The ongoing development of new antimalarial drugs, and the increasing use of controlled human malaria infection (CHMI) studies to investigate their activity in early stage clinical trials require the development of methods to analyse their pharmacodynamic effect. This is especially so for studies where quantitative PCR (qPCR) is becoming the preferred method for assessing parasite clearance as the study endpoint. We report the development and validation of an analytic approach for qPCR-determined parasite clearance data. First, in a clinical trial with the licensed antimalarial combination sulfadoxine-pyrimethamine (S/P), qPCR data were collected from 12 subjects and used to determine qPCR replicate variability and to identify outliers. Then, an iterative analytic approach based on modelling the log-linear decay of parasitemia following drug treatment was developed to determine the Parasite Reduction Rate (PRR) and parasite-clearance half life, both measures of parasite clearance. This analytic approach was then validated with data from 8 subjects enrolled in a second study with the licensed antimalarial drug mefloquine. Using this method the PRR and parasite clearance half lives for S/P and Mefloquine were determined to be 38,878 (95%CI: 17,396-86,889), 3.15 (95% CI: 2.93-3.41) days, and 157 (95%CI: 130-189), 6.58 (95% CI: 6.35-6.83) days, for the respective studies. No serious adverse events occurred in the two trials, and pharmacokinetic values were within expected ranges for sulfadoxine and pyrimethamine. The robust statistical method we have developed to analyse qPCR-derived pharmacodynamic data from CHMI studies will facilitate the assessment of the activity of a range of experimental antimalarial drugs now entering clinical trials.