Outbreaks of emerging infectious diseases in the 21st century, from the emergence of severe acute respiratory syndrome (SARS) in 2003 to the recent reemergence of Ebola virus disease, continue to demonstrate that the international community does not have adequate systems in place to reliably prepare for, detect, and rapidly respond to large-scale public health emergencies. Countless lives have been lost, and billions of dollars have been spent responding to and recovering from these outbreaks. What and where will the next outbreak, pandemic, or epidemic be; how far will it spread and how quickly; and how much human and economic loss will be sustained before it is brought under control? The time is now, said Victor Dzau, President of the U.S. National Academy of Medicine (NAM), in his opening remarks, before the next outbreak, to define and implement an effective global architecture for recognizing and mitigating the threat of epidemic infectious diseases.
1 The planning committee’s role was limited to planning the workshop. This workshop summary has been prepared by the rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not necessarily endorsed or verified by the National Academies of Sciences, Engineering, and Medicine, and should not be construed as reflecting any group consensus.
Since the 2014 Ebola outbreak many public- and private-sector leaders have seen a need for improved management of global public health emergencies. The effects of the Ebola epidemic go well beyond the three hardest-hit countries and beyond the health sector. Education, child protection, commerce, transportation, and human rights have all suffered. The consequences and lethality of Ebola have increased interest in coordinated global response to infectious threats, many of which could disrupt global health and commerce far more than the recent outbreak.
With encouragement and input from the World Bank; the World Health Organization (WHO); and the governments of the United Kingdom, United States, and West African countries; and support from various international and national organizations (Ford, Gates, Moore, Paul G. Allen Family, and Rockefeller Foundations; Dr. Ming Wai Lau; the U.S. Agency for International Development; and the Wellcome Trust), the NAM agreed to manage an international, independent, evidence-based, authoritative, multistakeholder expert Commission3 on improving international management and response to outbreaks. As part of this effort, the Institute of Medicine (IOM) convened four workshops in the summer of 2015 to inform the Commission report. These workshops examined questions of governance for global health, pandemic financing, resilient health systems, and research and development of medical products. Each workshop gathered diverse perspectives on a range of policies, operations, and options for collaboration to improve the global health system. A published summary from each of the workshops has been independently written and reviewed, and their release will be coordinated.4
The Workshop on Research and Development of Medical Products is one of the four workstream activities of the Global Health Risk Framework Initiative. An independent planning committee was charged with developing the workshop to consider strategies, systems, and policies needed to foster communication and create partnerships to advance the development
2 For more information see http://nam.edu/initiatives/global-health-risk-framework (accessed October 30, 2015).
3 For more information on the Commission see http://nam.edu/initiatives/global-health-risk-framework (accessed October 20, 2015).
4 Summaries from the other three workshops can be found at http://iom.nationalacademies.org/reports/2016/GHRF-Governance; http://iom.nationalacademies.org/reports/2016/GHRF-Finance; http://iom.nationalacademies.org/reports/2016/GHRF-Health-Systems.
of vaccines, diagnostics, therapeutics, and personal protective equipment (PPE) for emerging infectious diseases (see Box 1-1). The workshop was co-hosted by the IOM and The University of Hong Kong, in Hong Kong, on August 19-21, 2015. Invited experts and participants from academia, industry, U.S. and other government organizations, and civil society were welcomed by Victor Dzau and Gabriel Leung, Dean of the Li Ka Shing Faculty of Medicine at The University of Hong Kong. The workshop, co-chaired by Tachi Yamada, Managing Partner at Mountain Field, LLC, and
Statement of Task
An ad hoc committee will plan and conduct a 3-day public workshop that will provide a forum for relevant stakeholders to describe and provide input on the core needs and strategies to facilitate development of medical products to prevent, diagnose, treat, and protect from emerging threats such as global infectious diseases. The committee will define the specific workshop topics to be addressed, develop the agenda, select and invite speakers, and moderate workshop discussions.
The overarching objectives for the workshop include
- Gathering diverse perspectives of informed stakeholders to foster constructive discussion and facilitate the formation of collaborative solutions;
- Characterizing needs and gaps in current approaches to addressing global infectious disease outbreaks and other public health threats, and describing barriers to addressing those needs;
- Highlighting opportunities and potential approaches to improve the global system for addressing emerging threats;
- Documenting key successes and lessons learned from past global infectious disease outbreaks and other public health emergencies and how they may inform preparation and response to future outbreaks and emergencies; and
- Considering indicators and metrics that may be used to guide and assess the resilience of the global health infrastructure to future outbreaks and emergencies.
Speakers and workshop participants will be invited to describe and examine systems and approaches to discover and develop medical products to address emerging threats. The focus of the workshop will be on global systems and policy needs to foster communication, partnerships, and other strategies to advance medical product development. Workshop discussions will describe and examine the current state of approaches and infrastructure for research and development; barriers to the effective and efficient development of medical products; and potential strategies to address impediments to the research or development processes. The scope of medical products under consideration at the workshop will include
therapeutics, vaccines, diagnostics and other medical devices, and personal protective equipment. Key areas for consideration may include
- Product development: Describe current product development platforms; explore science and research needs, including needs for development of appropriate and effective regulatory science and evaluation tools.
