Lead Author: John Reeder
Additional Authors: Robert Fraser Terry and Ryoko Miyazaki-Krause
Organization: The Special Programme for Research and Training in Tropical Disease (TDR)
Research and development (R&D) for health products normally focuses on diseases with a commercial market in high-income countries. R&D is still limited for diseases of poverty. Considering this, the Director-General of the World Health Organization (WHO) through the decision by the 2014 World Health Assembly, requested the Special Programme for Research and Training in Tropical Diseases (TDR) to investigate potential mechanisms and tools to finance R&D to accelerate product development. The TDR report, Health Product R&D Fund: a proposal for financing and operation, to be published on 17 March 2016, describes how a potential pooled fund would operate under the governance of the WHO Member States, and how the tools, some of which will be published later in 2016, could be used for transparent and efficient operation of the proposed framework. The tools described in the Report include:
- The Portfolio-to-Impact model: a new robust financial modelling tool which allows estimating minimum funding scenarios;
- A compendium of Target Product Profiles: a new online resource that would be housed in WHO which collects and maps health product pipelines in a standardized manner;
- Operational mechanisms for efficient and transparent management of the fund as well as the portfolio of health product R&D projects.
The development of a new R&D fund under WHO would create, for the first time, a mechanism to identify and cost out health products for diseases of poverty. The fund would ensure that any products that are developed would be affordable, accessible, acceptable and available to the countries that need them.
TDR is confident that its existing governance mechanisms could establish a transparent and efficient mechanism to manage a proposed fund and portfolio. Disease-endemic and donor countries would form part of this governance structure, opening the door to new funders.
Research and development (R&D) for health products normally focuses on diseases with a commercial market in high-income countries. R&D is still limited for diseases of poverty. Considering the lack of appropriate and affordable health products, such as diagnostics, vaccines and treatments, for the diseases primarily affecting developing countries, in 2003, the WHO Member States agreed (1) to conduct a special investigation to “collect data and proposals from the different actors involved and produce an analysis of intellectual property rights, innovation, and public health, including the question of appropriate funding and incentive mechanisms for the creation of new medicines and other products against diseases that disproportionately affect developing countries.” This investigation resulted in the Report of the Commission on Intellectual Property, Innovation and Public Health (CIPIH Report (2)) published in 2006. In response to the CIPIH Report, the Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG (3)) was established and developed the Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPA-PHI (4)), which was adopted at the WHA in 2008.
To further examine financing and coordination of R&D, as well as proposals for new and innovative sources of funding to stimulate R&D related to diseases affecting developing countries, the Expert Working Group on R&D: Coordination and Financing (EWG (5)) was established in November 2008. The report prepared by the EWG was considered insufficient primarily by developing country member states and the Consultative Expert Working Group on R&D: Financing and Coordination (CEWG (6)) was established in 2010 to “examine current financing and coordination of R&D, as well as proposals for new and innovative sources of financing to stimulate R&D related to Type II and Type III diseases and the specific research needs of developing countries in relation to Type I diseases.”
WHO conducted a review of current organizations and structures that would be best suited to house a potential new R&D Fund, and identified TDR to consult. At the 2014 WHA (7), Member States requested the Director-General to investigate potential mechanisms and tools to finance R&D to accelerate product development for diseases primarily targeting low- and middle-income countries (LMICs).
TDR was asked to conduct this work, the results of which will be published on 17 March 2016, in a new report: Health Product R&D Fund: a proposal for financing and operation. This report outlines the outcomes of the preparatory studies conducted to explore financing mechanisms, including options for the fund’s creation and key operational considerations. The report describes how a potential pooled fund would operate under the governance of the Member States of the WHO, and how the tools, some of which will be published later in 2016, could be used for transparent and efficient operation of the proposed framework.
This proposed global financial mechanism is unique from other R&D financing initiatives that are more regionally focused and centered on capacity building. Interest is already demonstrated by financial contributions provided by Brazil, India and South Africa to support CEWG’s demonstration projects (8).
