In Vivo Assessment of Drug Efficacy against Plasmodium falciparum Malaria: Duration of Follow-Up
Stepniewska K., Taylor WRJ., Mayxay M., Price R., Smithuis F., Guthmann J-P., Barnes K., Myint HY., Adjuik M., Olliaro P., Pukrittayakamee S., Looareesuwan S., Hien TT., Farrar J., Nosten F., Day NPJ., White NJ.
<jats:title>ABSTRACT</jats:title> <jats:p>To determine the optimum duration of follow-up for the assessment of drug efficacy against <jats:italic>Plasmodium falciparum</jats:italic> malaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (<jats:italic>r</jats:italic> <jats:sup>2</jats:sup> = 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.</jats:p>