- Clinical development: Discuss clinical trials approaches, including clinical trial methods and ethics considerations around enrollment and access to developing products in an emergency.
- Optimization for development: Explore incentives and infrastructure for product development, and conditions and needs for effective public–private partnerships and global/intergovernmental partnerships.
- Regulatory review standards and systems: Address regulatory considerations, including approaches to global regulatory harmonization and regulatory systems capacity.
- Manufacturing: Describe issues pertaining to supply chain management and product quality and integrity, and deployment of medical products.
- Legal issues: Highlight key legal considerations, including developer/manufacturer liability, distribution/sharing of biological samples, other patent/data exclusivity considerations, and sharing of preclinical and clinical trial data.
- Indicators: Explore indicators to facilitate and measure success and advances in the face of new and emerging threats.
Maria Freire, President and Executive Director of the Foundation for the National Institutes of Health (NIH), consisted of keynote lectures followed by panel discussions on the topics of models and incentives for engagement of product developers; discovery research; product development; regulatory review and approval; manufacturing and stockpiling; and supply chain and distribution. Participants then discussed top priorities and crosscutting themes from the discussions (see Appendix C for the full agenda). The following report summarizes the presentations from expert speakers and the discussions among workshop participants. Highlights and main points identified by individual participants during each major topic of discussion are summarized in a box at the start of each section.
In her keynote address to open the workshop, WHO Director-General Margaret Chan said that the world missed its first wakeup call, the 2009-2010 H1N1 influenza pandemic, perhaps because it was milder than expected. Ebola was thus a second wakeup call, she said, and she shared her perspective on the four pillars of the Global Health Risk Framework. (Highlights of Dr. Chan’s address are summarized in the box below.)
Highlights of WHO Director-General Chan’s Keynote Addressa
- Experience shows that, during a crisis, the traditional research and development model can be adapted, partnerships that are otherwise unlikely can be formed, and time frames can be compressed from years to months.
- The flexibility and collaboration that happens during a crisis needs to be moved upstream. Planning and agreement need to happen in advance of a crisis regarding rules of engagement, protocols and regulatory pathways, gaps in research and development, financing, liability, and other issues.
- A smarter approach is needed for funding and advancing research and development of medical products for emerging threats. Expecting the pharmaceutical industry to repeatedly redirect its research investments toward emerging crises with little to no return on investment is not a sustainable model.
- Coordination of efforts is essential. Affected countries are often inundated by partners and overwhelmed by multiple demands. When these partners cannot come together in a coordinated way, they are dissipating their collective energy. WHO has a range of mechanisms for fulfilling this coordination function.
- Governments must understand that if they do not pay attention to health and human security, their economic achievement could be eroded.
a This list is the rapporteurs’ summary of the main points made by Dr. Chan during her presentation and does not reflect any consensus among workshop participants.
A challenge when discussing governance in global health is who is governing whom. Global governance starts with national and subnational
governance, Chan said. In countries with highly decentralized political systems, the federal government often cannot get information from the state or provincial government. Every government should have a mechanism to ensure it can meet its responsibilities as a global citizen under the International Health Regulations (IHR), Chan said. She cautioned, however, that there often are disincentives for countries to report outbreaks quickly. Upon timely reporting, many have suffered rapidly instituted trade bans and travel bans (e.g., canceled flights and closed borders).
Health Systems Strengthening
With regard to health systems strengthening, Chan noted that many countries and states do not have any health system to start with. Although 194 countries have signed on to the IHR, only 64 countries actually have the core capacities to be able to implement them. Clinics and hospitals are lacking, doctors and nurses are few, and isolation wards are nonexistent. In Liberia, for example, there is one doctor per 100,000 population. Countries without the capacity to prevent, detect, notify, and respond need to be transparent and inform WHO, so that global assets can be brought to bear, Chan said. For example, during the Ebola outbreak, France, the United Kingdom, and the United States, mobilized military assets to build treatment centers to isolate people who were exposed. This was important, she explained, because people in that environment often cannot stay home for the 21-day isolation period (e.g., they do not have enough food for more than a few days). Quality of care is also important, Chan continued, and while many African leaders are prepared to invest in overall infrastructure, health clinics and hospitals are not considered infrastructure. The global conversation needs to include financing instruments for health infrastructure, including human resources and health information systems. Resilient health systems include both the public health elements as well as the primary health care elements. She suggested that one of the mistakes of the past was the approach of developing parallel systems (i.e., a system for HIV, another for malaria, and a separate system maternal and child health), which fragmented the government instead of bringing the systems together to provide quality care. Chan pointed out that 8.6 million people travel by air every day, with many more crossing borders on foot and by train, ship, or other means. In this highly connected world, mechanisms and systems are needed for early warning and national, as well as regional and global, response when required. The weakest links are the countries that have no capability.
