Consensus on methods to assess exposure to antimalarial drugs

Effective malaria treatment requires that patients achieve sufficient drug levels in their blood to remove parasites in a timely way without experiencing unwanted side effects. Before approving a drug for use, regulatory authorities ask that pharmaceutical companies define these levels in controlled clinical trials. Such studies usually involve non-pregnant adults and older children with acute, uncomplicated malaria, whereas the reality in the field is that many patients with malaria are infants, pregnant women or have other diseases such as HIV/AIDS, tuberculosis or suffer malnutrition, which may affect their ability to absorb the drug. Therefore it is important to know that patients in these special risk groups also receiving optimal dosages. Pooling studies increases sample sizes, so that sub-population effects can be identified with higher statistical certainty. Agreed methodology overcomes inter-study assay and analysis variations - the main constraint on data pooling. 

Prof Niklas Lindegardh (1), Director of the WWARN Pharmacology QA/QC Programme and Chairman of the Consensus Meeting, commented: “We hope that the report will be a reference document for investigators conducting clinical trials, for laboratories performing antimalarial drug assays, and for national malaria control programmes, study sponsors and regulatory authorities responsible for evaluating antimalarial drugs.” Contents cover bioanalytical methodology, sample collection and storage, core protocols for studies of pharmacokinetics and pharmacodynamics, and acceptance and evaluation criteria for each bioanalytical assay.

Following the development of the consensus methodology, the WWARN Pharmacology Module brought together 32 scientists actively involved in performing antimalarial pharmacokinetic assays and data analysis. The group met back in October 2011in South Africa to consider how the quality assayed data, generated by following the newly-published consensus methodology, might be analysed to answer outstanding questions on the relationship between patient populations, dosing, drug exposure and treatment response. Following this consensus meeting, a hands-on workshop involving emerging scientists used the agreed classical PK-PD analysis and population modelling approaches to analyse their own data set. Slide presentations from this workshop are available.

Enthusiastic about the outcome, Dr George O Adjei of the Center for Tropical Clinical Pharmacology and Therapeutics at the University of Ghana Medical School reflected, “The meeting provided an excellent opportunity to discuss some of the challenges in current malaria treatment with experienced investigators and practitioners in this field. The opportunity to learn from, and participate in, first-hand discussions on topics in the WHO/WWARN guidance document on Methods and techniques for assessing exposure to antimalarial drugs in clinical field studies was insightful and helpful. It was also refreshing that the organizers actively reached out to individuals from malaria endemic countries, like myself. The meeting was one of my best experiences so far.”

(1) Professor Niklas Lindegardh died suddenly on January 18, 2012 after this article was written. He is remembered in a special condolence message.