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Updated: Jul 28, 2026

A Luciferase-fluorescent Reporter Influenza Virus for Live Imaging and Quantification of Viral Infection
Published on: August 14, 2019
A nested case-control study of influenza vaccination was a cost-effective alternative to a full cohort analysis
1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, The Netherlands. e.hak@med.uu.nl
Objective:
In the absence of trial results that are applicable to the target population, nested case-control studies might be an alternative to full-cohort analysis. We compared relative and absolute estimates of associations in an influenza vaccine study using both designs.
Study Design And Setting:
Data from elderly persons enrolled during six consecutive influenza seasons were used (147,551 person-periods). The endpoints "hospitalization for pneumonia or influenza" (P&I) or "death" were used combined and separately to define three types of cases. Controls for the case-control samples were randomly selected from the remainder of the total cohort at different ratios (1:1 to 1:4). Logistic regression analysis was used to assess adjusted vaccine effectiveness (VE). Sampling fractions were used to determine the number needed to treat to prevent one outcome. Receiver-operator-curve analysis was conducted to estimate the area under the curve (AUC) as a measure of discriminative capacity of the prognostic model.
Results:
In all, 978 P and I hospitalizations and 1,339 deaths were observed. The adjusted estimates of relative estimates (VE, AUC) and their corresponding 95% confidence intervals were virtually the same using both study designs, notably when the case-control ratio was high (1:4).
Conclusion:
A nested case-control design can provide valid and precise estimates of associations and is a cost-effective alternative for full-cohort analysis.

