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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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INTEGRATING CLINICAL RESEARCH
INTO EPIDEMIC RESPONSE

THE EBOLA EXPERIENCE

Gerald Keusch, Keith McAdam, Patricia A. Cuff,
Michelle Mancher, and Emily R. Busta, Editors

Committee on Clinical Trials During the 2014—2015 Ebola Outbreak

Board on Global Health

Board on Health Sciences Policy

Health and Medicine Division

A Report of

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2017. Integrating clinical research into epidemic response: The Ebola experience. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24739.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
×

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Reports document the evidence-based consensus of an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and committee deliberations. Reports are peer reviewed and are approved by the National Academies of Sciences, Engineering, and Medicine.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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COMMITTEE ON CLINICAL TRIALS DURING THE 2014–2015 EBOLA OUTBREAK

GERALD T. KEUSCH (Co-Chair), Professor of Medicine and Global Health, Boston University Schools of Medicine and Public Health

KEITH McADAM (Co-Chair), Emeritus Professor of Clinical and Tropical Medicine, London School of Hygiene & Tropical Medicine

ABDEL BABIKER, Professor of Epidemiology and Medical Statistics, Medical Research Council Clinical Trials Unit at University College London

MOHAMED BAILOR BARRIE, Co-Founder, Chief Strategic Officer, The Wellbody Alliance

JANICE COOPER, Country Representative, Liberia Mental Health Initiative, The Carter Center

SHEILA DAVIS, Chief Nursing Officer, Partners In Health

KATHRYN EDWARDS, Professor of Pediatrics, Vanderbilt University School of Medicine, Vanderbilt Research Program

SUSAN ELLENBERG, Professor of Biostatistics, Perelman School of Medicine, University of Pennsylvania

ROGER LEWIS, Professor and Chair of the Department of Emergency Medicine, Harbor–University of California, Los Angeles, Medical Center

ALEX JOHN LONDON, Professor of Philosophy; Director, Center for Ethics and Policy, Carnegie Mellon University

JENS LUNDGREN, Professor of Infectious Diseases, University of Copenhagen

MICHELLE M. MELLO, Professor of Law, Stanford University School of Medicine, School of Law

OLAYEMI OMOTADE, Professor of Pediatrics and Child Health, Institute of Child Health, University College Hospital, University of Ibadan

DAVID H. PETERS, Professor, Johns Hopkins Bloomberg School of Public Health

FRED WABWIRE-MANGEN, Associate Professor of Epidemiology and Public Health, Makerere University School of Public Health

CHARLES D. WELLS, Head of Development and Associate Vice President, Infectious Diseases Unit, Sanofi-U.S.

Study Staff

PATRICIA A. CUFF, Study Co-Director

MICHELLE MANCHER, Study Co-Director

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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EMILY R. BUSTA, Associate Program Officer

MICHAEL J. BERRIOS, Senior Program Assistant

OLIVIA YOST, Research Assistant

ELLEN K. KIMMEL, Senior Research Librarian

ANNE B. CLAIBORNE, Senior Program Officer

JULIE PAVLIN, Director, Board on Global Health

ANDREW M. POPE, Director, Board on Health Sciences Policy

Consultants

JANET DARBYSHIRE, Emeritus Professor of Epidemiology, University College London

ERIN HAMMERS FORSTAG, Science Writer

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Reviewers

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:

Dennis Carroll, U.S. Agency for International Development

Geneviève Chêne, Université de Bordeaux

I. Glenn Cohen, Harvard Law School

Patricia Fast, International AIDS Vaccine Initiative

Thomas R. Fleming, University of Washington

Peter Barton Hutt, Covington & Burling LLP

Mohammad Bailor Jalloh, FOCUS 1000

Elaine L. Larson, Columbia University

Heidi J. Larson, London School of Hygiene & Tropical Medicine

Adam C. Levine, Brown University

Susan A. Murphy, University of Michigan

John-Arne Røttingen, Harvard T.H. Chan School of Public Health

Janet Wittes, Statistics Collaborative, Inc.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the report’s conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Georges Benjamin, American Public Health Association, and Lawrence D. Brown, University of Pennsylvania. They were responsible for making certain that an independent examination of the report was carried out in accordance with the institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Preface

