Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta analysis

by WorldWide Antimalarial Resistance Network (WWARN) Methodology Study Group – including Kiechel JR. Malaria Journal, 2019, doi:10.1186/s12936-019-2837-4

Summary: The primary endpoint for therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria is recrudescence of the original infection. In the case of new infections where the parasite load outnumbers existing low levels of parasitaemia, recrudescence may not be detected, thus new infections constitute a ‘competing risk event’. Two methods– 1 minus Kaplan-Meier (K-M), which considers new infections acquired during the follow-up period as censored and the Cumulative Incidence Function (CIF), which accounts for them as a competing risk event – were used to determine the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository in 31,379 patients. The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infections was high. The CIF approach provides an alternative way of deriving failure estimates in antimalarial trials, particularly in high transmission settings.

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