Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes – applications to influenza vaccine effectiveness

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http://hdl.handle.net/10138/325035

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Baum , U , Kulathinal , S & Auranen , K 2021 , ' Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes – applications to influenza vaccine effectiveness ' , Emerging Themes in Epidemiology , vol. 18 , no. 1 , 1 . https://doi.org/10.1186/s12982-020-00091-z

Title: Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes – applications to influenza vaccine effectiveness
Author: Baum, Ulrike; Kulathinal, Sangita; Auranen, Kari
Contributor: University of Helsinki, Department of Mathematics and Statistics
University of Helsinki, University of Turku
Date: 2021-01-14
Language: eng
Number of pages: 10
Belongs to series: Emerging Themes in Epidemiology
ISSN: 1742-7622
URI: http://hdl.handle.net/10138/325035
Abstract: Background: Non-sensitive and non-specific observation of outcomes in time-to-event data affects event counts as well as the risk sets, thus, biasing the estimation of hazard ratios. We investigate how imperfect observation of incident events affects the estimation of vaccine effectiveness based on hazard ratios. Methods: Imperfect time-to-event data contain two classes of events: a portion of the true events of interest; and false-positive events mistakenly recorded as events of interest. We develop an estimation method utilising a weighted partial likelihood and probabilistic deletion of false-positive events and assuming the sensitivity and the false-positive rate are known. The performance of the method is evaluated using simulated and Finnish register data. Results: The novel method enables unbiased semiparametric estimation of hazard ratios from imperfect time-to-event data. False-positive rates that are small can be approximated to be zero without inducing bias. The method is robust to misspecification of the sensitivity as long as the ratio of the sensitivity in the vaccinated and the unvaccinated is specified correctly and the cumulative risk of the true event is small. Conclusions: The weighted partial likelihood can be used to adjust for outcome measurement errors in the estimation of hazard ratios and effectiveness but requires specifying the sensitivity and the false-positive rate. In absence of exact information about these parameters, the method works as a tool for assessing the potential magnitude of bias given a range of likely parameter values.
Subject: 1181 Ecology, evolutionary biology
3111 Biomedicine
Influenza
Outcome measurement error
Proportional hazards model
Survival analysis
Vaccine effectiveness
Influenza
Outcome measurement error
Proportional hazards model
Survival analysis
Vaccine effectiveness
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