Ebola: Experts support a varied approach to Ebola trials
In a letter to the Wall Street Journal today, 19 experts from Africa, Asia, Europe and the US set out their support for the use of a range of clinical trial designs during the Ebola epidemic. The letter responds to an article published in the Wall Street Journal on 13 May, which called into question the ethics of conducting single-arm clinical trials during the outbreak in Guinea, Liberia and Sierra Leone. Signatories include representatives from the World Health Organisation (WHO), Médecins Sans Frontières (Doctors Without Borders), Nigerian National Health Research Ethics Committee, University of Oxford and the Wellcome Trust’s Director Dr Jeremy Farrar. An edited version of the letter appeared in the paper on 26 May. You can read the full text of the letter and list of signatories below.
We believe the article “Disputes Emerge on African Ebola Drug Trials” (World News, May 13) ignores the complexity of the issues surrounding the use and evaluation of experimental drugs in epidemics such as Ebola. We are writing on behalf of 19 experts from Africa, Asia, Europe and the U.S., representing research institutions, ethics committees, the World Health Organisation, Doctors Without Borders and the Wellcome Trust.
The ethics of evaluating novel treatments and vaccines in the midst of this humanitarian crisis have been considered widely and in depth, rightly taking into account the societal and operational conditions that existed at the height of the epidemic and the very high mortality rates in this infection.
The legitimacy and value of different methodological approaches, including both placebo controlled and single-arm studies, have been fully endorsed by national authorities in the affected countries, healthcare givers, non-governmental organizations, multiple ethics committees, world experts in the Strategic Advisory Committee on Ebola Experimental Interventions, convened by the World Health Organization, and by the Presidential Commission for the Study of Bioethical Issues.
It is false to assert that single-arm trials could not be done in the US or the UK. Single-arm trials with clear methodologies and safeguards are used widely in medical research, particularly for early assessment of new cancer drugs, and they generate useful, interpretable data. Treatment recommendations and marketing authorizations granted by both US and European regulatory agencies have been based on such studies.
Lastly, and worryingly, the article suggests that the brincidofovir trial was terminated because of patient outcomes. This is not the case. The trial collapsed when Chimerix, the manufacturer, withdrew its support, which, combined with the end of the epidemic in Liberia, left the Trial Steering Committee no option but to terminate.
Given the severity of the infection and the seriousness of the humanitarian disaster that Ebola has caused, it is essential to foster a balanced, informed and non-adversarial debate on these issues. The scientific community must find ways to conduct essential trials and share their results swiftly, ethically and without controversy when inevitable future outbreaks arise.
Professor Clement Adebamowo, University of Maryland and Nigerian National Health Research Ethics Committee
Dr Annick Antierens, Médecins Sans Frontières (Doctors Without Borders)
Professor Fred Binka, University of Health and Allied Sciences, Ho, Ghana
Professor Roberto Bruzzone, HKU-Pasteur Research Pole
Professor Arthur Caplan, Division of Medical Ethics, NYU Langone Medical Center’s Department of Population Health
Professor Jean-Francois Delfraissy, INSERM
Dr Bertrand Draguez, Médecins Sans Frontières (Doctors Without Borders)
Dr Jeremy Farrar, Wellcome Trust
Professor David Heymann, Chatham House
Professor Peter Horby, University of Oxford
Professor Pontiano Kaleebu, MRC/UVRI Uganda Research Unit on AIDS
Dr Marie-Paule Kieny, World Health Organisation
Professor Jean-Jacques Muyembe-Tamfum, Kinshasa University Medical school and The National Institute for Biomedical Research, Kinshasa
Dr Piero Olliaro, TDR, the Special Programme for Research and Training in Tropical Diseases at the World Health Organisation
Professor Peter Piot, London School of Hygiene & Tropical Medicine
Dr Sani Sesay, West African Task Force for the Control of Emerging and Re-emerging Infectious Diseases (WATER)
Dr Aissatou Toure, Institut Pasteur Dakar
Professor Nick White, Mahidol University, Bangkok
Professor John Whitehead, Department of Mathematics and Statistics at Lancaster University