In Sierra Leone and Guinea, the NIAID deputy director for clinical research established initial relationships within the countries. However, Corps officers found themselves in regular interactions with regulators in the Ministry of Health to ensure that applications were complete and import permits for incoming shipments were cleared. Additionally, the research collaboration in Sierra Leone was coordinated through an investigator assigned to a military hospital converted into an ETU. The Corps officers were well suited to maintain and build on that relationship in expanding the protocol to other ETUs throughout Sierra Leone. A site established by the CDC within the Sierra Leone Ministry of Health coordinated ZMapp storage. The Corps officers formed working relationships with the CDC team to establish and improve cold-chain logistics and transportation of the ZMapp to the various ETUs around the country. Corps officers were integral in working with the in-country contract hiring agency. Activities included establishing criteria for clinical research positions, providing input on the interview of respective candidates, and training staff as the team formed. In Sierra Leone, local staff members were hired to work at specific facilities as research coordinators working with the health care delivery teams.
The U.S. team consisted of a physician, nurse research coordinator, and a pharmacist travelling to the sites with a logistics/operations staff member remaining in Freetown.
Fortunately, a Corps nurse on the team had been part of the initial MMU deployment and was trained to work in a special care unit at the NIH for patients with highly contagious infections. This practical experience was essential in the establishment of procedures in a hazardous environment for the administration of the IV ZMapp, monitoring of adverse effects (AEs), provision of medications to mitigate infusion-related reactions, and documentation of those AEs.
The U.S. research team regularly departed Freetown early in the morning 7 days a week with the various supplies needed as they visited up to 4 ETU sites to prepare the ZMapp at the site, await information on any AEs, and collect case report forms (Figures 1 and 2). The ETUs were spread out over a 90-mile radius and could be described as austere platforms for health care delivery.
An additional challenge was dealing with the multinational organizations that staffed the various ETUs. Relief organizations from Italy, the United Kingdom, China, as well as the Sierra Leone military provided the staffing for the 4 ETUs. Regardless of who operated the ETU, the concept of randomization to ZMapp or standard of care required significant tact and diplomacy in communicating the scientific necessity in order to appropriately answer the research question. As Davey and colleagues pointed out, the randomized, controlled trial established the appropriate ethical framework to determine whether the research intervention was associated with harmful effects as there had not been a phase 1 safety study with the drug.13
As the summer approached in Sierra Leone, the team worked through challenges in the IV administration of ZMapp as the protein structure of the monoclonal antibody had not previously been subjected to West African environmental extremes. A balance between speed of administration to prevent protein aggregation in the heat as opposed to the risk of infusion reactions from a foreign protein required the team to communicate frequently with, the manufacturer of ZMapp, to establish realistic infusion rate tables. Additionally, as the various deployment teams rotated in and out, procedures for establishing continuity of research operations were enacted and improved on with each rotation. Good documentation practices to adequately collect all required study information (eg, recording AEs, deviations, and signatures on various forms) proved critical to continuity of research operations.
In Guinea, not only was there the new wrinkle of working within a country where the primary language was French, but also a French cosponsor, Inserm. The NIAID clinical director capitalized on the research infrastructure established for a recently completed Inserm study of favipiravir in the treatment of Ebola to extend the ZMapp study to Guinea. Fortunately, many of the Inserm staff were bilingual and readily responded to the NIH training on the requirements of the ZMapp protocol. However, procedures for cold-chain storage and transportation needed to be established. In Guinea, the PHS officers were key in establishing access and temperature monitoring procedures for a secure room inside the U.S. embassy. The issues associated with cold-chain procedures in the infrastructure-limited environments of West Africa are substantial and warrant consideration of a stand-alone paper. Corps officers also took part in weekly country-focused team meetings with embassy staff to describe progress with the ZMapp study.
As the epidemic waned and NIH transitioned to the survivor and viral persistence studies, the operational tempo changed to allow Corps officers to take part in more definitive capacity building efforts. An initial PHS volunteer from the FDA accepted a position within NIAID as a clinical research oversight manager for pharmacy operations. This individual deployed on numerous occasions to the 3 affected West African countries to further establish cold-chain processes for pharmaceuticals and biologics. He also worked with a multidisciplinary team to renovate a clinical research facility in a rural setting in Guinea. In Liberia, he coordinated an effort with other Corps officers to provide educational seminars on clinical research principles and drug-specific topics with the University of Liberia School of Pharmacy.
