| Study characteristics |
| Methods |
Randomised 1:1 in blocks of 12 stratified by centre. Double‐blinding. Public funding. |
| Participants |
483 randomised, all in intention‐to‐treat analyses, and 381 in per protocol analyses. Method of diagnosis of cystic fibrosis not stated ("conventional criteria"). Age: 1 or 2 years (both limits stated) to 18 years, free of P. aeruginosa. 239 children received vaccine and 244 placebo. |
| Interventions |
4 doses of vaccine consisting of pseudomonas flagella proteins of subtypes a0a1a2 and b from strains 1210 and 5142, respectively, every 4 weeks (first 3 doses) and last dose after 1 year, or placebo. |
| Outcomes |
Primary: infection with P. aeruginosa, diagnosed by a positive throat swab or positive antibody titre towards other antigens (exotoxin A, alkaline protease, or elastase) than the flagella proteins in the vaccine.
Another outcome was added during the trial: chronic infection, diagnosed by 3 positive swabs or titres during 1 year.
Other outcomes were: specific antibodies against vaccine components and flagella subtypes; adverse events. FEV1 was measured but no data were provided. |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
"Random numbers algorithm of Wichmann and Hill". |
| Allocation concealment (selection bias) |
Unclear risk |
"Syringes numbered with the randomisation code". "Patients...assigned...in ascending numerical order as they were enrolled consecutively". |
| Blinding (performance bias and detection bias)
All outcomes |
Low risk |
Placebo contained same ingredients, apart from vaccine; no information about appearance. Statistical analysis plan finalised before unblinding, and allocation list not provided to statistician until closure of data entry. Statistician independent of company that provided drugs. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Intention‐to‐treat analyses. |
| Selective reporting (reporting bias) |
High risk |
FEV1 was measured but no data were provided. There was a Supervisory Board, but no rules are described for interim analyses or for stopping the trial. Author informed us that the role of the board was to monitor systematic reactions to the vaccine after 48 patients had been treated. |
| Other bias |
High risk |
Significant differences at baseline despite contrasting information in the trial report. One‐sided significance level used in power calculation, although it is known that antibodies may be harmful. |
