Estimating intervention effectiveness in trials of malaria interventions with contamination
Open accessAbstract
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 buffer 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 effectiveness. Methods: A previously described analysis for CRTs is extended to SWCRTs and estimates of effectiveness 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 effect of adding pyriproxyfen to long-lasting insecticidal nets. Results: For the SolarMal trial, the contamination range was estimated to be 146 m ($$95\%$$ 95 % credible interval $$[0.052,\,0.923]$$ [ 0.052 , 0.923 ] km), together with a $$31.9\%$$ 31.9 % ($$95\%$$ 95 % credible interval $$[15.3,\,45.8]\%$$ [ 15.3 , 45.8 ] % ) reduction of Plasmodium infection, compared to the $$30.0\%$$ 30.0 % reduction estimated without accounting for contamination. The estimated effectiveness had an approximately linear relationship with coverage. For the AvecNet trial, estimated contamination effects were minimal, with insufficient data from the cluster boundary regions to estimate the effectiveness as a function of coverage. Conclusions: The contamination range in these trials of malaria interventions is much less than the distances Anopheles mosquitoes can fly. An appropriate analysis makes buffer zones unnecessary, enabling the design of more cost-efficient trials. Estimation of the contamination range requires information from the cluster boundary regions and trials should be designed to collect this.
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Multerer et al. 2021 incrementally replaced LLINs treated with permethrin and pyriproxyfen over two years in a SWCRT with 40 clusters.
“LLINs treated with permethrin and pyriproxyfen were incrementally replaced over two years in a SWCRT with 40 clusters”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [76]
The Methods section (“The AvecNet trial of long-lasting insecticidal nets”) confirms the two-year period, SWCRT design, and 40 clusters, but reverses the claimed direction of replacement: permethrin-only LLINs were replaced by LLINs treated with both permethrin and pyriproxyfen. (LLM, conf=0.92)
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- Authors
- Multerer, L., Vanobberghen, F., Glass, T. R., Hiscox, A., Lindsay, S. W., Takken, W., Tiono, A., & Smith, T.
- Affiliations
- Swiss Tropical and Public Health Institute (CH)
- London School of Hygiene & Tropical Medicine (GB)
- Durham University (GB)
- Wageningen University & Research (NL)
- Centre National de Recherche et de Formation sur le Paludisme (BF)
- Corresponding author
- Multerer, Lea
- ORCID
- Venue
- Malaria Journal
- Published
- 2021-10-20
- Volume
- 20
- Issue
- 1
- Pages
- 413-413
- ISSN
- 1475-2875 (ISSN-L)
- PMC
- PMC8527711
- OpenAlex
- W3205039344
- Cited by
- 9
- References
- 36
- Citations by year
- 2026: 4 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Malaria Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion, other-oa)
- Durham Research Online (Durham University) (acceptedVersion, other-oa)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- edoc (University of Basel)
- Funders
- Schweizerischer Nationalfonds zur F35örderung der Wissenschaftlichen Forschung (310030_162837)
- COmON Stichting
- Seventh Framework Programme (FP7/2007-2013)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Health Professions › General Health Professions › Health Policy Implementation Science
- Keywords
- malaria control interventions, contamination, stepped-wedge cluster randomized trial, mosquito movement, intervention coverage, buffer zones, pyriproxyfen, long-lasting insecticidal nets, malaria, trial design
- MeSH terms
- Mosquito Vectors, Family Characteristics, Humans, Insecticides, Malaria, Pyridines, Incidence, Cluster Analysis, Randomized Controlled Trials as Topic, Insecticide-Treated Bednets, Spatial Analysis
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