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

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this

Anders, Katherine L. ; Cutcher, Zoe ; Kleinschmidt, Immo ; Donnelly, Christl A. ; Ferguson, Neil M. ; Indriani, Citra ; Ryan, Peter A. ; O'Neill, Scott L. ; Jewell, Nicholas P. ; Simmons, Cameron P. / Cluster-randomized test-negative design trials : A novel and efficient method to assess the efficacy of community-level dengue interventions. In: American Journal of Epidemiology. 2018 ; Vol. 187, No. 9. pp. 2021-2028.
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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.",
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Cluster-randomized test-negative design trials : A novel and efficient method to assess the efficacy of community-level dengue interventions. / Anders, Katherine L.; Cutcher, Zoe; Kleinschmidt, Immo; Donnelly, Christl A.; Ferguson, Neil M.; Indriani, Citra; Ryan, Peter A.; O'Neill, Scott L.; Jewell, Nicholas P.; Simmons, Cameron P.

In: American Journal of Epidemiology, Vol. 187, No. 9, 01.01.2018, p. 2021-2028.

Research output: Contribution to journalArticleResearchpeer-review

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