WHO antimalarial trial guidelines: good science, bad news?

Estimating antimalarial drug efficacy requires differentiating treatment failures from new infections arising during the several-week follow-up period in drug trials. Genetic profiling of malaria infections can guide this decision but is notoriously difficult in practice. Previous World Health Organisation (WHO) guidelines were based on assumptions with an inherently high risk of underestimating failure rates. A recent update to WHO guidelines recognises a wider range of analyses to overcome these limitations. We discuss these new analyses and their underlying logic. Drug failure rate estimates in moderate to high transmissions areas will become more accurate but will likely rise twofold due to better detection of treatment failures, and the malaria community needs to anticipate and prepare for potentially large increases in estimated failure rates.