With regard to the four main criteria of the High Level Panel, this report has considered the following.
Impact on policy incoherence:
Despite the funding of over US$ 3.4 billion reported by the 2015 G-Finder to support research and development (R&D) for diseases of poverty, over 1.4 billion people, including 500 million children, continue to be affected by those diseases annually due to lack of new diagnostics, vaccines and treatments that are affordable, accessible, acceptable and available. The current lack of global policies as well as mechanisms to identify and prioritize health R&D needs hinders development of robust long-term R&D strategies which could also assist in preparing for emerging diseases. The report offers potential mechanisms to increase policy coherence by having a transparent and readily available map on diseases of poverty, and to accelerate product development by facilitating coordination among global public health stakeholders. It also describes how a global forum could be established to gather major funders and relevant stakeholders to share their objectives and to discuss potential coordination and collaboration in product development efforts for diseases of poverty. The involvement of all WHO Member States in the governance mechanism ensures transparency and further encourages coherent policy development both at the global and national level.
Impact on public health:
The proposed mechanisms with a sufficient fund would greatly accelerate development of quality diagnostics, vaccines and treatments under the overarching principles of end products being affordable, accessible, acceptable and available to over 1.4 billion people, including 500 million children, from LMICs which are affected by these diseases annually.
Impact on human rights:
As stated in the constitution of the WHO, the right to health is defined as “the enjoyment of the highest attainable standard of health”. It is the first international demarcation of human rights to health and the report’s proposed mechanism, if implemented, would assist in developing quality diagnostics, vaccines and treatments that are needed to bring all people to achieve “the highest attainable standard of health”. This also supports achievement of SDG 3 principle to “ensure healthy lives and promote well-being for all”. The proposed mechanism is flexible and not limited to communicable diseases, but applicable to noncommunicable diseases that are increasingly affecting developing countries. Access to affordable medicines is a central pillar of achieving universal health coverage and the main objective for this proposal.
The proposal is to establish a new global R&D fund under the WHO structure which is managed by TDR. WHO will set global priorities through its Prioritization Mechanism based on data collected by the new WHO Global Observatory on Health R&D.
At a special meeting in May 2016, WHO Member States will consider the following recommendations proposed in the Report prior to decision-making at the Sixty-ninth World Health Assembly:
1. A fund of sufficient scale (e.g. incremental increase starting at US$ 10–15 million up to US$ 100 million disbursed annually over a 10-year period) should be set up to support health product R&D;
2. The fund’s portfolio of projects (e.g. gradual increase in number of funded projects starting from 5–7 projects per year to an average of 35–40 projects) should be balanced between short-term repurposing and longer term discovery efforts;
3. The fund should have transparent, objective and non-political evidence-based decision-making processes; and
4. The fund should be able to accept “new” funders and maximize leverage by encouraging new partnerships and collaborations.
Subject to approval of the Member States and the availability of new funding, TDR is confident that, if requested, it could establish a transparent and efficient governance mechanism to manage the pooled fund and to assist in accelerating the development of diagnostics, vaccines and treatments for diseases of poverty. The work presented in this report is not disease specific and offers new thinking about how these challenges might be met.
Although we recognize that new financing is being called to meet various health challenges, such as antimicrobial resistance, preparation for potential pandemic outbreaks and the persistent issues related to diseases of poverty, all share a common characteristic of being underserved by the commercially-driven R&D model. Therefore, public finance is needed to leverage funds to accelerate product development and establishment of coherent policies is needed to provide incentives to ensure end products are affordable, accessible, acceptable and available to ensure healthy lives and promote well-being of everyone in the world.
