A nested case-control study of influenza vaccination was a cost-effective alternative to a full cohort analysis

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.