The article The test-negative design for estimating influenza vaccine effectiveness (Vaccine 2013;31(17):2165-8) explains the rationale, assumptions and analysis of the test-negative study as applied to influenza VE. Study subjects are all persons who seek care for an acute respiratory illness and influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subject testing negative. This design is less susceptible to bias due to misclassification of infection and the confounding by health care-seeking behaviour, at the cost of difficult-to-test assumptions.
Effectiveness of rotavirus vaccines in preventing cases and hospitalizations due to rotavirus gastroenteritis in Navarre, Spain (Vaccine 2012;30(3):539-43) evaluates effectiveness using a test negative case-control design based on electronic clinical reports. Cases were children with confirmed rotavirus and controls were those who tested negative for rotavirus in all samples. The test-negative design was based on an assumption that the rate of gastroenteritis caused by pathogens other than rotavirus is the same in both vaccinated and unvaccinated persons. This approach may rule out differences in parental attitude when seeking medical care and of physician differences in making decisions about stool sampling or hospitalisation. A limitation is sensitivity of antigen detection which may underestimate vaccine effectiveness. In addition, if virus serotype is not available, it is not possible to study the association between vaccine failure and a possible mismatch of vaccine strains and circulating strains of virus.
The article 2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals (EuroSurveill 2015;20(2):pii=21011) illustrates a multicentre test-negative case-control study to estimate influenza VE in 18 hospitals. It is believed that confounding due to health-seeking behaviour is minimised since, in the study sites, all people needing hospitalisation are likely to be hospitalised. The study Trivalent inactivated seasonal influenza vaccine effectiveness for the prevention of laboratory-confirmed influenza in a Scottish population 2000 to 2009 (EuroSurveill 2015;20(8):pii=21043) applied this method using a Scotland-wide linkage of patient-level primary care, hospital and virological swab data over nine influenza seasons and discusses strengths and weaknesses of the design in this context.
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|