The report is structured in four sections. First, it summarizes the current R&D landscape for Type III and II diseases. (9) Then, it presents options for setting up a R&D financing mechanism. It also provides guidance on how to operate this mechanism, including setting up the SWG. Finally, it reviews the set of tools that would assist the SWG in decision-making and portfolio management. Even though developing countries’ special R&D needs for Type I diseases was not investigated, the Financial Mechanism presented in this report would still be applicable as this broadly falls under the need to repurpose existing health products.
Research and development (R&D) for health products normally focuses on diseases with a commercial market in high-income countries. R&D is still limited for several of the following diseases as defined by the World Health Organization (WHO):
• Type I diseases: occur in both rich and poor countries with large numbers of vulnerable populations in each;
• Type II diseases: occur in both rich and poor countries, but with a substantial proportion of the cases in poor countries;
• Type III diseases: found overwhelmingly or exclusively in developing countries. (10)
There are funding bottlenecks for R&D throughout the development pipeline for Type III and II diseases, in particular with respect to translational research and expensive phase III clinical trials. R&D financing needs differ by disease, with diagnostics most critical for some diseases and new therapeutics or vaccines for others. WHO is currently developing a broad Prioritization Mechanism to set priorities based on data collected by the WHO Global Observatory on Health Research and Development (R&D). It should be noted that the exact structure and mandate of the Prioritization Mechanism had not been defined during the preparation of report. However, the financing and downstream coordination mechanism described in this report will be applicable to putting into operation any priorities set by the Prioritization Mechanism. Financing and coordination mechanisms would help to address some of the most critical funding bottlenecks and shortages. These mechanisms could perform three main roles.
1. An operational priority-setting mechanism could unite diverse stakeholders to effectively focus on the most critical unmet needs in the R&D of health products, as identified by the WHO Prioritization Mechanism.
2. An active coordinating mechanism could include the creation of a new forum to convene donors, making global R&D activities and funding needs more transparent. Larger donors are unlikely to relinquish control of their independent funding decisions, making formal coordination challenging. However, such a forum could ensure identification of critical R&D gaps and agree on how those areas could be funded, by providing a formal mechanism for discussion, establishing collaborations among funders and providing a “base” level of funding for projects that could benefit from other funders becoming involved.
3. A direct fund could help address some of the most critical R&D financing needs for Type III and II diseases. The potential of various fund sizes to launch new health products by 2030 was investigated. The results indicate that, in the long run, an annual disbursement of US$ 100 million or more would have the possibility of funding a portfolio of the most promising and innovative product development projects, which could overcome some of the larger gaps (instead of focusing solely on relatively low-cost activities such as drug reformulation or repurposing). The fund could also address the financing needs outlined below.
(a) It should be constituted with “new” money, as opposed to redistributing money that is already available to public health researchers and developers.
(b) The convening power of WHO could help to access such new funds, but care would have to be taken to ensure efficient and transparent processes.
(c) Building on experience acquired from product development partnerships (PDPs), public-private R&D initiatives, other funds and the private sector, the fund should have a diversified portfolio of projects and enable targeted partnerships along the projects’ development paths. The portfolio should include projects that could provide shorter term projects (development of repurposed drugs or improved point-of-care diagnostics using existing platforms) as well as longer term discovery efforts.
It will be critical to provide a setup and process that enables transparent, objective and non-political decision-making. To ensure this, a Scientific Working Group (SWG) would be convened and managed by TDR, as per its usual operating framework governed by three bodies: the Joint Coordinating Board (JCB), the Standing Committee, and the Scientific and Technical Advisory Committee (STAC). The SWG would be responsible for: the management of the health product projects portfolio, including detailed analyses of the R&D landscape; the identification of project types with high feasibility and impact potential; the development of calls for proposals; the monitoring and evaluation of projects; and the financing recommendations of selected projects.