In the beginning there was one—a 2-year-old infant from a small village near the town of Guéckédou in the Forest Region of Guinea who, after a brief and dramatic illness, died on December 28, 2013. During January 2014, several immediate family members developed similar symptoms and died too, followed by some of the midwives, traditional healers, and health care workers who attended them. Soon the numbers affected in Guinea were in the tens, then the hundreds, and by the middle of the year in the thousands, now not only in Guinea but also in neighboring Sierra Leone and Liberia. And so the Ebola outbreak of 2014–2015 began and spread, not unnoticed but rather unidentified, and grew to a magnitude never before seen since the virus had first been discovered in 1976. Ultimately the outbreak affected more than 28,600 individuals during 2014 and 2015, with at least 11,310 deaths recorded. This is far more than the total from every outbreak in the 40 years we have known of the Ebola virus.

Clearly the world was not prepared; while some aspects of the response worked, and the outbreak was ultimately brought to a close, many things did not work well at all. In part this was due to the nearly four decades of prior experience with Ebola outbreaks, which were all in relatively remote and isolated communities in central Africa, affecting a few to a few hundred individuals, albeit with a high case fatality rate, before coming to an end as effective public health measures to stop transmission were put into place. With this in mind as the typical pattern, many in the global public health community could not—or would not—believe that 2014 was really different. Health care and public health, like science itself, are built on the cumulative experience of the past, which serves as the basis for our expec-

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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tations and the foundation for new knowledge generation. In this instance, however, expectations gained from knowing the past prevented the experts, or at least most of them, from seeing that something different was really happening; these experts failed the vision test—to match what was known with what was happening and see both similarities and differences. That difference from previous outbreaks lay in the habitual movement of people across the porous borders where Guinea, Liberia, and Sierra Leone abut one another, as the roads and available transportation made it easy for people to travel to the larger towns and the capital cities and on to nearby countries in the region—and, in a few instances, bringing the virus with them. That was all it took, and this ability transformed what had always been a short, limited outbreak in the past, to an epidemic spiraling out of control; this was especially true where the epidemic had originally begun, where it was rapidly becoming a major public health disaster, quickly outpacing the limited health and public health systems and overwhelming any surge capacity there was. Although the global humanitarian organization Médecins Sans Frontières (MSF) became involved early on, its capacity too was quickly overwhelmed by the magnitude of the outbreak. While MSF recognized what was happening, its calls for urgent international action were essentially disregarded, in part because of the reluctance of the affected countries to admit there was a crisis and, in turn, the reluctance of the World Health Organization (WHO) to believe this was really different, making WHO unable to focus more on global public health than on politics and take the necessary action only it could take.

The rest is now history: an outbreak of unprecedented magnitude in a setting of limited capacity, with political systems that were fragile after many years of civil war, plagued by violence, and the virus itself that killed health care workers, further decimating the indigenous capacity to care for patients and limit further dissemination of infection. It was a perfect storm. On top of this, there was a sluggish and contentious international emergency response, especially early on, often carried out with overworked, well-intentioned but relatively untrained international volunteer health workers. When the almost inevitable instances of infection occurred among them, they were repatriated to their countries of origin for state-of-the-art supportive clinical care, often raising the fear levels about the importation of Ebola among the general public in the United States and other developed countries. Some of these individuals received experimental drugs that were being slowly advanced through preclinical research in their countries, and when they survived it fanned the rumors circulating in the affected West African countries of a magic serum that cured the expatriates but that was not being made available to the local African population. This fed into conspiracy theories about the origin of the virus, and when there was the possibility of actually doing clinical research to establish safety and efficacy

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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of drugs and vaccines for Ebola, the conspiracy morphed into the view that now the West was using Africans as guinea pigs to study these experimental products. To make it worse, the various groups capable of mounting and overseeing these clinical trials could not agree on the right study design, the ethics of using controls and randomization, or whose patients would be offered the opportunity to be enrolled. With this background it is not surprising there was community backlash against the health care workers, the proposed studies, the health and political leadership in the countries, and the researchers, both local and international.

