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 placebo controls when an efficacious vaccine already exists.
The WHO Department of Ethics and Social Determinants convened an expert consultation to provide recommendations on the use of placebo controls in vaccine trials in cases where an efficacious vaccine already exists. The focus was on large-scale clinical trials that test vaccines in Phases III and IV of development (i.e. where preliminary testing of safety and immunogenicity, and sometimes efficacy, has been completed in Phase I and II trials). The panel, consisting of 20 experts from 11 countries, met to discuss relevant issues and develop recommendations in consultation with key stakeholders in international vaccine research. The present paper develops the discussion and conclusions from that meeting
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.
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