Estimating intervention effectiveness in trials of malaria interventions with contamination

Abstract

Background: In cluster randomized trials (CRTs) or stepped wedge cluster randomized trials (SWCRTs) of malaria interventions, mosquito movement leads to contamination between trial arms unless bufer zones separate the clusters. Contamination can be accounted for in the analysis, yielding an estimate of the contamination range, the distance over which contamination measurably biases the efectiveness. Methods: A previously described analysis for CRTs is extended to SWCRTs and estimates of efectiveness are provided as a function of intervention coverage. The methods are applied to two SWCRTs of malaria interventions, the SolarMal trial on the impact of mass trapping of mosquitoes with odor-baited traps and the AvecNet trial on the efect of adding pyriproxyfen to long-lasting insecticidal nets. Results: For the SolarMal trial, the contamination range was estimated to be 146 m (95% credible interval [0.052, 0.923] km), together with a 31.9% (95% credible interval [15.3, 45.8]%) reduction of Plasmodium infection, compared to the 30.0% reduction estimated without accounting for contamination. The estimated efectiveness had an approximately linear relationship with coverage. For the AvecNet trial, estimated contamination efects were minimal, with insufcient data from the cluster boundary regions to estimate the efectiveness as a function of coverage. Conclusions: The contamination range in these trials of malaria interventions is much less than the distances Anopheles mosquitoes can fy. An appropriate analysis makes bufer zones unnecessary, enabling the design of more cost-efcient trials. Estimation of the contamination range requires information from the cluster boundary regions and trials should be designed to collect this.