Abstract
A recent discussion meeting convened by the Medicines for Malaria Venture examined how best to manage the discovery and preclinical pipeline to achieve novel combination therapies which would address the key clinical needs in malaria. It became clear that dose optimisation of components within combination therapy was a key issue in achieving antimalarial efficacy and for preserving that efficacy against parasite resistance emergence. This paper outlines some of the specific issues in malaria that cause dose-ranging and dose-optimisation studies to be particularly challenging and discusses the potential of factorial study design to address such challenges.
Highlights
IntroductionBy 2001, Plasmodium falciparum resistance to conventional antimalarials had left many countries with no effective, affordable treatment (Roll Back Malaria 2001; World Health Organization 2010)
Artemisinin revolutionised antimalarial therapy and forestalled a catastrophe
Box 1 Challenges for novel antimalarial combination therapy drug development compared with the development of artemisinin-based combination therapy (ACT)
Summary
By 2001, Plasmodium falciparum resistance to conventional antimalarials had left many countries with no effective, affordable treatment (Roll Back Malaria 2001; World Health Organization 2010). Attendant to this was an increase in mortality, morbidity, and the frequency and severity of malaria epidemics (Roll Back Malaria 2001). Today, artemisininbased combination therapy (ACT) is highly efficacious with day-28 cure rates generally exceeding 95% (adjusted for reinfection with polymerase chain reaction genotyping), and costs less than $1 per adult treatment (World Health Organization 2010). Drugs that interrupt malaria transmission: a key component of malaria elimination efforts (The malERA Consultative Group on Drugs 2011) In this revival of antimalarial drug development, safety and efficacy remain the dominant objectives. Box 1 Challenges for novel antimalarial combination therapy drug development compared with the development of artemisinin-based combination therapy (ACT)
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