will mark the year political commitment translates to concrete action to advance the development of new antibiotics. 3. New strategies deployed to stymie mosquito-borne diseases Mosquito-borne diseases remain an age-old scourge, but 2016 saw the advancement of several novel strategies to combat these tiny foes. Efforts to combat mosquito-borne diseases with the transmission blocking–bacteria Wolbachia took an important leap forward this year. Past studies have shown that when the Wolbachia bacteria is introduced to Aedes aegypti mosquitos—which carry viruses like Zika and yellow fever—it prevents the viruses from replicating and blocks further transmission. Because the bacteria can be passed from one generation of mosquitoes to the next, the bacteria offers hope for eliminating a virus’s presence within a local mosquito population. After several years of conducting small-scale tests of this method, the Eliminate Dengue Program announced in 2016 it would begin conducting two large-scale trials in South America to determine whether this approach is effective in halting the spread of mosquito-borne diseases in large urban settings. This year the biotech company Oxitec also advanced efforts to test the use of genetically modified mosquitoes to reduce mosquito populations and disease transmission. The company has engineered mosquitoes that mate with A. aegypti mosquitoes, producing offspring that are unable to mature to adulthood. Early last year, Oxitec introduced the mosquitoes into the Brazilian city of Piracicaba, resulting in an 82 percent decrease in the population of A. aegypti mosquitoes in just nine months. Now, Oxitec has expanded the trial to a larger geographical area and is also initiating trials in the Florida Keys and the Cayman Islands. 4. World’s first kid-friendly TB medicine launches Children who receive tuberculosis (TB) medicines require a different dose than adults, yet until this year, there were no TB medicines designed specifically for children, so parents were forced to split or crush adult pills in an attempt to administer the right dose to their child. This year, that all changed with the launch of the world’s first kid-friendly TB medication. Developed by TB Alliance, the medicine is designed with the unique needs of children in mind: It is fruit-flavored, dissolvable in water, easy to administer, and appropriately-dosed. Already, more than 30 countries have adopted the new medicines, and enough orders have been placed to treat half of childhood TB cases worldwide. 5. Unique HIV prevention option for women reaches important development milestone Image captionMonthly vaginal dapivirine ring helps protect women against HIV (Photo: International Partnership for Microbicides). Women may soon have a powerful new tool at their disposal to prevent HIV infection. Earlier this year, the International Partnership for Microbicides (IPM) announced the results of two large phase 3 clinical trials demonstrating that a monthly vaginal ring containing the antiretroviral drug dapivirine can help protect women from HIV. While initial results indicated that the dapivirine ring reduced HIV risk by approximately 30 percent, further analysis revealed that the ring reduced infection rates by 75 percent in women who used the ring consistently. Now, IPM is seeking regulatory approval for the dapivirine ring and is conducting open-label studies, enabling trial participants to continue using the ring as IPM collects additional data. The dapivirine ring is the only long-acting, female-initiated HIV prevention tool to have proven successful in phase 3 clinical trials. Young women in sub-Saharan Africa are more than twice as likely to be infected with HIV than their male counterparts, and thus female-centered prevention tools are needed stem the epidemic. 6. Roll out begins of world’s first malaria vaccine candidate After decades of development and testing, the world’s first malaria vaccine candidate will soon be introduced in several communities in sub-Saharan Africa. The vaccine—RTS,S—was developed by PATH and GlaxoSmithKline and received a positive opinion from the European Medicines Agency last year following completion of phase 3 clinical trials. In November, the World Health Organization (WHO) announced it would pilot and evaluate the vaccine in real-life settings, thanks to funding from The Global Fund; UNITAID; and Gavi, the Vaccine Alliance. Pending results of these pilot tests, WHO will determine whether to deploy the vaccine on a wider scale. 7. New global health technologies advance through the pipeline PATH launches an easy-to-use, rapid diagnostic for onchocerciasis (Photo: PATH/Dunia Faulx) Over the past year, several other promising new health innovations have moved through the development pipeline and one step closer to reaching the hands of patients: Two important health tools—a novel, affordable oral cholera vaccine developed by the International Vaccine Institute, and the Woman’s Condom developed by PATH and partners—received WHO prequalification this year, paving the way for their procurement by UN agencies and other international procurement organizations. Two new rapid diagnostic tests for the neglected tropical diseases onchocerciasis (river blindness) and lymphatic filariasis were launched this year. Developed by PATH, these tests provide results in just 30 minutes and can be stored at a wide range of temperatures. Development has begun for an affordable therapy for hepatitis C. In 2013, the world’s first cures for hepatitis C hit the US market, however, treatment remains out of reach for many patients due to the high price tag. This year, the Drugs for Neglected Diseases initiative announced it would begin testing an alternative therapy in phase 2 and 3 clinical trials, with a guarantee from the manufacturer that, if successful, the entire regimen will be sold for no more than US$294.  As 2016 draws to a close and 2017 begins, it is time for the global health community to redouble our efforts to make sure this vital progress in global health innovation continues to ensure that people around the world will have access to lifesaving and life-improving health technologies.

