Jaques 2008.

Study characteristics
Methods	Double‐blind, randomised, cross‐over study. Duration (total): 6 weeks; each arm of cross‐over study lasted 2 weeks with 2 week wash‐out period in between. Location: Australia, New Zealand. (Multicentre)
Participants	49 participants with CF, 39 randomised. Mean age: 19.1 years, range 8 ‐ 48 years. Gender split: 41% male, 59% female. All participants clinically stable at start of study, mean (SD) baseline FEV1 % predicted 64.9 (13.6) for the mannitol group and 64.4 (11.8) for the control group. 46.2% received concomitant dornase alfa. No hypertonic saline within 2 weeks of start of study. Group A (received mannitol first, then control) and group B (received control first, then mannitol).
Interventions	Treatment: inhaled dry powder mannitol 420 mg 2x daily,14 x 30 mg capsules. Fine particle fraction > 40%. Children < 12 years: administered via low resistance dry powder inhaler RS01 Plastiape, Osnago, Italy. Children ≧ 12 years and adults: administered via higher resistance dry powder inhaler, Inhalator, Boeringer‐Ingelheim, Ingelheim, Germany. Control: non‐respirable mannitol with a fine particle fraction < 2%. Identical in appearance and taste to mannitol capsules. 14 capsules 2x daily using same inhaler devices as for mannitol.
Outcomes	Primary outcome: FEV1 (change over 2 weeks). Secondary outcomes: FEF25-75; FVC; FEV1/FVC ratio and PEF; HRQoL scores (using age appropriate CFQ‐R, including burden of treatment); respiratory symptoms; sputum microbiology and safety.
Funding Source	Supported by Pharmaxis Limited and and an employee of Pharmaxis was among the authors.
Conflicts of Interest	Conflicts of interest of all authors outlined in the manuscript
Notes	Some additional data supplied by Pharmaxis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation code externally generated in small block design stratified to site and dornase alfa.
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding (performance bias and detection bias) Participants	Low risk	Described as double‐blind; mannitol and control capsules identical in taste and appearance. Same inhaler devices for mannitol and control.
Blinding (performance bias and detection bias) Clinicians	Low risk	Described as double‐blind; mannitol and control capsules identical in taste and appearance. Same inhaler devices for mannitol and control.
Blinding (performance bias and detection bias) Outcome assessors	Low risk	Described as double‐blind, it was stated that study staff and investigators were blinded. Same inhaler devices for mannitol and control. Pharmaxis confirmed the statistician is part of the study staff and therefore was blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	56 days follow‐up data not reported. 4 participants withdrew and one of these was due to "Unexplained withdrawal" by physician. Unclear how many participants were evaluated for each outcome.
Selective reporting (reporting bias)	Unclear risk	All outcomes specified were reported, but little detail.
Other bias	High risk	Participants underwent a mannitol tolerance test at screening; those who failed the test or in whom the test was incomplete were not entered into the study and thus, the study population included only those with CF who passed the tolerance test and not all potential participants with CF. Sponsored by Pharmaxis; authors or study staff worked for Pharmaxis or had financial interest.