Chan explained that WHO does not have funds set aside to respond; indeed, in an outbreak situation, WHO cannot mobilize funds without writing a proposal, appealing to governments, and waiting for them to give funds. In many cases, the donor imposes conditions (e.g., if the money given is to be used for immunization, WHO has no authority to use it for another area as needs change). It took almost 4 months before any funds were flowing in for the Ebola response, she said. To address this, WHO member states are discussing how to establish a contingency fund to support early stage mobilization so that WHO can respond before an outbreak gets out of control. The World Bank is also considering a pandemic financing mechanism.
Financing is needed not just for health system strengthening and crisis response, but also for research and development of medical products for emerging threats, Chan said. Every time there is a crisis, industry is asked to stop their normal research and production and make substantial investments with little or no expectation of a return. A mechanism must be developed in advance of the next crisis that establishes how to bring together the experts and identifies the financial and other resources that can be brought to bear for the research and development of diagnostics, vaccines, and therapeutics. Chan also noted that liability remains an unresolved issue for companies developing products for use in a crisis.
During the discussion, John Rex, Senior Vice President in Global Medicines Development at AstraZeneca, emphasized the importance of bringing the treasury, finance, and economics communities into the conversation. Chan agreed and pointed out that, in many governments, the Minister of Health might have no access to the Minister of Finance or the heads of state. Leaders must come to understand that if they do not pay attention to health and human security, their economic achievement could be eroded, she said. She noted that some presidents are beginning to realize that a health crisis of this nature cannot be handled by the health ministry alone.
Research and Development
Pharmaceutical companies decisively shape the global research and development agenda and, as private-sector entities, they invest primarily where profitable markets exist. The system inherently tends to neglect innovation for diseases that disproportionately affect poor populations. Although the need may be great, Chan said, the demand fails because of an inability of these people to pay (i.e., there is a market failure). WHO’s position is that no person should be denied access to lifesaving or health-promoting interventions for unfair reasons (including an inability to pay)
and, correspondingly, people should not suffer from diseases simply because market forces have failed to advance the development of vaccines or therapeutic options. Chan reminded the workshop participants of a 2006 independent commission report on intellectual property (IP) rights, innovation, and public health, which she said presented a wealth of evidence that the current system of pharmaceutical development is fundamentally flawed, leaving significant health needs unmet because of its reliance on patents and commercial incentives for priority setting and financing of medical research and development.5 A global strategy and plan of action to address the IP concerns raised was approved by consensus at the World Health Assembly in 2008. Countries now need new proposals for financing and coordinating needs-driven research and development. Chan acknowledged that the need to stimulate research and development for diseases impacting the poor differs from the need to ensure tools are available for new and emerging infections; however, they share more similarities than differences and there are the lessons from the past to draw from.
Since the emergence of the recent Ebola outbreak, WHO has been exercising its convening role and organizing a series of stakeholder meetings. Chan pointed out that chief executive officers (CEOs) of the large pharmaceutical companies have been openly sharing information on their research protocols, clinical trial designs, and production capacity. She challenged participants to move this flexibility and collaboration upstream, and find ways to plan and agree in advance to rules of engagement, define acceptable protocols and regulatory pathways, identify gaps in research and development for emerging pathogens, and identify opportunities for governments and foundations to promote this research and development. In this regard she urged participants to make use of WHO as a coordinating body to bring stakeholders together. Experience shows that the traditional research and development model can be adapted, partnerships that are otherwise unlikely can be formed, and time frames can be compressed from years to months.
During the discussion, Yamada highlighted the importance of having a “team captain” to deal with the multitude of issues that need to be coordinated. Chan agreed and noted that the three countries affected by the recent Ebola outbreak were inundated by partners and overwhelmed by multiple demands. When these partners cannot come together in a coordinated way, they dissipate their collective energy. Per its constitution, WHO is the United Nations (UN) agency for health and is the coordinating and directing authority for all health matters. However, WHO must balance this role with a country’s desire to have visibility and credibility in responding to
5 See http://www.who.int/intellectualproperty/documents/thereport/ENPublicHealthReport.pdf?ua=1 (accessed October 30, 2015).
an issue. Chan remarked that there need to be incentives for governments to take (and to receive credit for taking) action, instead of being forced into action by WHO or other partners. In this regard, what is the duty and responsibility of a country after it signs on to the IHR? She referred participants to the external reviews of the global responses to Ebola and pandemic H1N1 influenza outbreak, which note that member states have largely failed to implement core IHR capacities6 (Fineberg, 2015). When the WHO Director-General is informed in a timely manner of all outbreaks, an assessment can be made about the scale and complexity of the outbreak, what type of response is appropriate, and what role WHO will play. A lesson learned, she said, is that a lot can be accomplished on an informal basis as a result of discussions and relationship building.
6 See Report of the Ebola Interim Assessment Panel—July 2015, http://www.who.int/csr/resources/publications/ebola/ebola-panel-report/en (accessed October 30, 2015), and Alert, Response, and Capacity Building Under the International Health Regulations (IHR), http://www.who.int/ihr/review_committee/en (accessed October 30, 2015).
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