Dingemans 2018.

Study characteristics
Methods	RCT. Pilot study. Cross‐over design. Three treatments arms: AD alone, AD in combination with IPV at medium (200bpm) frequency or AD in combination with IPV at high (400bpm) frequency. Patients were randomised to receive a different treatment during each of three consecutive hospital admissions for IV antibiotics.  Length of hospital stay reflected time in each treatment arm, which ranged from 5‐10 days. Each treatment technique was separated by a minimum washout period of 3 months, during which each participant reverted to using AD as their standard ACT.  The first treatment was preceded by at least 3 months of daily AD routines. The participants acted as their own control group. Single centre. Location: Belgium.
Participants	4 CF adults, chronically colonised with P aeruginosa and receiving inpatient IV antibiotics for respiratory infection.  Age range: 20‐34yrs. Gender split: 1 male, 3 female. FEV1 range: 24‐60%. FVC range: 49‐75%.
Interventions	Treatment 1: 2x daily AD treatment sessions (30 minutes each). Treatment 2: 2x daily AD combined with IPV at medium (200 bpm) frequency (30 minutes each). Treatment 3: 2x daily AD combined with IPV at high (400 bpm) frequency (30 minutes each).
Outcomes	FEV1 percentage change from baseline FVC percentage change from baseline This paper also considered the effect of IPV treatments on bacterial load in CF sputum and P aeruginosa gene expression analysis, but these outcome measures were beyond the scope of this review.
Notes	FEV1 and FVC outcomes were measured at three different time points during inpatient treatments (day 1, day 3 ‐ 5 and day 5 ‐ 10).  Time points varied both between participants and hospital admissions. The study authors were contacted and kindly provided us with additional unpublished data for each of the four participants: all FEV1 and FVC values (% predicted) and the specific time points at which they were measured, together with the number of days spent in each of the 3 treatment arms. No raw data on bacterial load and gene expression given ‐ only what was displayed in graphs.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The paper states that "A randomized cross‐over study was conducted."  The authors were contacted and kindly provided additional unpublished information, stating that "AD, IPV 200, and IPV 400 were assigned a treatment number (1, 2 or 3) and each patient was given a random order of treatments. Ten index cards with a random order of treatments were enclosed in sealed envelopes. For patient 1 we took the first envelope, for patient 2 we took the second, etc."
Allocation concealment (selection bias)	Low risk	The authors were contacted and kindly provided additional unpublished information, stating that "AD, IPV 200, and IPV 400 were assigned a treatment number (1, 2 or 3) and each patient was given a random order of treatments. Ten index cards with a random order of treatments were enclosed in sealed envelopes. For patient 1 we took the first envelope, for patient 2 we took the second, etc."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Neither participants nor physiotherapy personnel were blinded to the physiotherapy techniques under study. As it is not possible to blind by design, the risk of bias is deemed to be low.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The paper states that lab staff analysing the sputum samples were blinded. The study authors were contacted and provided this review with additional unpublished information, stating that: "Spirometry technicians were blinded. Statistics were not blindly performed, but performed when all data were obtained."
Incomplete outcome data (attrition bias) All outcomes	High risk	Data missing for some participants; some of the outcomes stated in the protocol were not reported in the published pilot study. Withdrawals from the study were not reported as withdrawals. The study authors were contacted for clarification on this point and stated  that "we actually performed the clinical trial including 8 patients originally (4 chronically colonized with P. aeruginosa vs 4 not colonized with P. aeruginosa). However, some of the patients that were not colonized with P. aeruginosa dropped out of the trial after only receiving 1 treatment, making it difficult to statistically compare the 3 treatments. Because of this, we focused on the 4 patients chronically colonized with P. aeruginosa, for which sufficient data could be collected to draw conclusions supported by statistical analysis."
Selective reporting (reporting bias)	Unclear risk	Not all outcomes in the protocol were reported in the pilot study and some of the participants' outcomes were missing.  Out of a small sample size of four patients, lung function data relating to one of the treatment arms were not available for two of these and, together with the bacterial count for one patient, were not reported in the published paper. Following correspondence with the study authors for additional information, they clarified that "some participants did not complete all 3 treatments, due to their participation in other clinical trials" and that for the latter patient "bacterial loads... were not determined because of technical issues."
Other bias	High risk	Two out of the four participants only took part in 2 of the 3 treatment arms.  Another participant received IPV high (400 bpm) frequency treatment twice and only one data set was presented.  Treaments under review were administered during inpatient hospital admissions, with different IV antibiotic combinations and varying lengths of stay.  As such, data collection points varied between patients and hospital admissions.