Ratjen 2010.

Methods	RCT. Parallel design. Duration: 27 months. Multicentre (21 centres) based in Europe (Germany, France, Spain, Austria, UK, Netherlands).
Participants	123 participants with CF free of P aeruginosa (88 randomised ‐ 31 participants not randomised because of high P aeruginosa antibody titres and 4 for other reasons). Age (mean (SD)): 28‐day TIS 8.7 (7.2) years, 56‐day TIS 8.7 (10.5) years. Gender: 28‐day TIS 26 (58%) males, 19 (42%) females; 56‐day TIS 22 (51%) males, 21 (49%) females. Lung function (mean (SD) FEV1 % predicted): 28‐day TIS 80.2 (18.9), 56‐day TIS 87.0 (19.2).
Interventions	Group 1 (n = 45): 28 days of tobramycin solution for inhalation (TSI) (300 mg 2x daily), then stopped treatment. Group 2 (n = 43): 28 days of tobramycin solution for inhalation (TSI) (300 mg 2x daily), then randomised to a further 28 days (56 days in total).
Outcomes	Primary outcome Median time to recurrence of any strain of P aeruginosa. Secondary outcomes Proportion of patients free of P aeruginosa 1 month after the end of treatment Number and length of hospital admissions for respiratory indications Occurrence of other pathogens Changes in FEV₁, FVC & FEF25‐75 Weight, height and BMI.
Notes	Also known as ELITE trial.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised, but no description of randomisation techniques given.
Allocation concealment (selection bias)	Unclear risk	Did not report how allocation was concealed.
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label study, no attempt at blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	65 participants from 88 randomised achieved primary outcome. A total of 52 participants prematurely withdrawn from trial. 27 participants withdrew from the 28‐day treatment group with the following reasons: loss to follow up (n = 1); protocol deviation (n = 4); recurrence/non‐eradication (n = 21); other (n = 1). 25 participants withdrew from the 56‐day treatment group for the following reasons: withdrawn consent (n = 1); loss to follow up (n = 2); protocol deviation (n = 2); recurrence/no eradication (n = 19); abnormal audiology test (n = 1).
Selective reporting (reporting bias)	High risk	Study reports there were no major short‐ or long‐term (3 and 27 months) changes in spirometry, but does not record the figures for either of the 2 groups. Also, only summary statements and no numerical data are provided for weight, height or BMI.
Other bias	Unclear risk	Recruited fewer participants than planned; actually randomised 88 participants (primary outcome evaluable in 65) ‐ planned randomisation of 100 participants. Did not randomise 35 participants from the recruited cohort of 123 participants: 31 because of high P aeruginosa antibody levels, one for an adverse event, one where consent was withdrawn, one for a protocol deviation and one 'other' (unspecified) reason. Participants with raised antibody levels were not included because the investigators believed that they were chronically infected with P aeruginosa based on their antibody results. This trial was initially supported by Chiron and later Novartis Pharma, the manufacturer of TSI.