In October 2014, President Obama stated that he considered the Ebola outbreak and response “a top national security priority.”1 The Global Health Security Agenda and the 2015 National Security Strategy include preparedness and response to infectious disease outbreaks.2 Although several presidents have recognized that epidemics of infectious disease are a national security concern, multiple pieces of legislation have been drafted and passed, and new organizations created to address epidemics, we continue to lament the lack of capacities for timely and adequate responses. As illustrated in Chapter 2, gaps in international response capability persist, and according to Parker at Texas A&M Health Science Center, reports suggest that the global community is ill prepared for the next epidemic or pandemic. In this chapter, experts representing a variety of sectors (e.g., national security, biosecurity, defense, economics, risk, industry, and ethics) discuss their perspectives, focusing on what can be done during interepidemic periods to envision MCM availability through a lens of national security, fill the gaps in preparedness, and enhance MCM capabilities.
The emergence of a new and more dangerous infectious disease is what economists such as Robert Shapiro, co-founder and chair of
1See https://www.whitehouse.gov/the-press-office/2014/10/06/remarks-president-after-meeting-ebola (accessed June 30, 2015).
2See http://www.cdc.gov/globalhealth/security/ and https://www.whitehouse.gov/sites/default/files/docs/2015_national_security_strategy.pdf (accessed June 30, 2015).
Sonecon, LLC, refer to as an exogenous event—one that comes from outside the economy, so it is unpredictable. A strong economy may mitigate the impacts of exogenous shocks, while a weaker economy can suffer lasting negative effects. Shapiro likened a strong economy to a society that is prepared for the outbreak of a dangerous disease. In predicting the potential impact that a shock (i.e., outbreak) will have on the society, one needs to consider all of the following: who is in charge, how vital data and information are obtained, how reliable those data are, whether the dissemination of key information is well managed and controlled, whether concrete measures are in place with resources to isolate and control the spread of the disease, and whether there are facilities ready to develop new treatments to rapidly produce them and efficiently distribute them.
The effects of an exogenous shock on the overall economy depend on two dimensions: how widespread the effect of the shock is and how long the effects are sustained. A shock that is fairly localized and does not last long (e.g., a hurricane or the 9/11 terror attacks) has little macroeconomic effect. This kind of event, however, has distributional effects. Following the events of September 11, 2001, for example, Lower Manhattan real estate values fell, but those in Midtown rose; hotels and airlines suffered temporarily, but consumers instead spent their money on televisions and recreational vehicles; the federal government cut interest rates, boosting interest rate-sensitive industries. These dimensions also apply directly to the economic effects of an unanticipated natural disease outbreak or intentionally released infectious agent (e.g., whether it has the potential to become a pandemic, spread over a wide area for a protracted time).
Much of the economic cost of disease outbreaks arises, not from direct effects but from public anxieties because of misinformation about the spread of disease and lack of clear or appropriate leadership response at the outset. Economic effects of an event become nonlocalized as a result of large-scale quarantines, disruption of business, calls to close schools and cancel large public gatherings, and demands to suspend air flights and close borders between states. Public panic, either financial or otherwise, is the absence of reliable information. Shapiro indicated that information must be followed with concrete measures that effectively contain and treat the infection. These conditions emphasize the critical need for advanced investment and planning, including the designation of a credible agency or person in charge who can allay fears and disseminate credible information.
In a world of limited resources, the public resources to plan and prepare for a pandemic almost certainly must come from spending for another public purpose or from additional taxes, he said. However, people are generally unwilling to bear short-term costs in order to avoid a larger unknown long-term cost. Given this political reality, Shapiro suggested the idea of a philanthropic-financed entity, perhaps working with the Centers for Disease Control and Prevention (CDC), that would examine the level of state and federal preparedness and recommend steps to better plan and prepare. This could be accompanied by a new tax incentive for pharmaceutical firms to establish facilities that could quickly produce vaccines and treatments for emerging infectious disease outbreaks.
What is needed now, according to Suresh Kumar, senior partner at Oliver Wyman Public Sector and Health and Life Sciences Practice, Marsh & McLennan Companies, is an objective, outside-in global health security strategy for the future. This strategy would consist of enabling frameworks for raising money; conveying resources and services to affected populations; establishing policies and protocols that enable the development of innovative products, programs, and pathways; and understanding and sharing risks, liabilities, and responsibilities to preempt, combat, and contain infections. He agreed with others that industry is going to be part of the solution and needs to be involved at the start.
