aa Colombo 2001

Methods	Randomised open trial to assess the efficacy of a trivalent subvirion vaccine
Participants	Healthy children from the area of Sassari (North Sardinia). All were aged 1 to 6 years and none had ever been immunised against influenza. Children with hypersensitivity reactions to eggs were excluded. Of the 398 meeting the inclusion criteria, 344 accepted to participate. 177 were randomly assigned to receive trivalent subvirion vaccine, 167 to the control group (no treatment)
Interventions	Trivalent subvirion influenza vaccine (Agrippal, Biocine S.p.A.) containing 15 microg of the high purified surface antigens from the following component strains : A/Johannesburg/33/94‐like, A/Singapore/6/86‐like, B/Beijing/184/93‐like. 2 doses 1 month apart were administered. Subjects immunisation took place between October 15 and November 15 , 1995 No treatment
Outcomes	Serological Paired sera for 17 participants, to test seroconversion and not diagnose influenza Effectiveness "Influenza‐like illness Follow‐up was carried out between December 1, 1995 and April 30, 1996. No participants were lost during this time. All children who developed influenza‐like symptoms were seen by the paediatrician. A clinical examination was conducted and repeated at the end of the illness with the aim to collect information regarding the duration of clinical symptoms and daycare absenteeism (also for the family members). Influenza‐like illness was defined as rectal temperature above 38.5°C and cough or sore throat lasting at least 72 hours" Safety "Systemic reactions (fever) Local reactions (erythema at the injection site) Parents were asked to contact the paediatrician in case of adverse event"
Funding Source	Government
Notes	The authors conclude that killed influenza vaccine is safe and effective in preschool children. Data about the rate of infection in parents were reported but it is not possible to state the number of parents involved. Only 85.5% of the children in the control group and 89.2% in the vaccinated group were in a daycare centre Quality of randomisation is suspect (different prevalence on passive smoking in the arms), lack of serological diagnosis despite 17 sera taken for seroconversion, no mention of circulating viruses in the season
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated list
Allocation concealment (selection bias)	High risk	No description
Blinding (performance bias and detection bias) All outcomes	High risk	No blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses
Summary assessments	High risk	Plausible bias that seriously weakens confidence in the results