Cluster-randomized test-negative design trials: A novel and efficient method to assess the efficacy of community-level dengue interventions

Katherine L. Anders, Zoe Cutcher, Immo Kleinschmidt, Christl A. Donnelly, Neil M. Ferguson, Citra Indriani, Peter A. Ryan, Scott L. O'Neill, Nicholas P. Jewell, Cameron P. Simmons

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    Abstract

    Cluster-randomized controlled trials are the gold standard for assessing efficacy of community-level interventions, such as vector-control strategies against dengue. We describe a novel cluster-randomized trial methodology with a test-negative design (CR-TND), which offers advantages over traditional approaches. This method uses outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest,who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing.We used simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. We demonstrated that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. Analytical considerations for an odds ratio-based effect estimate arising from clustered data and potential approaches to analysis are also discussed briefly. We concluded that application of the test-negative design to certain clusterrandomized trials could increase their efficiency and ease of implementation.

    Original languageEnglish
    Pages (from-to)2021-2028
    Number of pages8
    JournalAmerican Journal of Epidemiology
    Volume187
    Issue number9
    DOIs
    Publication statusPublished - 1 Jan 2018

    Keywords

    • Case-control
    • Cluster-randomized trial
    • Dengue
    • Efficacy
    • Odds ratio
    • Study design
    • Test-negative design
    • Wolbachia

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