World Economic Forum: 2015 Global Risk Report
Marsh & McLennan produces an annual global risk report for the World Economic Forum. The report is based on an annual Global Risk Perception Survey of more than 900 leaders and decision makers from business, the public sector, and academia to identify risks, their potential impact, and the likelihood of occurrence. Of concern, Kumar said, is that rapid and massive spread of infectious disease made the list for 2015 after a hiatus of 6 years, and was ranked second for risk in terms of potential impact.3
3See http://www3.weforum.org/docs/WEF_Global_Risks_2015_Report15.pdf (accessed June 30, 2015).
An epidemic like Ebola is not an African problem. It is a global problem, a human problem, the solution for which lies in building local, regional, and global collaborations and shared responsibility.
— Suresh Kumar, senior partner
at Oliver Wyman Public Sector
and Health and Life Sciences
Practice, Marsh & McLennan
The 2015 report delineates risks from trends and the interrelationships between them that could be a cause for further concern. A global risk is an uncertain event or condition that, if it occurs, can cause significant negative impacts for several countries or industries within the next 10 years, he explained. By definition, it is not always predictable, but one can prepare for it. A trend, he said, is a long-term pattern that is currently taking place and that could contribute to amplifying the global risk and/or the relationship between them. Unlike risk, trends occur with certainty and can have positive or negative consequences. Global health security concerns will be exacerbated by trends toward rapid and unplanned urbanization, particularly in developing countries; inadequate infrastructure associated with water, electricity, and sanitation; increasing resistance to antibiotics and antiviral drugs; and growing human mobility, which compounds the risk of transmission.
Kumar stressed the need for agreement on what constitutes global health security and alignment on risk mitigation pathways (e.g., building resilience, resource mobilization, treatment of infected patients/health care workers, identifying and isolating infected people versus quarantines and embargos). The response to the EVD outbreak has exposed a globally broken, antiquated system where efforts are likely duplicated, technology is inadequately leveraged, and resources are not optimally deployed. Mistrust between donors and recipients persists, donors demand accountability, and recipient countries are uninspired to work with external experts who come and go with each crisis, failing to build sustainable institutions or capabilities.
Facilitating pathways need to address issues such as ownership of intellectual property, liability, regulatory pathways, technology, new hospitals/prefab modular hospitals, telemedicine, and training of health workers. Kumar stressed that each person needs to move the conversation in his or her area of expertise. Furthermore, this is a global problem that calls for a confederation, not multiple localities addressing their unique needs. A participant noted that outbreaks are going to start and spread from countries where the United States and other major powers do not have access, such as those in the Middle East or northern
Africa. Venkayya said that, if a health agency is in charge, it must be complemented by the diplomatic and security apparatus necessary to execute a response. The United Nations and influential governments must use their diplomatic, financial, and other levers to encourage governments of impacted countries to do the right thing, he advocated.
Infectious diseases, whether naturally occurring, accidentally released, or intentionally caused, continue to threaten U.S. military personnel and their beneficiaries, both at home and abroad, said Commander Franca Jones, medical director of the Office of the Deputy Assistant Secretary of Defense for Chemical and Biological Defense Programs. Therefore, the Department of Defense (DoD) plays a critical role in global health security through ongoing threat reduction and MCM development programs for their personnel, as well as through enforced health protection efforts.
Within DoD, the Chemical and Biological Defense Program is charged with developing capabilities to enable the warfighter4 to deter, prevent, protect against, mitigate, respond to, and recover from chemical and biological threats and their effects. Specifically, the program’s efforts to develop MCM, which include prophylaxis, therapeutics, diagnostics, and biosurveillance information systems, all support this mission as well as the U.S. Global Health Security Agenda.
Applications to the Civilian Sector
Because biological threats range from common infectious diseases to the potential for complex engineered organisms, the DoD program uses an integrated layered approach, seeking holistic solutions, not just for individual agents, but potentially for classes of agents, that protect the warfighter both from the inside and the outside (e.g., personal protective equipment, decontamination, MCM). The program relies on requirements provided by the warfighter, and programmatic efforts focus on solutions for the warfighter. However, much of DoD’s research and development efforts can be leveraged for the broader civilian population, both domestically and internationally. For example, DoD’s Ebola
4The term “warfighter” is used to describe a soldier in combat.
