Placebo use in vaccine trials: recommendations of a WHO expert panel.
Vaccines are among the most cost-effective interventions against infectious diseases. Many candidate vaccines targeting neglected diseases in low- and middle-income countries are now progressing to large-scale clinical testing. However, controversy surrounds the appropriate design of vaccine trials and, in particular, the use of unvaccinated controls (with or without placebo) when an efficacious vaccine already exists. This paper specifies four situations in which placebo use may be acceptable, provided that the study question cannot be answered in an active-controlled trial design; the risks of delaying or foregoing an efficacious vaccine are mitigated; the risks of using a placebo control are justified by the social and public health value of the research; and the research is responsive to local health needs. The four situations are: (1) developing a locally affordable vaccine, (2) evaluating the local safety and efficacy of an existing vaccine, (3) testing a new vaccine when an existing vaccine is considered inappropriate for local use (e.g. based on epidemiologic or demographic factors), and (4) determining the local burden of disease.
Department of Social Science, Health & Medicine, King's College London, Strand, London WC2R 2LS, United Kingdom. Electronic address: annette.rid@kcl.ac.uk.
Annette
A
Rid
Knowledge, Ethics and Research, World Health Organization, Geneva, Switzerland.
Abha
A
Saxena
International Center for Maternal and Newborn Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Abdhullah H
AH
Baqui
Ethical, Social and Cultural Program for Global Health, University of Toronto, Toronto, ON, Canada.
Anant
A
Bhan
Murdoch Childrens Research Institute, University of Melbourne, Parkville, VIC, Australia.
Julie
J
Bines
Service Delivery and Safety, World Health Organization, Geneva, Switzerland.
Marie-Charlotte
MC
Bouesseau
Division of Medical Ethics, NYU School of Medicine, New York, NY, United States.
Arthur
A
Caplan
Mailman School of Public Health, Columbia University, New York, NY, United States.
James
J
Colgrove
Steve Biko Centre for Bioethics, University of Witwatersrand, Johannesburg, South Africa.
Ames
A
Dhai
Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Ciudad de Mexico, D.F., Mexico.
Rita
R
Gomez-Diaz
Ethical, Social and Cultural Program for Global Health, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada.
Shane K
SK
Green
Christian Medical College, Vellore, Tamil Nadu, India.
Gagandeep
G
Kang
Hospital de Niños Roberto del Río, Santiago de Chile, Chile.
Rosanna
R
Lagos
Melbourne Law School, University of Melbourne, Carlton, VIC, Australia.
Patricia
P
Loh
Department of Philosophy, Carnegie Mellon University, Pittsburgh, PA, United States.
Alex John
AJ
London
London School of Hygiene and Tropical Medicine, London, United Kingdom.
Kim
K
Mulholland
Vaccine Advice BVBA, Zoersel, Belgium.
Pieter
P
Neels
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Punee
P
Pitisuttithum
Ministry of Health and Social Action 1, Dakar-Fann, Senegal.
Samba Cor
SC
Sarr
Centre for Human Bioethics, Monash University, Monash, VIC, Australia.
Michael
M
Selgelid
The Ethox Centre, University of Oxford, Oxford, United Kingdom.
Mark
M
Sheehan
Medical Research Council (MRC) Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Peter G
PG
Smith
D017408:Guidelines as Topic; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000941:ethics*; D012107:Research Design; D014612:Vaccines; D014944:World Health Organization
D010919:Placebos; D014612:Vaccines
Ethics; International research; Placebo controls; Risk; Trial design; Vaccine trials