Annette RidAbha SaxenaAbdhullah H. BaquiAnant BhanJulie BinesMarie Charlotte BouesseauArthur CaplanJames ColgroveAmes DhaiRita Gomez-DiazShane K. GreenGagandeep KangRosanna LagosPatricia LohAlex John LondonKim MulhollandPieter NeelsPunee PitisuttithumSamba Cor SarrMichael SelgelidMark SheehanPeter G. SmithKing's College LondonOrganisation Mondiale de la SanteJohns Hopkins Bloomberg School of Public HealthUniversity of TorontoUniversity of MelbourneNYU School of MedicineColumbia University Medical CenterUniversity of the Witwatersrand, Faculty of Health SciencesInstituto Mexicano del Seguro SocialSaint Michael's Hospital University of TorontoChristian Medical College, VelloreHospital de Ninos Robeto del RioMelbourne Law SchoolCarnegie Mellon UniversityLondon School of Hygiene & Tropical MedicineVaccine Advice BVBAMahidol UniversityMinistry of Health and Social Action 1Monash UniversityUniversity of Oxford2018-11-092018-11-092014-08-20Vaccine. Vol.32, No.37 (2014), 4708-4712187325180264410X2-s2.0-84905221885https://repository.li.mahidol.ac.th/handle/20.500.14594/33231Vaccines 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. © 2014 The Authors.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineVeterinaryNoteSCOPUS10.1016/j.vaccine.2014.04.022