A threshold analysis of the cost-effectiveness of artemisinin-based combination therapies in sub-Saharan Africa

Artemisinin-based combination therapies (ACTs) are generally regarded as vital in addressing the growing problem posed by the development of antimalarial resistance across sub-Saharan Africa. However, the costs of the new ACTs are likely to be significantly higher than current therapies. Therefore, it is important to examine formally the cost-effectiveness of the more effective yet more expensive ACTs before advocating a switch in policy. Importantly, any such economic evaluation must consider the temporal dynamics of drug resistance, and not just focus on the static question of whether switching today would be cost-effective at current levels of resistance, particularly since the development of new antimalarials in the future is so uncertain. However, predicting the future changes in drug resistance is a major difficulty in accurately quantifying the relative costs and health outcomes associated with different drug therapies over time. Here, we use a simple decision tree model to estimate the incremental cost-effectiveness of using ACTs, compared with persisting with current therapies, over 5-, 10-, and 15-year periods. We describe the dynamics of drug resistance using a general logistic growth function, in which the starting frequency of resistance and maximum growth may be altered. However, rather than make assumptions about the absolute rate at which resistance to ACTs will progress, we allow the ratio of the growth rate of resistance to ACTs relative to that of current therapies to vary. Defining the growth rate of ACT resistance in this manner allows us to calculate the threshold ratio at which ACTs would no longer appear cost-effective, for any starting conditions of resistance to current therapies and ACTs, and over any time period. The influence of uncertainty in other decision tree parameters on the threshold ratio values is also quantified, using Monte Carlo simulation techniques. This analysis shows that ACTs are more than 95% likely to be cost-effective under most conditions, other than very low levels of initial resistance to sulfadoxine/pyrimethamine and a five-year time frame. These predictions are conservative in that 95% certainty is a stringent decision rule favoring the rejection of new policies. The importance of other variables not included in the analysis for the robustness of the findings are discussed (e.g., consideration of the entire population at risk for malaria, the affordability of ACTs in specific settings, and the growth of resistance modeled according to population genetic parameters).