Clinical Investigation During Public Health Emergencies: The Resilience Intelligence Network

Significant knowledge gaps exist for resilience, preparedness, and response to public health emergencies (PHEs) in the United States. The 2009 H1N1 influenza pandemic and natural disasters (as experienced in Texas, Florida, Puerto Rico, and the Carolinas during the hurricane seasons of 2017–2018) highlight missed opportunities for clinical investigation to identify and address strategic vulnerabilities, gaps, and solutions. In response, US government leaders initiated a call to action to include research as part of PHE activities.¹ Progress has been made since then, thanks to new funding that created organizations and infrastructure to lead change for knowledge acquisition and management.^1–3 This progress is essential to answering key clinical questions in response to PHEs.² Similar challenges worldwide are driving creation of unique solutions, such as the Platform for European Preparedness Against (Re)emerging Epidemics, the Australian Partnership for Preparedness Research on Infectious Disease Emergencies, the Canadian Critical Care Trials Group, the Mexican Emerging Infectious Disease Clinical Research Network (La Red), and the International Severe Acute Respiratory and Emerging Infection Consortium.

In the United States, clinical and population research gaps exist in part because of the challenges of coordination and funding.⁴ Closer, more inclusive collaboration remains an essential strategic imperative, given that resilience, preparedness, and response require coordination across a broad range of stakeholders.⁴ The US Department of Health and Human Services (HHS), for example, has no single or overarching source of funding for resilience and preparedness: each HHS agency has a distinct budget that promotes funding “in its lane.” In addition, investigators may be unaware that funding for a similar or complementary aim is provided to colleagues in the same city by a different agency. The current process also is inefficient, requiring the building and disassembling of infrastructure with each funding cycle to answer questions and test hypotheses iteratively. Opportunities for synergy and sustained inquiry are missed. At present, a comprehensive PHE response vision can only result from piecing together separate funding sources and rapidly assembling collaborative partnerships.

These challenges and opportunities were a focus of a recent National Academy of Medicine workshop aimed at expanding capabilities and scale to assess medical countermeasures used during PHEs.⁴ Out of this workshop came a consensus that a structured, collaborative approach of investigator-initiated clinical trial networks, a “Network of Networks,” is required to foster resilience, preparedness, and response. This new effort will require federal partners to provide strategic direction and future sustainability for implementation. The rationale for this multinetwork, multiagency approach is to provide expertise across the clinical care and patient age continuums that leverages complementary and unique experiences and skill sets as well as past investments in research infrastructure.

The Network of Networks for resilience, preparedness, and response (now called the Resilience Intelligence Network) will address historical hurdles by convening regular meetings of all stakeholders, building shared core infrastructure, and utilizing a multiagency, all-hazards approach (see the box on page S269). This combined approach will permit the conduct of high-quality, high-yield clinical research to meet immediate and long-term PHE-specific needs.¹ Clinical research networks are uniquely qualified for these pursuits, with research expertise, access to patients, local knowledge, government partnerships, and existing multidisciplinary teams. A key element of this approach is to get stakeholder groups together to think expansively, leverage existing funding, and seek needed resources. The approach also fosters rapid development of consensus solutions to achieve standardization of clinical and epidemiological data collection, real-time data and specimen analysis, rapid feedback of findings to clinicians to inform clinical management, and implementation of clinical trials that test therapeutics and other medical countermeasures. A significant strength is that broad patient groups are represented by the Resilience Intelligence Network. This is essential, as emerging threats may affect one population more than another (e.g., disadvantaged children or the elderly). Similarly, the inclusion of diverse patient care facilities (academic and community, urban and rural, inpatient and outpatient) ensures catchment of a broad and relevant sample of patients.

BOX 1— Resilience Intelligence Network Participating Networks.

Collaborative Pediatric Critical Care Research Network (CPCCRN)

Discovery Program for Resilience and Emergency Preparedness (Discovery PREP)

Emergency Medicine Transmissible Infectious Disease and Epidemic Network (EMTIDE)

National Ebola Training and Education Center (NETEC)

Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI)

Pediatric Emergency Care and Applied Research Network (PECARN)

Prevention and Early Treatment of Acute Lung Injury Network (PETAL)

Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN)

One immediate impact of this new collaborative approach is to optimize the scale of the effort. The eight networks represented at the 2017 and 2018 Network-of-Network gatherings oversee approximately 180 research sites distributed across the United States and North America. In addition, these meetings provide a unique opportunity to accelerate innovation across the care continuum by scaling the successes of individual networks. Fundamental to this innovation is embracing resilience as an approach to develop the sustained ability of communities to withstand and recover from public health threats. Instead of exercising annually for a potential event, we seek to develop everyday competencies at the community level that minimize the impact of unpredictable public health stressors. This requires building a culture that enhances health system care coordination and assists in empowering and training individuals. This emphasis on resilience will help eliminate duplication, saving both on investigative efforts for clinicians and on resource utilization by governments, health care systems, and public health. These activities will include community hospital perspectives and those of diverse populations that inform the national conversations on resilience, preparedness, and response. Finally, these meetings provide a cohesive and efficient mechanism for those in the United States to partner with national clinical research organizations, professional organizations, and international colleagues.⁵

As pragmatic next steps, we divided the work of the Resilience Intelligence Network into work streams, which in aggregate provide a comprehensive approach. Progress of each stream is tracked quarterly and summarized at annual face-to-face meetings. Leaders of each work stream are tasked with reaching out to Network participants to identify and engage interested members. Expectations of each work stream include holding regular video conferences and planning strategically for annual deliverables that complement the aims of individual networks, including progress on establishing common data elements for clinical studies and a national educational campaign. Seasonal influenza was identified as a public health threat that can serve as a test case for annual exercises that identify resource supply–demand imbalances, evolve capabilities, and expand scale (including the conduct of platform trials). Administrative preparedness will be an additional important area for progress, including toolkits, review of human participant research, and a single centralized institutional review board for research emergencies nationwide. Finally, the group identified the need for rapid technological innovation toward data convergence and interoperability that fosters real-time knowledge management.

Success for this program will require resources to support clinical research infrastructure and project-specific needs, with opportunities for governmental funding and private foundations to lay the groundwork for strong private–public partnerships. This is not a hypothetical need. During seasonal influenza outbreaks from 2010–2011 through 2017–2018, an estimated 140 000 to 960 000 hospitalizations and 12 000 to 79 000 deaths occurred in the United States per season.⁶ Working to improve clinical management of patients with seasonal influenza, including conducting interventional clinical trials, will also better prepare clinicians for the next influenza pandemic.⁷ As experienced during the 2013–2016 West Africa Ebola virus disease outbreak, even a small number of patients infected with pathogens with the potential to cause severe and explosive epidemics can be extraordinarily disruptive to national operations, as well as very costly to public health and acute care hospitals. This is especially true if local facilities are unprepared and medical countermeasures are unavailable (or available but untested).

Finally, the impact of natural disasters on public health (such as hurricanes, tornadoes, floods, and fires) emphasizes the importance of on-demand, real-time clinical data collection, analytics, and rapid dissemination of information. A necessary next step for the Resilience Intelligence Network is to procure substantial, enduring funding for capacity building, translational clinical research, and exercises. Without continuous funding, the capabilities and scale necessary to optimize preparedness, response, and resiliency will be suboptimal, increasing the morbidity, mortality, and cost of public health emergencies. Additional information about the approach, activities, impact, and composition of the Resilience Intelligence Network is available at https://www.rinetwork.org.