Researchers examine onchocerciasis (river blindness) diagnostic tests. PATH/Patrick McKernWithout the right diagnostics, we can’t effectively treat diseases. It’s an obvious statement. But in many low- and middle-income countries, doctors and health care workers don’t have access to the diagnostic tools they need, often because existing tests are too costly and not appropriate for low-resource settings or tests don’t exist at all. Without the right tests, doctors end up relying on patient symptoms, which can be remarkably similar across different diseases. The result can be devastating: A wrong diagnosis can lead to the wrong treatment or a failure to recognize the presence of disease with pandemic potential. This problem is a common one: in half of African countries, more than 80 percent of those treated for malaria receive medicine without confirmation of a diagnostics, and during the 2014–2015 Ebola outbreak, efforts to contain the outbreak were hampered by a lack of rapid, point-of-care tests that could be deployed easily in the field.In a recent New England Journal of Medicine article, a group of scientists and doctors suggested an innovative idea to improve global access to critically-needed diagnostic tools: create a list.More specifically, they’re calling for the creation of an essential diagnostics list to complement the World Health Organization’s (WHO) Model List of Essential Medicines (EML). The EML provides guidance to countries on what drugs, therapies, and treatments should be made available to citizens to meet basic public health needs. Likewise, an essential diagnostics list would provide guidance on the vital diagnostics tests that should be available in each country, depending on its disease burden. In this way, the two lists would support and complement each other, with the diagnostics list identifying the tests needed to enable appropriate use of medicines on the EML.The transformative potential of an essential diagnostics listThe authors of the article have detailed the many ways an essential diagnostics list could be a transformative force for improving diagnostic capacity and access. By setting global guidance on the diagnostics tests recommended to countries to address basic health needs, an essential diagnostics list could provide a forceful policy argument for governments to invest in making existing diagnostics more broadly available. A list could also encourage governments to make further improvements to health systems to support diagnostic use, including laboratory training programs and strengthening health infrastructure and supply chains.But what GHTC is most excited about is one of the lesser-discussed aspects of an essential diagnostics list: its potential to catalyze research and development (R&D) of new diagnostic tools. A patient gets tested for malaria. PATH/Gena Morgan Diagnostic R&D is a significantly underfunded area of research, accounting for less than 5 percent of global funding of neglected disease R&D. The result is a lack of diagnostic tools targeting the specific health needs of low- and middle-income countries, such as easy-to-use platform technologies or rapid, point-of-care tests that can be used in remote, rural clinics.By detailing which diagnostics are necessary to support health interventions on the EML, an essential diagnostics list would readily expose health areas where we today lack appropriate and effective tools. In this way, the list could signal to product developers, industry, and donors where funding and attention is needed to facilitate diagnostic R&D.The impact of improved diagnostic access and capacity would be considerable: better care and treatment for patients, reduction in the inappropriate use of medicines which is contributing to drug resistance, and improved ability to detect emerging diseases like Zika and Ebola early before they become epidemics.Joining the call for an essential diagnostics listOn Wednesday, GHTC sent a letter, signed by 11 of our member organizations, to WHO’s assistant director-general for Health Systems and Innovation calling for WHO to spearhead the creation of an essential diagnostics list. Given WHO’s experience in administering the EML and its ongoing work in providing guidance on diagnostic testing and laboratory accreditation; we believe the organization is uniquely positioned to lead on the development and implementation of this list. But making this initiative a reality will require the support of civil society and member states, as well as additional funding to stand-up the program at WHO.It is clear that treatment can be improved with essential diagnostics—ones we have today and others yet to be developed. We urge WHO and its member states to heed this call to establish an essential diagnostics list. It’s a smart, cost-effective idea that could advance diagnostic R&D and access.Update: On November 18, Dr. Marie-Paule Kieny, WHO Assistant Director-General for Health Systems and Innovation, replied to GHTC's letter indicating that WHO is pursuing analysis of the idea and outlining next steps. GHTC will continue to monitor progress and engage with WHO in support of this initiative.