The Ebola epidemic of 2014-2016 challenged many federal agencies to find creative ways to help address the vexing problems created by the spread of the disease. There were many factors complicating the response, including the recovery from civil wars in Liberia and Sierra Leone that decimated the physical infrastructure as well as education and other vital services.
The response from the U.S. and the global community took many forms: Not only was there a need for the typical medical care support, but also for basic public health systems to track the spread of disease, provide clean water, and dispose of infectious waste. Because no known preventive vaccines or therapeutics existed for those infected, the recognition of a research component to the response became abundantly clear as the epidemic continued. As a result, the National Institutes of Health (NIH) and the USPHS Commissioned Corps (Corps) serendipitously found themselves allied in a mutually beneficial relationship in the establishment of an Ebola clinical research program in West Africa.
This article describes the events that led to the NIH and Corps participation in the Ebola response, the roles filled by the Corps in supporting the NIH, and the lessons observed from that collaboration. Also presented are considerations regarding preparation of a clinical research response to future outbreaks.
NIH Clinical Research first Response
The 2014-2016 Ebola epidemic in West Africa demonstrated the need for federal agencies to reassess their capacity to respond to global threats to protect the health security of the U.S.1 The outbreak also challenged the U.S. government to mobilize unique resources that matched the need of this international (and domestic) response.
In 2014, President Barack Obama announced that the U.S. would launch a government response to the Ebola effort. Although a comprehensive research and development program already was in place to establish Ebola virus disease (EVD) countermeasures, no FDA-approved diagnostics, therapeutics, or preventive vaccines were readily available. Fortunately, FDA regulations regarding emergency use authorizations allowed for the use of several EVD diagnostics during this outbreak.2 However, the development of drugs and vaccines specific to Ebola had yet to make their way to phase 1 safety studies.
Two vaccine products went into phase 1 studies in the U.S. within months of the declaration of the emergency.3,4 Additionally, the NIH had organized a collaborative effort between the U.S. government and academic community to identify a research strategy for the evaluation of therapeutics.5 Regardless of the state of countermeasures and research proposals, the initial need was for disease control measures and care for Ebola patients. The CDC took the lead in working within the international community to establish an incident management system that could help the impacted countries enact mechanisms to bring the epidemic under control.6
As the epidemic progressed, leaders in the Corps and the NIH responded on pathways that eventually would intersect. One of the unfortunate outcomes of the early efforts of improperly protected health care providers was the unintentional transmission of Ebola.7 The Corps identified the need to provide high-level care to the health care worker community as one incentive to motivate health care workers to volunteer for hazardous duty inside Ebola treatment units (ETUs).8,9 Engulfed in the epidemic response, the U.S. government through the National Security Council and secretary of the Department of Health and Human Services (DHHS) evoked its statutory authority to deploy the Corps (42 U.S. Code 204a).
In the first week of October 2014, the Corps sent an advanced echelon team to assess the situation, partner with key host country and international stakeholders, and begin establishment of the U.S. government’s first ever ETU. With logistics, security, and resource support from the DoD and response coordination from the U.S. Agency for International Development, the Corps then deployed the first of four 70-person team rotations to staff the Monrovia Medical Unit (MMU), an ETU specifically dedicated to the treatment of Ebola-infected health care workers. At the time, it was the only ETU specifically dedicated to health care workers in all of Africa. The MMU operated until May 2015 and provided direct patient care for health care workers with Ebola, malaria, and other illnesses.8,10
In August 2014, representatives from the CDC met with Liberia’s Minister of Health and Social Welfare Walter T. Gwenigale, MD, to discuss the range of available options that could facilitate a better understanding of the prevention and treatment of the disease. This meeting resulted in a letter dated August 22, 2014, from Dr. Gwenigale to then DHHS Sylvia Burwell, requesting a research response. Secretary Burwell responded on October 2, 2014, describing the immediate dispatch of the deputy director for clinical research of the National Institute of Allergy and Infectious Diseases (NIAID) to Liberia to engage in initial discussions with the Liberian minister and other key Liberians involved in the response.
Representatives from the CDC and the commander of the Corps’ Ebola response (and acting deputy surgeon general) were included in those initial meetings, which led to a recognized need for a robust clinical research program of the highest ethical and scientific standards consistent with the expressed requirements of Liberia.11 A second and third trip to Liberia with larger U.S. teams resulted in an agreement signed on November 19, 2014 for the scientific investigation of strategies that tested interventions for treatment, control, and prevention of Ebola.12
The agreement led to the establishment of the Partnership for Research on Ebola Virus in Liberia (PREVAIL) to identify research priorities in a collaborative manner between Liberian and American scientists. The first protocol, a vaccine study, was launched in early February 2015.12 This monumental task involved the support of hundreds of Liberians and dozens of NIH staff who volunteered for rotations to Liberia. Of the 108 volunteers from within the NIH, 18 were PHS officers. Shortly after launching the vaccine study, the next priority was initiating the treatment study. This study was delayed primarily due to ZMapp (Mapp Biopharmaceatical, San Diego,CA) production limitations. ZMapp, a monoclonal antibody cocktail, was the first Ebola therapeutic product to be evaluated in a randomized trial.5,13
During the planning for the study, NIAID staff in Liberia met with Corps staff of the MMU to discuss the logistics associated with implementation of the ZMapp protocol at the MMU. During that meeting, the NIAID deputy director for clinical research expressed interest in obtaining Corps support from outside the NIH to sustain the research effort in West Africa. More specifically, additional pharmacy and laboratory staff were needed to augment NIH research operations. At the time, the MMU commander had recently transitioned from service as the acting surgeon general and was in a unique position to recommend additional Corps resources that could help in the research response.
The February 2015 discussion resulted in the establishment of an NIH/PHS research partnership that continues to exist. This new opportunity was not a significant stretch for the PHS as there was great interest from the Corps for responding to the Ebola crisis. The enthusiasm was consistent with the overall ethos of the Corps, which as a service was composed of highly qualified active-duty, deployable, uniformed, public health professionals who respond to public health crises at home and abroad. To date, 19 Corps officers from outside the NIH have deployed in support of the NIH Ebola clinical research program. An additional 18 Corps officers assigned within the NIH also volunteered for duty in West Africa. Of the 37 Corps officers supporting the NIH clinical research program, 7 served on more than 1 rotation.