The challenge this committee has taken on is to step back and review the clinical research conducted during 2014–2015, specifically in Guinea, Liberia, and Sierra Leone, to better understand what happened, the nature of the constraints that affected the design and implementation of human clinical trials, and what knowledge was actually gained on the safety and efficacy of the tested drugs and vaccines, most of which had never been given to a human before. All of this took place in the setting of an exploding humanitarian disaster where the provision of effective baseline clinical care was beyond the reach of many of the emergency treatment centers that were ultimately set up, at least in the early months of the outbreak, and where both caregivers and researchers would be constrained by the personal protective equipment they had to use and the limited time they could spend at the bedside, given the ambient conditions. And so in February 2016 we were asked by the National Academies of Sciences, Engineering, and Medicine to co-chair a committee that would make recommendations to the three U.S. sponsors, the Office of the Assistant Secretary for Preparedness and Response, the National Institute of Allergy and Infectious Disease, and the U.S. Food and Drug Administration of the U.S. Department of Health and Human Services, to help them to do better the next time an outbreak like this occurs. The specific charge we took on is presented in Chapter 1, and the rest of the report presents our findings, conclusions, and recommendations to the study sponsors and, beyond them, to the greater global community. Our goal was not to cast blame but rather to find ways to improve what should be done the next time.

However, the statement of task was cognizant of the fact that conducting clinical trials requires “collaborative investment to achieve long-term ethical and scientific gains” and “planning activities during the inter-epidemic period.” To effectively launch trials in the context with which they were carried out during the Ebola outbreak, multiple issues of a scientific, political, cultural, social, ethical, and economic nature impacted the clinical research agenda and what it could produce; and there were both national and international implications that required consideration. We watched the efforts to build capacity in the three epicenter countries with support from the United States (and many other international donors and

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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scientific institutions) and then saw funds allocated to this effort by the U.S. Congress tapped to meet the new challenge of Zika virus, the outbreak du jour, before the local and global benefits of the investments in Ebola, those undertaken and those planned and still unfolding, could be reaped for the global community, not the least of which for the United States as well. While we do not provide specific recommendations regarding the sources of the necessary investments to build a better global system to address emerging infectious diseases in the future, we do address what we believe to be the critical issues to tackle and some of the actions necessary to do that. But we also know that funding will determine how far the world can improve on the status of things as they were in January 2014, when the Ebola outbreak in West Africa began, and how quickly that improvement might happen. It is clear that preparedness to respond to the next outbreak and preparedness to pursue clinical research on therapeutic products and vaccines during an outbreak are of the highest priority and that they will require sustained and flexible funding sources, free from political whim and pressure, to develop and reach the necessary functionality. We note here new efforts by the World Bank Group to engage with the WHO and its newfound partners, including the Food and Agriculture Organisation, the World Organization for Animal Health, and a number of United Nations agencies. And we welcome the growing engagement of these key players with foundations and charities to consult and collaborate more effectively on emerging infectious diseases, and to identify what needs to be done and how to find the resources from the global community to make that happen today and in the future.