diagnostic test was the first to receive emergency use authorization (EUA) for use in U.S. citizens. As of March 2015, it is the only test used throughout the U.S. Laboratory Response Network and in U.S. laboratories in West Africa. DoD’s early investment in the Ebola therapy, ZMapp, led to that drug’s use in Phase II and III clinical trials. It is important to note that these products were in development years before the current Ebola outbreak due to a warfighter requirement for diagnostic, preventive, and therapeutic capabilities against filoviruses. Ultimately, according to Jones, had it not been for these ongoing efforts, it is less likely that products would have been at a stage to move forward into the field as quickly as they were. As Tara O’Toole, senior fellow and vice president of In-Q-Tel, Inc., pointed out, the DoD Ebola diagnostic test was able to quickly be applied for field use, while vaccines and other countermeasures being developed still take many months of trials and analysis before use in the field, highlighting the importance of supporting point of care diagnostics to assist in rapidly halting epidemics.
Prioritization of Threats for the Warfighter
It is impossible to stay ahead of every threat that may present itself. Within the DoD, our strategy is to develop broad solutions that may have application to multiple threats.
— CDR Franca Jones, medical director
of the Office of the Deputy Assistant
Secretary of Defense for Chemical and
Biological Defense Programs
DoD must balance its work against a broad range of threats, including nuclear, chemical, biological, radiological, explosive, cyber, and others. Even within the biological threat, there are multiple viruses, bacteria, and toxins. To prioritize, DoD thinks about how best to reduce risk to the warfighter. The strategy for MCM development focuses first on those agents that have a high mortality rate, are rapidly lethal, spread rapidly from person to person, or put a warfighter out of the fight for a prolonged period of time. Second, DoD works toward being able to rapidly field certain countermeasures through “interim field capabilities,” such as pre-EUA packages submitted to the FDA, or through contingency investigational new drug applications (INDs). DoD also encourages the development of broad-spectrum MCMs that address both current clinical needs and emerging infectious diseases. Finally, DoD coordinates efforts domestically
through the ASPR Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), as well as with international partners, to provide synergistic value.
Jones said that, during the recent Ebola outbreak, although DoD did have products available, initiating clinical trials was very difficult. Therefore, she recommended the development of protocols for randomized controlled clinical trials through WHO and other organizations, with buy-in from countries that have the minimum essential elements to be prestaged as clinical protocols. Many trials that are ongoing in these countries are not well designed, will not lead to licensed products, and will not help develop products for the next outbreak, she claimed.
Staying ahead of every threat that may present itself is impossible, Jones acknowledged, and this has been one of the biggest roadblocks. Within DoD, the strategy is to develop broad solutions that may have application to multiple threats. Moving forward, she said, DoD’s international and interagency partnerships will be critical to ensuring that multiple potential threats are addressed by the defense and health sectors with countermeasures to ensure a world safe and secure from infectious disease threats.
O’Toole of In-Q-Tel concurred with others that the public health sector must ask for what it needs, noting that, within public health alone, there is not nearly enough money to construct a sound, strategic biodefense strategy. The nation’s public health sector has been decimated since 2008 by the economic recession, especially at the level of the state health department, which is often where the local response capacity lies. She added that, while those within government are focused on how to sustain their programs and survive, external stakeholders are needed to advocate for what must be built. In the United States, the private sector has always been the prime source of innovation. However, it has become increasingly difficult for private organizations to harmoniously work with government due to a variety of challenges (e.g., cumbersome acquisition systems, risk-averse contract officers, insufficiently funded projects). Therefore, O’Toole advocated, it is necessary to create novel ways in which the government and private sector can work together. One option she suggested is that MCM design and production be moved out
of government and assigned to a new type of organization that is not hampered by government acquisition rules.
Raising the Profile of Public Health
Biosecurity is not a top priority of any agency, O’Toole said. Public health needs a higher profile, including a seat at the National Security Council table, and an agency dedicated to public health, with cabinet-level power that can command the attention and the resources of government committees. Such an agency could begin to illuminate the true costs of what is needed and define how to achieve it, educating policy makers and the American public on why we can expect these epidemics to continue (e.g., human activity in once-remote ecosystems, antibiotics in poultry feed).
Daniel Abdun-Nabi, president and chief executive officer of Emergent BioSolutions, shared his perspective based on more than 15 years of acquiring and developing MCMs for biological and chemical threats for governments across the globe. In 1998, Emergent Biosolutions acquired the anthrax vaccine for development, working in close collaboration with DoD, which was the principal government agency responsible for MCM to protect the warfighter. The 2001 anthrax letter attacks made it clear that anthrax was no longer only a military problem, but also a civilian one. Infectious threats could be natural or human-made, emerging at any time or from any source.
