FREDERICK, Md. -- “Sure, it’s easier than doing research in more isolated places, say Antarctica, or outer space—but that does not make it easy for those on the ground. Sometimes densely populated areas pose problems of their own. Not everyone agrees on the need, the presence of so many ‘outsiders,’ or on the approach taken. People were attacked. Research sites were burned.”
Marc Teitelbaum, M.D., is referring to the international team currently doing Ebola clinical studies in the Democratic Republic of the Congo. In the 16 months since an outbreak was declared in the country’s Kivu region, more than 2,200 people have succumbed to the disease, while fear and distrust of medical teams have fueled unrest, and armed rebels have assaulted and razed treatment units.
Yet, in a display of unity and courage, the team has completed a study fittingly named Pamoja Tulinde Maisha (PALM), which is Kiswahili for “together save lives.” Despite the violence and challenges, they collected high-quality data and found that two experimental treatments—including one largely manufactured at the Frederick National Laboratory—significantly improved patients’ survival. The results, which were announced in August and recently published in the New England Journal of Medicine, have been nominated for Science magazine’s 2019 People’s Choice for Breakthrough of the Year. Both treatments are now being given to patients in a follow-up study.
“It’d be hard for somebody to say, ‘Oh, well, you can never do that kind of research because it’s just too difficult,’ in the future, because this was kind of the big daddy of difficult research,” said Teitelbaum, the sponsor medical monitor on PALM and the director of clinical safety in the Frederick National Laboratory’s Clinical Monitoring Research Program Directorate.
Strengthening the Congo
PALM was co-sponsored and funded by the Democratic Republic of the Congo’s National Institute for Biomedical Research and the U.S. National Institute of Allergy and Infectious Diseases (NIAID). Several organizations rallied to help. The Frederick National Laboratory was tasked with supporting PALM through its successful partnership with NIAID. The Congolese Ministry of Health, The Mitchell Group, the Alliance for International Medical Action, Doctors Without Borders, International Medical Corps, the World Health Organization, and others also contributed significant resources, personnel, and labor.
However, as Calvin Proffitt, general operations manager in the national laboratory’s Clinical Monitoring Research Program Directorate, points out, that support was coordinated to empower the Congolese medical community, not paternalistically handle the crisis on its behalf.
“[The Congolese staff] are leading it. This outbreak, they’re living it. This is their world,” he said. The Congolese response was led by Professor Jean-Jacques Muyembe-Tamfum, M.D., Ph.D., co-principal investigator on PALM and director-general of the National Institute for Biomedical Research.
The goal was to perform a successful clinical study while preparing the Democratic Republic of the Congo to respond to future outbreaks with more experience in using sophisticated laboratory equipment. By providing equipment, training, and expertise, NIAID and the Frederick National Laboratory helped cultivate a well-prepared cadre of Congolese personnel to bolster the nation’s existing scientific and support staff.
The Frederick National Laboratory also helped build a medical infrastructure that addresses the Democratic Republic of the Congo’s current and future needs. Proffitt, his colleagues, and collaborating teams coordinated the study’s staffing and logistics. They worked with The Mitchell Group, which hired Congolese citizens to care for infected individuals enrolled in the study and recruited U.S. staff to augment the Congolese teams. Proffitt’s team also helped to ship critical clinical materials from the U.S. to the Ebola treatment units in the Kivu region, more than 7,000 miles away.
Meanwhile, Teitelbaum’s team monitored data integrity and patient safety during the trial, often working evenings and weekends to keep up with the massive workload and address urgent amendments and questions. As sponsor medical monitor, Teitelbaum reviewed and edited drafts of the study’s protocol and, along with Kelly Cahill, R.N., clinical research oversight manager at NIAID, served as a primary point of contact for answering study safety questions.
The Clinical Monitoring Research Program Directorate also facilitated routine conference calls with the Congolese researchers, NIAID, and other collaborators to keep the trial on track. At times, Proffitt, Teitelbaum, and Frederick National Laboratory staff traveled to the Democratic Republic of the Congo’s capital, Kinshasa, to work alongside other groups supporting the trial.
Many additional teams at the Frederick National Laboratory—including scientific, acquisitions, purchasing, logistics, shipping, property, and clinical manufacturing staff—contributed to PALM’s success and provided support ranging from drug manufacture to inventory management.
Heroes in the Clinics
Except for one employee, Ian Crozier, M.D., Frederick National Laboratory staff haven’t worked in the Ebola treatment units due to contractual and security restrictions. Proffitt and Teitelbaum say that represents the key difference between their efforts and those of the clinical teams. While the national laboratory employees work in the U.S. and Kinshasa, PALM staff in the Kivu region repeatedly confront tremendous danger.
“They show up, they work, and they eagerly leave Kinshasa to go to the east amidst Ebola and armed conflict, where it’s not easy to get from point A to point B,” Proffitt said. “Seeing the resolve and the courage displayed was really just very humbling.”
Teitelbaum recalls one terrifying conference call when the clinical staff on the other end of the line suddenly began whispering that they could hear gunshots nearby, a rebel group roaming the vicinity.
“It gives me chills now,” he said. “Sitting here safely, listening to this phone call, this isn’t some TV show; this is their reality. … They’re trying to do the good work, and this is what they’re dealing with.”
Despite extensive precautions, clinical staff also could contract Ebola while caring for and monitoring patients. If infected, they face a mortality rate of 25–90 percent, depending on the quality of treatment and the time at which it’s administered.
“It’s not just the shooting, it’s not just the people setting fire to their research site, it’s not just the hours and the horrible things that they have to see and put up with, it’s the fact that if [they] make a mistake, [they] get Ebola and could die. And the odds are more rather than less that [they would] die, and yet they keep doing it,” Teitelbaum said.
“One Patient at a Time”
Amid the horror and the danger, there have been brighter moments. At the treatment unit in Butembo, caregivers celebrated the discharge of a healthy Ebola survivor by cheering in the dirt streets among the buildings and prefabricated medical tents.
Many researchers in the Democratic Republic of the Congo and the U.S. have formed friendships and professional relationships, tested and tempered in the crisis. Teams that previously knew little of their foreign counterparts have developed rich collaborations that can produce meaningful research in the future.
“I can’t wait to see these folks again,” Teitelbaum said of his plan to visit the Congolese scientists at an upcoming conference. “They are heroic to me. … I really feel like I have the most amazing, I would say, friends and collaborators in the Congo.”
The study staff have also helped some patients in unexpected ways. At one point, a patient gave birth to a baby who had a severe birth defect and needed surgery in order to have a relatively normal life. Despite the peril of the Ebola outbreak, a pediatrician traveled to the treatment unit and oversaw efforts to care for the child, while other personnel coordinated safe transportation to a site for the surgery. For weeks, a segment of the staff conference calls was dedicated to updates about the child’s condition.
“That this massive, massive senior international team stopped and listened to this story, that goes to our humanity, and that goes to the fact that, ultimately, it comes down to one patient at a time,” Teitelbaum said.
By Samuel Lopez, staff writer
Top image: Families go to the Ebola Treatment Center to visit a family member who is held in quarantine. [Credit: World Bank/Vincent Tremeau, republished here under CC BY-NC-ND 2.0]
Bottom image: Dr. Marie-Claire Kolié of the World Health Organization (left) and Dr. Ian Crozier, Frederick National Laboratory/NIAID, deployed by WHO, at the Butembo Médecins Sans Frontières (Doctors Without Borders) Ebola Treatment Unit. [Credit: NIAID]Tagged: