© 1993 Oxford University Press
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The Design and Analysis of Cholera Vaccine Trials: Recent Lessons from Bangladesh
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* International Cetre for Diarrhoea1 Disease Research Bangladesh
** National Institute of Child Health and Human Development Bethesda, USA
Johns Hopkins University School of Public Health Baltimore, USA
§ Centers for Disease Control Atlanta, USA
University of Goteborg Gotcborg, Sweden
Reprint requests to: Dr J Clemens. Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, G100 Executivc Blvd., Berhesda, MD 20892. USA
The recent spread of cholera to Latin America, tcgether with the persistent burden of thia disease in Asia and Africa, have stimulated efforts to evaluate new cholera vaccines in field settings. Although the standard experimental paradigm for vaccine field trials iswell established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the settings under study. Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable, multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial. They also underscore how the filtering effect of enrolling subjects into a prospective trial can dramatically reduce the available population for study, and can yield a study sample whose expected risk of cholera differs markedly from that for the source population. Finally, the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy, and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups, and in subjects exposed to classical versus EI Tor cholera.
Revised 1 December 1992