Guidelines for clinical trials of dengue vaccine in endemic areas

Guidelines for the clinical evaluation of dengue vaccines in endemic areas have recently been developed, building upon earlier recommendations published in 2002 (WHO. 2002. Guidelines for the evaluation of dengue vaccines in populations exposed to natural infection. Geneva, Switzerland. Report no. TDR/IVR/DEN/02.1). This new document discusses the rationale and background of dengue vaccine trials and outlines dengue case definitions, proposed efficacy end points, requirements for trial sites, methods of measurement and proposed safety schedules. Demonstrated protective efficacy against each of the four dengue virus serotypes without safety concerns is the objective of any candidate tetravalent vaccine clinical trial. Accurate epidemiological data of dengue and other circulating flaviviruses over multiple transmission seasons are required to address factors such as background flavivirus immunity and subclinical infections that may confound serological results. Furthermore, bridging and post-licensure studies may be necessary to extend conclusions concerning vaccine characteristics, while co-administration trials are necessary in paediatrics. These guidelines are primarily aimed at national regulatory authorities, vaccine developers and research scientists and should be analysed, discussed and adjusted where necessary.