The costs for the U.S. government and its many partners around the world to respond to the epidemic were enormous, as were the costs borne by the three affected countries. The economic effects of the epidemic outbreak will be felt for many years to come in Guinea, Liberia, and Sierra Leone. It seems amazing that despite the 40-year head start that we had for Ebola we were not adequately prepared and that nearly 12,000 deaths later we still do not have licensed therapeutic agents or vaccines. Rather than expecting that the swarm of wealthy, powerful, and knowledgeable experts would rapidly develop and implement effective plans to control the epidemic, we learned that community engagement takes time and skill to reach common ground on what needs to be done, that communication science requires considerable investment, and that strengthening capacity in clinical care, public health, and health research systems is now an urgent and necessary requirement if this sort of epidemic is to be prevented and controlled in the future. The global costs of failure are devastating; the price of effective preparedness is certainly worth the investment. Many highly motivated individuals and institutions can turn this Ebola outbreak into a

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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global good, if they are charged with implementing the international learnings from the experience.

What we do not know is whether the needs, both in terms of capacity strengthening and the requisite financial support, can be met by an often fragmented global system of governance and engagement. We thank the brave people of Guinea, Liberia, and Sierra Leone, who persevered through the ordeal and have emerged more committed than ever to the success of their countries, and all of those who attended the open meetings of the committee and gave us the benefit of their knowledge, experience, and passion to help in every way they could to improve the response to such a calamity in the future—and perhaps to be able to prevent such outbreaks. This is the intent of this report, to move the dial forward to reach such a day. As we look back at the work by a remarkable group of committee members, our consultant Janet Darbyshire, and our project staff at the National Academies of Sciences, Engineering, and Medicine with whom we worked so closely over the past 10 months, we can identify one rather critical feature of a global community we know and believe in: from those who have much, much is expected.

Gerald T. Keusch and Keith McAdam, Co-Chairs
Committee on Clinical Trials During the 2014–2015 Ebola Outbreak

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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Acknowledgments

This report reflects contributions from a number of individuals and groups. The committee takes this opportunity to recognize those who so generously gave their time and expertise to inform its deliberations. To begin the committee would like to thank the individuals who attended and presented at their open-session meetings (see Appendix A). The committee greatly benefited from the opportunity for discussion with these individuals and is thankful for their many contributions.

The committee could not have done its work without the support of the many clinical trial teams who surmounted innumerable challenges to successfully conduct clinical trials in the midst of an unprecedented outbreak, specifically Ebola ça Suffit (Ana Maria Henao-Restrepo, Initiative for Vaccine Research and World Health Organization; Mandy Kader Konde, University of Conakry, Guinea Ebola Research Commission, and Center of Research on Diseases), STRIVE (Anne Schuchat, Centers for Disease Control and Prevention; Barbara Mahon, Centers for Disease Control and Prevention; Mohamed Samai, College of Medicine and Allied Health Sciences and Ministry of Health and Sanitation, Freetown, Sierra Leone), EBOVAC–Salone (Johan Van Hoof, Janssen Pharmaceuticals R&D; Christopher McShane, Janssen Research & Development, LLC), PREVAIL (Richard T. Davey, National Institutes of Allergy and Infectious Diseases [NIAID], National Institutes of Health [NIH]; John Beigel, Leidos Biomedical Research, Inc., in support of Clinical Research Section, Liberian Institute of Biomedical Research, NIAID, NIH; Mike Proschan, NIAID, NIH; Lori Dodd, NIAID, NIH; Jerome F. Pierson, NIAID, NIH; James Neaton, University of Minnesota; Stephen B. Kennedy, Incident Manage-

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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ment System, Liberia; Barthalomew Wilson, Partnership for Research on Ebola Virus in Liberia), JIKI (France Mentre, Université Paris Diderot, Paris, France; Denis Malvy, University Hospital of Bordeaux; Abdoul Habib Beavogui, National Center for Training and Research in Rural Health “Jean SENECAL” of Maferinyah, Republic of Guinea), RAPIDE–Ebola (Trudie Lang, University of Oxford; John Whitehead, Lancaster University; Peter Horby, University of Oxford and International Severe Acute Respiratory and Emerging Infections Consortium), and Ebola-Tx (Johan van Griensven, Institute of Tropical Medicine–Antwerp).

