| Methods |
Randomised, controlled, multicentre, observer‐blind trial assessing effectiveness, immunogenicity, and safety of both CCIV and TIV containing the strain recommended by WHO for the current season (2007 to 2008) |
| Participants |
Participants were recruited at 56 centres in the USA, Finland, and Poland.
Major exclusion criteria: health condition for which inactivated vaccine is recommended, employment prone to influenza transmission, influenza vaccination or laboratory‐confirmed influenza within 6 months of enrolment, history of Guillain‐Barré syndrome, a temperature of 37.8 °C and/or acute illness within 3 days of enrolment, and pregnancy or breastfeeding.
A total of 11,404 participants were randomised: 11,382 were vaccinated and 10,844 (95%) completed the study. |
| Interventions |
Individuals aged 18 to 49 years were randomised equally, with use of an interactive voice response system, to receive a single dose of CCIV, TIV, or placebo.
Both CCIV and TIV (Novartis Vaccines and Diagnostics) contained 15 µg of haemagglutinin per 0.5 mL dose of each of the following virus strains:
A/Solomon Islands/3/2006 (H1N1)–like
A/Wisconsin/67/2005 (H3N2)–like
B/Malaysia/2506/2004–like
Preparations were administered in the deltoid muscle of the non‐dominant arm. Only the vaccine administrator had access to the randomisation code. |
| Outcomes |
Safety
Study participants were monitored for 30 minutes after vaccination for immediate reactions. Participants recorded the occurrence, duration, and severity of local injection site and systemic reactions for 7 days after vaccination. Solicited reactions were graded as follows: mild, no limitation of normal daily activities; moderate, some limitation; or severe, unable to perform normal daily activities. Unsolicited reactions were recorded for 21 days after vaccination. Serious adverse events were monitored for the entire study (9 months).
Effectiveness
Influenza surveillance began 21 days after vaccination. Participants had to report to investigators the occurrence of influenza‐like illness symptoms (fever 37.8 °C plus sore throat or cough, as well as body aches, chills, headache, and runny or stuffy nose). An active survey was also performed by means of weekly phone calls.
Participants reporting influenza‐like illness symptoms underwent clinical evaluations; nasal and throat specimens were obtained for laboratory confirmation of influenza virus. Specimens were targeted for collection within 24 hours after symptom onset, with a window of 120 hours. Specimens were cultured on RhMK and tested by PCR.
Each study participant was observed during the 6‐month study surveillance period or for 6 months after vaccination, whichever was longer. Study duration was around 9 months.
Immunogenicity
It was assessed on the first 1045 participants enrolled at USA sites and randomised 8:25:2 to receive CCIV, TIV, or placebo. Serum samples were collected at baseline and 3 weeks after immunisation for seroprotection, seroconversion, and GMT determination. |
| Notes |
Financial support: "Novartis Vaccines was the funding source and was involved in all stages of the study conduct and analysis"
Potential conflicts of interest: "M.L., A.I., N.G., and S.H. are employees of Novartis Vaccines and Diagnostics. T.V. has received consultancy fees from MedImmune and speaker fees from MedImmune, Novartis, and Crucell in relation to meetings on influenza vaccination. S.F. and A.S.‐M.: no conflicts" |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
No description |
| Allocation concealment (selection bias) |
Low risk |
“Individuals ... were randomised equally, with use of an interactive voice response system, to receive a single dose of CCIV, TIV, or placebo.” |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
“This randomized, placebo‐controlled, observer‐blind trial evaluated ...”
“Only the vaccine administrator had access to the randomization code.”
No information about the appearance of the preparation is provided in the text. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Flow of participants during the study is reported and described. Loss to follow‐up amounts to about 5% at study end and is balanced through the 3 arms. |
| Summary assessment |
Unclear risk |
Unclear |
