A1 Refereed original research article in a scientific journal

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




AuthorsBaum Ulrike, Kulathinal Sangita, Auranen Kari

PublisherBMC

Publication year2021

JournalEmerging Themes in Epidemiology

Journal name in sourceEMERGING THEMES IN EPIDEMIOLOGY

Journal acronymEMERG THEMES EPIDEMI

Article numberARTN 1

Volume18

Issue1

Number of pages10

eISSN1742-7622

DOIhttps://doi.org/10.1186/s12982-020-00091-z

Web address https://ete-online.biomedcentral.com/articles/10.1186/s12982-020-00091-z

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/53622376


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.

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