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

Journal article

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 cluster-randomized trials could increase their efficiency and ease of implementation.

Authors: Anders, K; Cutcher, Z; Kleinschmidt, I; Donnelly, C; Ferguson, N

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: American Journal of Epidemiology
• Volume: 187
• Issue: 9
• Pages: 2021-2028
• Publication date: 2018-05-07
• Acceptance date: 2018-04-27
• DOI: 10.1093/aje/kwy099
• EISSN: 1476-6256
• ISSN: 0002-9262
• Pmid: 29741576
• Language: English
• Keywords: study design; odds ratio; case-control; efficacy; cluster-randomized trial; dengue; Wolbachia; test-negative design