In 2004, Project Bioshield was signed into law, allocating $5.6 billion for the research, development, acquisition, and stockpiling of MCMs for civilian use, through programmatic initiatives that included public–private partnerships. Abdun-Nabi said that the management of Project Bioshield by ASPR’s Biomedical Advanced Research and Development Authority (BARDA) has led to 12 MCMs now in the Strategic National Stockpile (SNS) to address bioterror threats—10 of which are licensed and 2 of which are available under EUAs. He noted that Emergent BioSolutions provided several of those products to the U.S. government under long-term contracts. While this shows some successes and end-stage products, others criticize Project Bioshield because, with $5.6 billion spread across 14 different threats, their awards
are too small to motivate large pharmaceutical companies, and so it has only attracted smaller biotech and pharmaceutical companies (Matheny et al., 2007) illustrating the difficulty in finding a “one-size-fits-all” solution.
The key to the BARDA strategy is collaboration among government agencies and partnerships with industry early in development. Resources from these partnerships are ready to be tapped, Abdun-Nabi said. For example, Emergent BioSolutions has a number of technologies that are relevant to Ebola, but it had not fully developed any of them because they were low in priority as established by the company’s resources and capabilities. However, during the outbreak, the company made a candidate vaccine at risk and subsequently partnered with the National Institutes of Health (NIH), GlaxoSmithKline (GSK), Oxford University, and the Wellcome Trust for further development. Within 90 days that product went from candidate identification to clinical trials. The company has additional assets that could be applied to treating Ebola, including a portfolio of monoclonal antibodies, a polyclonal technology, and a flexible manufacturing facility if opportunities become available.
Abdun-Nabi emphasized that, to attract industry to MCM development, there needs to be a vibrant and sustained market opportunity, including long-term contracts from government for product development, manufacturing, and procurement, and an increase in the integration of financing so there is equity on both sides of the agreement. Long-term agreements with large-scale deliverables can help to establish pricing that is fair and reasonable to the government, while providing reasonable return on investment to pharmaceutical companies. He agreed with others that a more streamlined and simplified contracting process would help to enable pharmaceutical companies and others to enter the MCM space.
A few participants noted that it has been very challenging to induce credible leaders in industry to speak openly to Congress about what they would need to invest in the MCM enterprise. Venkayya at Takeda agreed that it is risky for companies to advocate for government research and development investment in products that will benefit the industry somehow, as it almost always appears self-serving. Sophisticated stakeholders inside and outside of government, including academics and patient groups, also need to validate industry needs and concerns in front of Congress, a participant added. John Rex of AstraZeneca concurred that industry cannot advocate for itself in this area.
Lisa Lee, executive director of the Presidential Commission for the Study of Bioethical Issues, referred participants to the Commission’s recent report, Ethics and Ebola: Public Health Planning and Response.5 The report highlights important ethical dimensions of the predominantly national security rationale for public health action and preparedness. Garnering the political will and the resources necessary for public health action can be extremely difficult, she said. National and/or health security arguments during and immediately following a high profile public health emergency can be quite compelling, both to the policy makers and to the public, who otherwise might be either skeptical or have limited knowledge of public health infrastructure. However, as noted by others, interest and momentum wane between events. Invoking a predominantly national security rationale to address public health problems can be very effective in contributing to policy and programs that strengthen the public health infrastructure, but there are unintended consequences with ethical dimensions and direct practical implications for preparedness.
The Ebola epidemic and other recent disease outbreaks have demonstrated that prevention continues to be undervalued and underfunded, Lee said. It is hard to measure or capture the value of something not happening. Public health emergencies most often arise from long-standing conditions of social injustice and inequity, and the global attention to public health emergencies is often reactive and fear based. Trust in government and meaningful involvement of affected communities are essential to prevent and to respond to emergencies, according to Lee. While pharmaceutical MCMs have had dramatic impacts on public health emergencies involving novel threats, the traditional low-technology, public health practice approaches have been proven to be the most useful in those countries that have successfully averted disaster (e.g., public health surveillance, community engagement, quarantine and isolation, contact tracing).
While deliberate development of ethical, evidence-based public health policies is essential in a society committed to global public health, public health experts and policy makers would be remiss if they did not also attend to the health security implications. As outlined by the Commission in its Ebola report, there are both ethical and prudent
reasons for U.S. engagement in response to public health emergencies. Ethical reasons are both humanitarian and justice based. Health is a global public good, and from a humanitarian perspective, the suffering of others demands action. Social justice, which Lee said is a central ethical foundation of public health, involves a commitment to sufficient levels of health and well-being, regardless of location or national affiliation. Beyond ethics, prudence acknowledges that our national interests are clearly tied to the interests of others.
