Towards optimal design of anti-malarial pharmacokinetic studies

Optimal design methods incorporate prior knowledge of the pharmacokinetic profile of the drug, the statistical methods used to analyse data from population pharmacokinetic studies, and also the practical constraints of sampling the patient population. The methods determine the statistical efficiency of the design by evaluating the information of the candidate study design prior to the pharmacokinetic study being conducted.In a hypothetical population pharmacokinetic study of intravenous artesunate, where the number of patients and blood samples to be assayed was constrained to be 50 and 200 respectively, an evaluation of varying elementary designs using optimal design methods found that the designs with more patients and less samples per patient improved the precision of the pharmacokinetic parameters and inter-patient variability, and the overall statistical efficiency by at least 50%.Optimal design methods ensure that the proposed study designs for population pharmacokinetic studies are robust and efficient. It is unethical to continue conducting population pharmacokinetic studies when the sampling schedule may be insufficient to estimate precisely the pharmacokinetic profile.Despite significant progress in malaria control over the last few years, malaria-related morbidity and mortality are still considerable[1]. The contribution of inadequate dosage regimens (dose and frequency of administration) to anti-malarial treatment failure and the emergence of resistance has been underappreciated[2]. Most recommended dosage regimens are based on studies in non-pregnant adult patients, yet young children and pregnant women are at the greatest risk of treatment failure and often bear the brunt of the malaria burden[2]. Optimizing current treatment regimens could provide major health benefits and is a necessary prerequisite for malaria elimination. Effective treatment of malaria requires that the dose and frequency of administration of the anti-malarial drug provide drug con