The committee is grateful to the people of Guinea, Liberia, and Sierra Leone for hosting us and generously sharing their expertise, experiences, and personal stories. In particular, we would like to thank the representatives of the ministries of health Hon. Zulianatu Cooper (Sierra Leone), Hon. Alie Wurie (Sierra Leone), Hon. Yah Zolia (Liberia), and Hon. Tolbert Nyenswah (Liberia). Special thanks to Ambassador Juli Endee (Liberia Crusaders for Peace) and Chief Zanzan Kawa (Council of Chiefs of Liberia) for graciously welcoming us to Liberia and sharing with us the stories of their communities. We also thank Mosoka Fallah (Action Contre la Faim), Vuyu Kanda Golakai (University of Liberia), and Fatorma Bolay (Liberia Institute of Biomedical Research) for their assistance in arranging on-site visits and providing the committee the opportunity to experience Monrovia.

Many others provided support to this project in various ways. We thank Alexander M. Capron, University of Southern California, for his thoughtful review. We are grateful to Dana Vigue for her research assistance and to Elena Ovaitt Weiss for her creative efforts in our graphic design process, and finally, Robert Pool is to be recognized for his editorial assistance in preparing this report.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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1-1 Weekly reported Ebola cases during the 2014–2015 Ebola outbreak

3-1 Clinical trial enrollment dates during the 2014–2015 Ebola outbreak—therapeutic trials

4-1 Clinical trial enrollment start dates during the 2014–2015 Ebola outbreak—vaccine trials

4-2 Timeline of PREVAIL Trial

5-1 Timeline to implement a clinical trial

6-1 Organizational structure of the Liberian–U.S. research partnership

7-1 A timeline of critical components: Launching clinical trials in an epidemic

7-2 A visual representation of how the international coalition of stakeholders and rapid research response workgroup relate to one another, as suggested in Recommendations 7a and 7b

TABLES

S-1 Investigational Ebola Therapeutic Agents in Formal Clinical Trials During the 2014–2015 Ebola Outbreak

S-2 Investigational Ebola Vaccines in Formal Clinical Trials During the 2014–2015 Ebola Outbreak

1-1 Data Depicting the Deficit of Medical Doctors and Hospital Beds in the Ebola-Affected Countries at the Time of the Ebola Outbreak in Comparison to Higher-Income Countries

3-1 Timeline of Therapeutic Trials

3-2 Available Data on Investigational Therapeutic Agents for Ebola When Trials Were Being Planned (November 2014)

3-3 Summary of Therapeutic Trials Conducted During 2014–2015 Ebola Outbreak

4-1 October 2015 WHO Summary of the Phase 1 Ebola Vaccine Trials

4-2 Timeline of Vaccine Trials

4-3 Calculations of Vaccine Efficacy and Vaccine Effectiveness Based on Different Study Populations—Guinea Ring Vaccine Trial

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Acronyms and Abbreviations

Ad26

recombinant adenovirus serotype 26

AIDS

acquired immune deficiency syndrome

ASPR

Office of the Assistant Secretary for Preparedness and Response

AZT

azidothymidine, also known as Zidovudine (ZDV)

BBC

British Broadcasting Corporation

CCC

community care center

CDC

U.S. Centers for Disease Control and Prevention

CEPI

Coalition for Epidemic Preparedness Innovations

ChAd3

recombinant chimpanzee adenovirus type 3 vector vaccine

CIOMS

Council for International Organizations of Medical Sciences

CMV

cytomegalovirus

COE

Council of Europe

COHRED

Council on Health Research for Development

CP

convalescent plasma

Ct

cycle threshold (PCR)

DNA

deoxyribonucleic acid

DSMB

data and safety monitoring board

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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EBOVAC