Unintended Consequences of a National Security Lens
Lee highlighted some of the possible unintended consequences of a predominantly national security or health security orientation to response. All parties are best served by a broad approach to what constitutes both health and national security. When public health policy and action are grounded in a narrow definition of national or health security, there can be numerous unintended, often interrelated, consequences that can negatively impact public health efforts. For example, public health programs might be perceived as intended to protect high-income countries against the diseases of the lower-income, afflicted country. This perception can result in stigma, discrimination, and inattention to health problems that are unlikely to affect high-income countries. There is often an emphasis on short-term solutions to control acute infectious diseases when they emerge, rather than long-term efforts to build health infrastructure and address the underlying issues that contribute to the likelihood of such outbreaks (e.g., war, poverty). Other concerns include the increased politicization of health problems, the association of public health programs with misuse of authority, including governmental or military power, and decreased cooperation and sharing in the goals of public health efforts.
Moving forward, it is important to recognize that there are both ethical and prudent interests in working to improve global health, and that the rhetoric surrounding an emergency response can have both clear and unintended consequences.
Andrew Weber, deputy coordinator for Ebola response at the Department of State, stressed the importance of capitalizing on the
momentum from the Ebola response, and referred participants to a recent commentary by Bill Gates on lessons to be learned from the Ebola epidemic (Gates, 2015). Incremental progress has been made over the years, Weber said, but Ebola has once again demonstrated our collective vulnerability. The global population is only as safe and healthy as the weakest links around the world. The response to the EVD outbreak quickly outstripped the capacities of the health agencies of Guinea, Liberia, and Sierra Leone. Despite the largest field deployment by CDC in its history (more than 200 persons), there are still acute shortages of key personnel (e.g., French-speaking senior field epidemiologists for Guinea) to dedicate to this response.
He also noted the long lead time for product development. One year has passed since WHO confirmed the Ebola epidemic in West Africa, and vaccines are still undergoing trials. O’Toole of In-Q-Tel emphasized the need for diagnostics, both laboratory and point-of-care, and said the lack of better diagnostics is a market failure. Weber agreed wholeheartedly, saying that diagnostics are key to global capacity building, and we have been underinvesting in their development and underestimating their value and return on investment. For example, the Naval Medical Research Center Laboratory in Bong County, Liberia, was able to reduce the time to Ebola diagnosis from 5 to 7 days, to 3 to 5 hours. This allowed for the ability to triage cases, rather than sending all those waiting for test results to already overwhelmed Ebola treatment units. He also highlighted the importance of information technology and biosurveillance (including a global, real-time early warning system).
The response needs to be multisectoral and multinational, Weber said. More than 70 countries, and numerous private and philanthropic organizations, have contributed resources, technical expertise, personnel, and money to the response in West Africa. He highlighted the agility and capability of the philanthropic sector in contributing to the response effort and in coordinating different sectors to innovate solutions. Efforts are under way in the private sector to develop three promising vaccine candidates that are currently in Phase II and Phase III clinical trials in West Africa. Preparing the world to prevent and respond to future epidemics requires capitalizing on this extraordinary global effort and international goodwill.
During discussions, Venkayya and Rex raised the issue of sustainability of prevention efforts centered around a vague threat with significant consequences. “We need to use the current crisis, while we temporarily have the world’s attention, to make the threats concrete and
the planned actions clear,” Venkayya said. This entails communicating how government and industry partners are going to share risk and cost in addressing defined targets. There is also a need for leadership in the executive branch to buy into this concept and propose the necessary investments.
Shapiro of Sonecon again highlighted the importance of being very precise and clear about what is actually needed and being requested when advocating for public resources with Congress and the administration. Numerous needs and wants were mentioned in the discussions (e.g., funding for an agency that evaluates preparation and facilities to develop vaccines). The system is very resistant to taking money away from one entity in order to give it to a new entity, and is even more resistant to raising additional revenues. In some cases, mobilizing the public interest can create leverage within the government (e.g., by explaining to the public, as well as the business sector, what would be lost in the absence of securing funding). Kumar of Marsh & McLennan added that budgets are generally set based on the prior year’s budget, plus or minus some amount. In addition to being clear about what is needed, it is important to be very specific about what will no longer be done and what duplications will be eliminated.