Right sizing for vaccine effectiveness studies: how many is enough for reliable estimation?

Abstract

Background The precision of vaccine effectiveness (VE) estimates is dependent on sample size and sampling methods. In Victoria, participating general practitioners (GPs) are not limited by the number of influenza-like illness (ILI) patients they collect respiratory samples (swabs) from in sentinel surveillance. However, in the context of scarce resources it is of interest to determine the minimum sample size needed for reliable estimates. Methods Following the test-negative design, patients with ILI were recruited by GPs and tested for influenza. Descriptive analyses were conducted to assess possible selection bias introduced by GPs. VE was calculated by logistic regression as [1 – odds ratio] x 100% and adjusted for week of presentation and age. Random 20% and 50% samples were selected without replacement to estimate the effect of swab rates on VE estimates. Results GPs swabbed a smaller proportion of patients aged ≥65 years (45.9%, n=238) than those <5 (75.6%, n=288), 5–17 (67.9%, n=547) and 18–64 (75.6%, n=2662) years. Decreasing the swab rate did not alter VE point estimates significantly. However, it reduced the precision of estimates and in some instances resulted in too small a sample size to estimate VE. Conclusion Imposing a 20% or 50% swabbing rate produces less robust VE estimates. The number of swabs required per year to produce precise estimates should be dictated by seasonal severity, rather than an arbitrary rate. It would be beneficial for GPs to swab patients systematically by age group to ensure there are sufficient data to investigate VE against a particular subtype in a given age group.