Ebola vaccine projects

EC50

half maxima effective concentration

ECOWAS

Economic Community of West African States

ELISA

enzyme-linked immunosorbent assay

ENHR

essential national health research

ETU

Ebola treatment unit

EVD

Ebola virus disease

FDA

U.S. Food and Drug Administration

GCP

good clinical practice

GDP

gross domestic product

GHSA

Global Health Security Agenda

GP

glycoprotein

GSK

GlaxoSmithKline

H1N1

influenza A virus subtype H1N1

HCW

health care worker

HHS

U.S. Department of Health and Human Services

HIV

human immunodeficiency virus

IC50

half maximal inhibitory concentration

ICS

international coalition of stakeholders

IDA

International Development Association component of the World Bank Group

IDSR

integrated disease surveillance and response

IgG

immunoglobulin-G

IHR

International Health Regulations

IMC

International Medical Corps

Inserm

Institut national de la santé et de la recherche médicale (French National Institute of Health and Medical Research)

IOM

Institute of Medicine

IV

intravenous

JIKI

means “Hope” in “Kissi” language

LIBR

Liberian Institute of Biomedical Research

MERS-CoV

Middle East respiratory syndrome coronavirus

MOU

memorandum of understanding

MSF

Médecins Sans Frontières (Doctors Without Borders)

MVA

modified vaccinia virus

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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NGO

nongovernmental organization

NHP

nonhuman primate

NIAID

National Institute of Allergy and Infectious Diseases, NIH

NIH

U.S. National Institutes of Health

oSOC

optimized standard of care

PCR

polymerase chain reaction

PEF

Pandemic Emergency Financing Facility

PHEIC

public health emergencies of international concern

PK

pharmacokinetics

PO

per os (oral administration)

PPE

personal protective equipment

PREVAIL

Partnership for Research on Ebola Virus in Liberia, NIH

R3W

rapid research response workgroup

R&D

research and development

RAPIDE

Rapid Assessment of Potential Interventions & Drugs for Ebola

RCT

randomized controlled trial

REDISSE

Regional Disease Surveillance Systems Enhancement Program

RHInnO

Rapid Health Innovation

RNA

ribonucleic acid

rVSV

recombinant vesicular stomatitis virus

SAE

serious adverse event

SARS

severe acute respiratory syndrome

SBCC

social and behavior change communication

SOC

standard of care

STAC-EE

Scientific and Technical Advisory Committee on Ebola Experimental Interventions

STRIVE

Sierra Leone Trial to Introduce a Vaccine against Ebola, CDC

TB

tuberculosis

UN

United Nations

UNESCO

United Nations Educational, Scientific and Cultural Organization

USAID

U.S. Agency for International Development

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
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WAHO

West African Health Organization

WHO

World Health Organization

WMA

World Medical Association

ZEBOV

Zaire Ebola virus

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Integrating Clinical Research into Epidemic Response: The Ebola Experience Get This Book
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The 2014–2015 Ebola epidemic in western Africa was the longest and most deadly Ebola epidemic in history, resulting in 28,616 cases and 11,310 deaths in Guinea, Liberia, and Sierra Leone. The Ebola virus has been known since 1976, when two separate outbreaks were identified in the Democratic Republic of Congo (then Zaire) and South Sudan (then Sudan). However, because all Ebola outbreaks prior to that in West Africa in 2014–2015 were relatively isolated and of short duration, little was known about how to best manage patients to improve survival, and there were no approved therapeutics or vaccines. When the World Heath Organization declared the 2014-2015 epidemic a public health emergency of international concern in August 2014, several teams began conducting formal clinical trials in the Ebola affected countries during the outbreak.

Integrating Clinical Research into Epidemic Response: The Ebola Experience assesses the value of the clinical trials held during the 2014–2015 epidemic and makes recommendations about how the conduct of trials could be improved in the context of a future international emerging or re-emerging infectious disease events.

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