Placebo use in vaccine trials: recommendations of a WHO expert panel

Annette Rid¹, Abha Saxena², Abdhullah H Baqui³, Anant Bhan⁴, Julie Bines⁵, Marie-Charlotte Bouesseau⁶, Arthur Caplan⁷, James Colgrove⁸, Ames Dhai⁹, Rita Gomez-Diaz¹⁰, Shane K Green¹¹, Gagandeep Kang¹², Rosanna Lagos¹³, Patricia Loh¹⁴, Alex John London¹⁵, Kim Mulholland¹⁶, Pieter Neels¹⁷, Punee Pitisuttithum¹⁸, Samba Cor Sarr¹⁹, Michael Selgelid²⁰, Mark Sheehan²¹, Peter G Smith²²

Affiliations

¹ Department of Social Science, Health & Medicine, King's College London, Strand, London WC2R 2LS, United Kingdom. Electronic address: annette.rid@kcl.ac.uk.
² Knowledge, Ethics and Research, World Health Organization, Geneva, Switzerland.
³ International Center for Maternal and Newborn Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
⁴ Ethical, Social and Cultural Program for Global Health, University of Toronto, Toronto, ON, Canada.
⁵ Murdoch Childrens Research Institute, University of Melbourne, Parkville, VIC, Australia.
⁶ Service Delivery and Safety, World Health Organization, Geneva, Switzerland.
⁷ Division of Medical Ethics, NYU School of Medicine, New York, NY, United States.
⁸ Mailman School of Public Health, Columbia University, New York, NY, United States.
⁹ Steve Biko Centre for Bioethics, University of Witwatersrand, Johannesburg, South Africa.
¹⁰ Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Ciudad de Mexico, D.F., Mexico.
¹¹ Ethical, Social and Cultural Program for Global Health, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada.
¹² Christian Medical College, Vellore, Tamil Nadu, India.
¹³ Hospital de Niños Roberto del Río, Santiago de Chile, Chile.
¹⁴ Melbourne Law School, University of Melbourne, Carlton, VIC, Australia.
¹⁵ Department of Philosophy, Carnegie Mellon University, Pittsburgh, PA, United States.
¹⁶ London School of Hygiene and Tropical Medicine, London, United Kingdom.
¹⁷ Vaccine Advice BVBA, Zoersel, Belgium.
¹⁸ Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
¹⁹ Ministry of Health and Social Action 1, Dakar-Fann, Senegal.
²⁰ Centre for Human Bioethics, Monash University, Monash, VIC, Australia.
²¹ The Ethox Centre, University of Oxford, Oxford, United Kingdom.
²² Medical Research Council (MRC) Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.

PMID: 24768580
PMCID: PMC4157320
DOI: 10.1016/j.vaccine.2014.04.022

Placebo use in vaccine trials: recommendations of a WHO expert panel

Annette Rid et al. Vaccine. 2014.

. 2014 Aug 20;32(37):4708-12.

doi: 10.1016/j.vaccine.2014.04.022. Epub 2014 Apr 25.

Authors

Affiliations

¹ Department of Social Science, Health & Medicine, King's College London, Strand, London WC2R 2LS, United Kingdom. Electronic address: annette.rid@kcl.ac.uk.
² Knowledge, Ethics and Research, World Health Organization, Geneva, Switzerland.
³ International Center for Maternal and Newborn Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
⁴ Ethical, Social and Cultural Program for Global Health, University of Toronto, Toronto, ON, Canada.
⁵ Murdoch Childrens Research Institute, University of Melbourne, Parkville, VIC, Australia.
⁶ Service Delivery and Safety, World Health Organization, Geneva, Switzerland.
⁷ Division of Medical Ethics, NYU School of Medicine, New York, NY, United States.
⁸ Mailman School of Public Health, Columbia University, New York, NY, United States.
⁹ Steve Biko Centre for Bioethics, University of Witwatersrand, Johannesburg, South Africa.
¹⁰ Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Ciudad de Mexico, D.F., Mexico.
¹¹ Ethical, Social and Cultural Program for Global Health, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada.
¹² Christian Medical College, Vellore, Tamil Nadu, India.
¹³ Hospital de Niños Roberto del Río, Santiago de Chile, Chile.
¹⁴ Melbourne Law School, University of Melbourne, Carlton, VIC, Australia.
¹⁵ Department of Philosophy, Carnegie Mellon University, Pittsburgh, PA, United States.
¹⁶ London School of Hygiene and Tropical Medicine, London, United Kingdom.
¹⁷ Vaccine Advice BVBA, Zoersel, Belgium.
¹⁸ Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
¹⁹ Ministry of Health and Social Action 1, Dakar-Fann, Senegal.
²⁰ Centre for Human Bioethics, Monash University, Monash, VIC, Australia.
²¹ The Ethox Centre, University of Oxford, Oxford, United Kingdom.
²² Medical Research Council (MRC) Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.

PMID: 24768580
PMCID: PMC4157320
DOI: 10.1016/j.vaccine.2014.04.022

Abstract

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.

Keywords: Ethics; International research; Placebo controls; Risk; Trial design; Vaccine trials.

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Comment in

Placebo use in vaccine trials: Caution when using active vaccines as placebo.
Byberg S, Benn CS. Byberg S, et al. Vaccine. 2017 Mar 1;35(9):1211. doi: 10.1016/j.vaccine.2015.03.024. Epub 2015 Mar 21. Vaccine. 2017. PMID: 25804705 No abstract available.

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Placebo use in vaccine trials: recommendations of a WHO expert panel

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Placebo use in vaccine trials: recommendations of a WHO expert panel

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