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.
Highlights
In 2015, malaria caused an estimated 438,000 deaths (236,000–635,000) [1], most of which were associated with Plasmodium falciparum (Pf) infections
To optimize power calculations for malaria vaccine trials, we developed a non-linear, Bayesian statistical model for parasite kinetics as measured by quantitative real-time polymerase chain reaction, using existing data from mosquito-based controlled human malaria infection (CHMI) experiments
We provide improved, robust power calculations for various hypothetical malaria vaccine trials, taking account of important sources of variation between and within individuals
Summary
In 2015, malaria caused an estimated 438,000 deaths (236,000–635,000) [1], most of which were associated with Plasmodium falciparum (Pf) infections. Only the RTS,S vaccine has shown promising results (30%–65% protection against clinical malaria) [2,3,4,5,6], with a recent large, multi-center phase three trial showing 45.7% protection against clinical malaria in infants and children aged 5–17 months over a period of 18 months after three vaccine doses [7]. Before any malaria vaccine can be tested in the field, its efficacy and safety need to be evaluated in controlled settings, which is most often done by means of controlled human malaria infection (CHMI) [9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