Together with a world-class knowledge of infectious diseases, SWG members should have experience in:
• leading product development;
• assessing risks;
• making challenging portfolio decisions, from feasibility evaluation of chemistry, manufacturing and controls (CMC) (11) to clinical trials;
• evaluating regulatory compliance and providing regulatory guidance;
• working in health systems in low- and middle- income countries (LMICs);
• financing or developing businesses, including being able to assess projects’ potential to deliver health impacts and their probability of success, and assess teams’ capacities and experience;
• evaluating potential health and economic impact.
This core SWG could be supplemented by expert groups, such as legal and intellectual property (IP) experts, health economists, and disease and product specialists from the individual priority disease areas set by the WHO Prioritization Mechanism. Depending on the status of a funded project, the SWG would consider endorsing the use of specific incentive mechanisms (such as grant-funded push mechanisms), or proposing purchase commitment pull mechanisms to the WHA through the JCB. The ideal SWG operational mechanism would depend on how priorities are set by the WHO Prioritization Mechanism but the SWG could decide in real-time how to prioritize and put into operation the different types of projects. Depending on the availability and/or suitability of target product profiles (TPPs), the SWG would establish or finalize TPPs or candidate product profiles.
The SWG would also identify and clarify milestone goals before projects are funded, and ensure they are met. The SWG’s decision-making on the portfolio could be assisted by using toolkits, such as a compendium of TPPs and a framework for prioritizing projects or guiding investment decisions.
Key recommendations presented above will be considered by the WHO Member States during the special meeting in May 2016.
The High Level Panel may wish to consider how the recommendations outlined in this report could find wider adoption and assistance in filling the R&D pipeline gaps for diseases of poverty or to fulfill other unmet needs.
Bibliography and References
Health Product R&D Fund: a proposal for financing and operation, Special Programme for Research and Training in Tropical Diseases (TDR). To be published on 17 March 2016 and made available at http://www.who.int/tdr/capacity/gap_analysis/en.
(1) WHA56.27: http://apps.who.int/gb/archive/pdf_files/WHA56/ea56r27.pdf
(2) CIPIH: http://www.who.int/intellectualproperty/en/
(3) IGWG: http://www.who.int/phi/igwg/en/
(4) GSPA-PHI: http://www.who.int/phi/publications/gspa-phi/en/
(5) EWG: http://www.who.int/phi/ewg/en/
(6) CEWG: http://www.who.int/phi/cewg/en/
(7) WHA decision 67(15): http://apps.who.int/gb/ebwha/pdf_files/WHA67-REC1/A67_2014_REC1-en.pdf#page=81
(8) WHO CEWG demonstration projects: http://www.who.int/phi/implementation/phi_cewg_meeting/en/, accessed 26 January 2016.
(9) Due to time constraints, the focus of this report is on Type III and II diseases.
(10) http://www.who.int/phi/3-background_cewg_agenda_item5_disease_types_final.pdf, accessed 26 January 2016.
(11) The importance of evaluating the quality of chemical starting points was underscored by the experts involved in the Global Health Innovative Technology (GHIT) Fund in their recent publication: Katsuno K. et al. Hit and lead criteria in drug discovery for infectious diseases of the developing world. Nat Rev Drug Discov. 2015;14:751–8). Although this report covers the investigations from preclinical to phase III studies, further investigations may be required to investigate cost, time and attrition rates required in early-stage research and discovery phase, including hit discovery, target validation, assay development, lead generation and lead optimization.
Other material related to this topic. The WHO/TDR technical report series on research:
Research priorities for helminth infections: http://www.who.int/entity/tdr/publications/helminth_infections/en/index.html
Research priorities for zoonoses and marginalized infections: http://www.who.int/entity/tdr/publications/zoonoses/en/index.html
Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis: http://www.who.int/entity/tdr/publications/research_priorities/en/index.html
Research priorities for the environment, agriculture and infectious diseases of poverty: http://www.who.int/entity/tdr/publications/environment/en/index.html
Research priorities for tuberculosis research: http://www.who.int/entity/tdr/publications/tuberculosis_research/en/index.html