title: The design and analysis of cholera vaccine trials: recent lessons from Bangladesh.
abstract: The recent spread of cholera to Latin America, together with the persistent burden of this 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 is well established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the setting 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 El Tor cholera.
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh.
authors.forename: J
authors.initials: J
authors.lastname: Clemens
authors.forename: D
authors.initials: D
authors.lastname: Sack
authors.forename: M
authors.initials: M
authors.lastname: Rao
authors.forename: J
authors.initials: J
authors.lastname: Chakraborty
authors.forename: B
authors.initials: B
authors.lastname: Kay
authors.forename: F
authors.initials: F
authors.lastname: Ahmed
authors.forename: M R
authors.initials: MR
authors.lastname: Khan
authors.forename: F P
authors.initials: FP
authors.lastname: van Loon
authors.forename: A M
authors.initials: AM
authors.lastname: Svennerholm
authors.forename: J
authors.initials: J
authors.lastname: Holmgren
mesh_terms: D000017:ABO Blood-Group System; D000367:Age Factors; D001459:Bangladesh / Q000453:epidemiology; D002675:Child, Preschool; D002771:Cholera / Q000097:blood / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000592:standards*; D002986:Clinical Trials as Topic / Q000592:standards*; D004812:Epidemiologic Methods; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D015994:Incidence; D007223:Infant; D011159:Population Surveillance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012107:Research Design / Q000592:standards*; D012307:Risk Factors; D015983:Selection Bias; D012703:Serotyping; D016896:Treatment Outcome; D014734:Vibrio cholerae / Q000145:classification
chemical_list: D000017:ABO Blood-Group System; D022121:Cholera Vaccines