Guidance on the evaluation of Plasmodium vivax vaccines in populations exposed to natural infection.

In this paper we give guidance for the design and conduct of vaccine trials against Plasmodium vivax malaria. The paper supplements earlier guidelines on the planning of vaccine trials against Plasmodium falciparum malaria [WHO. Guidelines for the evaluation of Plasmodium falciparum vaccines in populations exposed to natural infections. Geneva: World Health Organization; 1997, http://www.who.int/vaccine_research/feuill_1_4-2.pdf], with further considerations in two later documents [Moorthy VS, Reed Z, Smith PG. Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation. Vaccine 2007 July 9;25(28):5115-23; Moorthy V, Reed Z, Smith P. MALVAC 2008: measures of efficacy of malaria vaccines in phase 2b and phase 3 trials - scientific, regulatory and public health perspectives. Vaccine 2009 January 29;27(5):624-8]. We deal specifically with study design and methodological issues for the assessment of pre-erythrocytic and blood-stage vaccines against P. vivax. The role of vaccines in blocking transmission of P. vivax is not considered as the methodological issues are similar to those for P. falciparum, though longer follow-up would be required because of the potential for relapse discussed below. In this paper we discuss the rationale and background to trials of P. vivax vaccines, requirements for Phase IIb and Phase III field trials, implementation of clinical trials, methods of measurement and analysis, and ethical aspects.