Cluster-Randomized Test-Negative Design Trials: A Novel and Efficient Method to Assess the Efficacy of Community-Level Dengue Interventions

Am J Epidemiol. 2018 Sep 1;187(9):2021-2028. doi: 10.1093/aje/kwy099.

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

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dengue / prevention & control*
  • Humans
  • Research Design*