Temporal Confounding in the Test-Negative Design
Open Access
- 16 May 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in American Journal of Epidemiology
- Vol. 189 (11), 1402-1407
- https://doi.org/10.1093/aje/kwaa084
Abstract
In the test-negative design, routine testing at health-care facilities is leveraged to estimate the effectiveness of an intervention such as a vaccine. The odds of vaccination for individuals who test positive for a target pathogen is compared with the odds of vaccination for individuals who test negative for that pathogen, adjusting for key confounders. The design is rapidly growing in popularity, but many open questions remain about its properties. In this paper, we examine temporal confounding by generalizing derivations to allow for time-varying vaccine status, including out-of-season controls, and open populations. We confirm that calendar time is an important confounder when vaccine status varies during the study. We demonstrate that, where time is not a confounder, including out-of-season controls can improve precision. We generalize these results to open populations. We use our theoretical findings to interpret 3 recent papers utilizing the test-negative design. Through careful examination of the theoretical properties of this study design, we provide key insights that can directly inform the implementation and analysis of future test-negative studies.Funding Information
- National Institute of Allergy and Infectious Diseases (R01 AI139761)
This publication has 25 references indexed in Scilit:
- Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic reviewExpert Review of Vaccines, 2014
- Is it necessary to adjust for calendar time in a test negative design?Vaccine, 2014
- Variable definitions of the influenza season and their impact on vaccine effectiveness estimatesVaccine, 2013
- The case test-negative design for studies of the effectiveness of influenza vaccineVaccine, 2013
- The test-negative design for estimating influenza vaccine effectivenessVaccine, 2013
- Effectiveness of Non-Adjuvanted Pandemic Influenza A Vaccines for Preventing Pandemic Influenza Acute Respiratory Illness Visits in 4 U.S. CommunitiesPLOS ONE, 2011
- Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trialThe Lancet, 2009
- Estimation of risk ratios in case‐base studies with competing risksStatistics in Medicine, 1990
- Assessment of the Protective Efficacy of Vaccines against Common Diseases Using Case-Control and Cohort StudiesInternational Journal of Epidemiology, 1984
- Pneumococcal Disease after Pneumococcal VaccinationThe New England Journal of Medicine, 1980