According to a commentary, the case test-negative study (or test-negative design) has emerged as the preferred observational study design from which to calculate influenza vaccine effectiveness (VE) over the last 10 years. It is a prospective variant of the traditional case-control study design, in which the case (test positive) or control (test negative) status of the study participants is not known at the time of their recruitment into the study: patients presenting with a defined acute respiratory illness are tested for influenza and those who test positive become cases and those who test negative become controls. The commentator notes that this design is now established as a reliable and more practical means of measurement of VE in the field than are more expensive and time-consuming clinical trials, but despite the rapid evolution of the case test-negative study design, the effects of various important aspects remain to be further developed and explored.