Hypothesis testing and sample size considerations for the test-negative design.


Journal

BMC medical research methodology
ISSN: 1471-2288
Titre abrégé: BMC Med Res Methodol
Pays: England
ID NLM: 100968545

Informations de publication

Date de publication:
16 Jul 2024
Historique:
received: 20 12 2023
accepted: 05 07 2024
medline: 17 7 2024
pubmed: 17 7 2024
entrez: 16 7 2024
Statut: epublish

Résumé

The test-negative design (TND) is an observational study design to evaluate vaccine effectiveness (VE) that enrolls individuals receiving diagnostic testing for a target disease as part of routine care. VE is estimated as one minus the adjusted odds ratio of testing positive versus negative comparing vaccinated and unvaccinated patients. Although the TND is related to case-control studies, it is distinct in that the ratio of test-positive cases to test-negative controls is not typically pre-specified. For both types of studies, sparse cells are common when vaccines are highly effective. We consider the implications of these features on power for the TND. We use simulation studies to explore three hypothesis-testing procedures and associated sample size calculations for case-control and TND studies. These tests, all based on a simple logistic regression model, are a standard Wald test, a continuity-corrected Wald test, and a score test. The Wald test performs poorly in both case-control and TND when VE is high because the number of vaccinated test-positive cases can be low or zero. Continuity corrections help to stabilize the variance but induce bias. We observe superior performance with the score test as the variance is pooled under the null hypothesis of no group differences. We recommend using a score-based approach to design and analyze both case-control and TND. We propose a modification to the TND score sample size to account for additional variability in the ratio of controls over cases. This work enhances our understanding of the data generating mechanism in a test-negative design (TND) and how it is distinct from that of a case-control study due to its passive recruitment of controls.

Identifiants

pubmed: 39014324
doi: 10.1186/s12874-024-02277-4
pii: 10.1186/s12874-024-02277-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

151

Informations de copyright

© 2024. The Author(s).

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Auteurs

Yanan Huo (Y)

Gilead Sciences, Inc, Foster City, CA, USA.

Yang Yang (Y)

Department of Statistics, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, USA.

M Elizabeth Halloran (ME)

Department of Biostatistics, University of Washington, Seattle, WA, USA.
Fred Hutchinson Cancer Center, Seattle, WA, USA.

Ira M Longini (IM)

Department of Biostatistics, University of Florida, Gainesville, FL, USA.

Natalie E Dean (NE)

Department of Biostatistics & Bioinformatics, Emory University, Atlanta, GA, USA. nataliedean@emory.edu.

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