ba Kissling 2011

Methods	Third season of I‐MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), multicentre, case‐control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically‐attended ILI laboratory‐confirmed as influenza The 8 study sites included in the multicentre, case‐control study were settings in France, Hungary, Ireland, Italy, Poland, Portugal, Romania and Spain. In six study sites, primary care practitioners belonging to the national influenza sentinel networks were invited to participate in the study. In Portugal and Italy, practitioners other than those participating in the national influenza sentinel networks were also invited to participate   The study population consisted of non‐institutionalised patients consulting a participating practitioner for ILI or ARI (France only) who had a nasal or throat swab taken less than eight days after symptom onset and with no contraindication for influenza vaccination. In Hungary the study population was restricted to those 18 years or older. We defined the start of the study period in each of the study sites as more than 14 days after the start of the 2010 to 11 influenza vaccination campaign   Practitioners in Ireland, Poland Portugal, Spain and France swabbed all ILI/ARI patients aged 65 and over, in Hungary they swabbed all ILI patients 60 and over and in Italy they systematically swabbed 1 ILI/ARI patient aged 65 and over per week. In all study sites practitioners systematically sampled ILI/ARI patients to swab among the other age groups, apart from Romania where practitioners swabbed all ILI patients in all age groups   In all study sites, practitioners interviewed the ILI patients using country‐specific questionnaires. The common variables collected in the eight study sites included ILI signs and symptoms, age, sex, pregnancy, presence of chronic conditions, severity of the chronic disease measured as the number of hospitalisations for the chronic disease in the previous 12 months, smoking history (none, past, current smoker), number of practitioner visits in the previous 12 months, 2009 to 10 pandemic vaccination status, seasonal influenza vaccination in the 2009 to 10 and in the 2010 to 11 season ILI patient were excluded if they presented ILI symptoms before the week of onset of the first recruited influenza case. For each study site, ILI patients were excluded if presenting either after the onset week of the last recruited influenza case or after the onset week of the case prior to 2 consecutive weeks of no positive case recruited   To estimate VE against A(H1N1)2009 and against influenza B virus, we based the exclusion criteria on the week of onset of the first and last A(H1N1)2009 and influenza B case respectively
Participants	Description of cases A case was defined as a patient with signs and symptoms adhering to the EU ILI case definition (sudden onset of symptoms and at least 1 of the following four systemic symptoms: fever or feverishness, malaise, headache, myalgia and at least 1 of the following three respiratory symptoms: cough, sore throat, shortness of breath), who was swabbed and tested positive for influenza using real‐time polymerase chain reaction (qRT‐PCR) or culture   Description of controls Controls were EU ILI patients who were swabbed and tested negative for influenza
Interventions	An individual was considered vaccinated if he/she received at least 1 dose of the 2010 to 11 seasonal vaccine more than 14 days before the date of onset of ILI symptoms
Outcomes	Laboratory Those who were swabbed and tested positive for influenza using qRT‐PCR or culture. Swabs were tested for influenza at the respective countries’ National Influenza Reference Laboratory (in Spain, the laboratories of the regional sentinel networks integrated in the Spanish Influenza Sentinel Surveillance System). In each country, all or a subset of influenza isolates were antigenically characterised. Laboratory viral detection, typing, subtyping and variant analysis performed in each of the National Reference Laboratories are described elsewhere (European Centre for Disease Prevention and Control (ECDC) (2010) European Influenza Surveillance Network (EISN). Table 2: Characteristics of the virological surveillance systems participating in EISN, Available from: http:// www.ecdc.europa.eu/en/activities/surveillance/EISN/laboratory_network/ ages/laboratory_network.aspx. Accessed October 2011)
Funding Source	Government
Notes	In conclusion, the I‐MOVE multicentre case‐control study provided summary influenza VE estimates across Europe and showed a moderate VE against medically attended ILI laboratory‐confirmed influenza in a season of good match between the circulating influenza strains and the strains included in the 2010 to 11 trivalent vaccine. Next season further study sites may be included in the pooled analysis and current study sites will focus on increasing sample size through recruitment of more GPs in order to obtain more precise estimates, to carry out an adjusted 2‐stage pooled analysis and to obtain age‐specific estimates by influenza type among the target group for vaccination. Even if the trivalent inactivated influenza vaccines may only provide a moderate protection against medically‐attended ILI laboratory‐confirmed as influenza, they remain, until more efficient vaccines are available, the most effective measure to prevent influenza infection and its consequences Well conducted and reported case‐control study
Risk of bias
Bias	Authors' judgement	Support for judgement
CC‐Case Selection	Low risk	Independent validation
CC‐Control Selection	Low risk	Drawn from the same population
CC‐Comparability	Low risk	Study controls for age group, sex, presence of chronic conditions, at least 1 hospitalisation in the previous 12 months for chronic disease, smoking history, number of practitioner visits in the previous 12 months
CC‐Exposure	Low risk	Secure record
Summary assessments	Low risk	Possible under‐estimation