title: The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection.
abstract: Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals. We robustly account for important sources of variation between and within individuals using a Bayesian framework. Study power is most dependent on the number of individuals in each treatment arm; inter-individual variation in vaccine efficacy and the number of blood samples taken per day matter relatively little. Due to high inter-individual variation in the number of first-generation parasites, hepatic vaccine trials required significantly more study subjects than erythrocytic vaccine trials. We provide power calculations for hypothetical malaria vaccine trials of various designs and conclude that so far, power calculations have been overly optimistic. We further illustrate how upcoming techniques like needle-injected CHMI may reduce required sample sizes.
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Luc E
authors.identifier: 0000-0002-4425-2264
authors.initials: LE
authors.lastname: Coffeng
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Sake J
authors.initials: SJ
authors.lastname: de Vlas
mesh_terms: D001499:Bayes Theorem; D035843:Biomedical Research / Q000379:methods / Q000592:standards; D002986:Clinical Trials as Topic; D019295:Computational Biology; D003198:Computer Simulation; D064368:Healthy Volunteers; D006801:Humans; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000517:prevention & control*; D015233:Models, Statistical; D010963:Plasmodium falciparum / Q000472:pathogenicity*
chemical_list: D017780:Malaria Vaccines