WHO report: Placebo use in vaccine trials: Recommendations of a WHO expert panel
Annette Rida, Abha Saxenab, Abdhullah H. Baquic, Anant Bhand, Julie Binese, Marie-Charlotte Bouesseauf, Arthur Caplang, James Colgroveh, Ames Dhaii, Rita Gomez-Diazj, Shane K. Greenk,
Gagandeep Kangl, Rosanna Lagosm, Patricia Lohn, Alex John Londono, Kim Mulhollandp,
Pieter Neelsq, Punee Pitisuttithumr, Samba Cor Sarrs, Michael Selgelidt, Mark Sheehanu, Peter G. Smithv
Vaccine – Available online 25 April 2014
In Press, Corrected Proof — Note to users
Open Access – Under a Creative Commons license
Placebo controls may be acceptable even when an efficacious vaccine exists, in the following four possible situations:
:: When developing a locally affordable vaccine.
:: When evaluating the local safety and efficacy of an existing vaccine.
:: When testing a new vaccine when an existing vaccine is not considered appropriate locally.
:: When determining the local burden of disease.
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.