WHO: Expert consultation on the use of placebos in vaccine trials.
November 2013
ISBN 978 92 4 150625 0 (NLM classification: QW 805)

The Expert Consultation on the Use of Placebos in Vaccine Trials was convened by the World Health Organization (WHO) in Annecy, France on 17–18 January 2013 under the overall guidance of Rüdiger Krech, WHO Director of the Department of Ethics and Social Determinants, and Marie-Paule Kieny, Assistant Director-General, Health Systems and Innovation.

Excerpt
Conclusion
The use of placebos in a vaccine clinical trial when there is already an effective or partially effective vaccine raises challenging ethical questions. National and international documents on research involving human subjects have set forth valuable guidelines on the circumstances in which use of placebos is ethically acceptable in a randomized controlled trial. However, none of these documents specifically addresses the use of placebos in vaccine trials. The purpose of the expert consultation described in this report was to address the ethical ambiguity in this area and formulate concrete and practical guidance for action. The critical need to develop new and improved vaccines, especially for use in LMICs that bear the heaviest disease burden, provided the impetus for this consultation and the resulting recommendations.

This report presents a typology of cases in which the use of placebos in vaccine clinical trials may be justified, and offers procedural and substantive recommendations to help trial sponsors and researchers, policy-makers, RECs, and other stakeholders evaluate proposed trial designs. The report specifies five situations in which placebos may be ethically acceptable even in the presence of an efficacious vaccine. In these situations, it is recommended that there be ongoing consultation between trial sponsors and host country actors, thorough assessment of and communication about risks, and consideration of alternative trial designs.

Researchers should consider whether risks associated with the use of placebos can be adequately mitigated, and research protocols should explain the scientific necessity and social and public health value of a placebo design. Researchers should also undertake activities to mitigate risks related to the use of placebos. Additionally, the post-trial availability of the vaccine in the trial country should be carefully examined.

This document is not intended to suggest a definitive course of action for all vaccine trials when an effective or partially effective vaccine already exists. Rather, the recommendations set forth here are designed to provide an analytic framework to aid decision-making. Participants at the expert consultation agreed that the ultimate judgement about the use of placebos in these cases will depend on the specifics of the trial vaccine and the circumstances of the country in which the trial will be conducted. A careful weighing of numerous considerations by stakeholders will therefore be required. The overarching goal of these recommendations is two-fold: to assure that participants in vaccine clinical trials are protected from unjustifiable risks, and to facilitate the conduct of beneficial and urgently needed vaccine research. WHO encourages ongoing discussion of these issues and welcomes feedback on the guidance provided here.