Table 4.

Summary of patient-reported outcomes assessed in key phase III^* and IV^† studies.

	Patient-reported outcome	Key finding
TSQM (median scores for domains): TIP versus TIS
EAGER (phase III)	Effectiveness: 74.8 versus 65.4 (difference 9.36, SE = 1.46; p = 0.0001) Global satisfaction: 76.2 versus 71.0 (difference 5.20, SE = 1.66; p = 0.002) Convenience: 82.7 versus 58.4 (difference 24.35, SE = 1.55; p < 0.0001) Side effects: 92.1 versus 92.6 (difference 0.50, SE = 1.22; p = 0.6833)	Overall, patients showed greater treatment satisfaction with TIP
2403 (phase IV)	TIS/TIP arm: Cycle 2 (after crossover to TIP): Median scores were improved from cycle 1 only for convenience (13.9 units) COLI/TIP arm: Cycle 2 (after crossover to TIP): Median scores were improved from cycle 1 [effectiveness (8.3 units), convenience (22.2 units), and global satisfaction (10.7 units)] TIP/TIP arm: Effectiveness and convenience scores: cycle 2 scores were unchanged from those of cycle 1 Global satisfaction: median score decreased slightly (7.2 units) in cycle 2 from cycle 1 Side-effects: maximum score (100 units on a scale of 0–100 ) for all the treatment arms in both cycles, meaning patients did not report experiencing side effects from their medication
FREE (phase IV)	Convenience domain: domain with highest improvement (enrollment: 74.2 ± 17.1; end of study: 77.8 ± 15.9 at the end of study); mean increase: 2.8 ± 17.9 (95% CI: −2.4 to 8.0) Efficacy domain: slight increase following the introduction of TIP (enrollment: 63.6 ± 19.8; end of study: 67.5 ± 15.1 at the end of study); mean increase: 1.8 ± 22.4 (95% CI: –4.6 to 8.2) Global satisfaction and side effects domains revealed no significant changes during the study when compared with baseline
GB01 (phase IV)	All four domains were scored high, indicating greater patient satisfaction Mean increase of scores in four domains: Effectiveness: 5.0 points (SD: ± 24.1) at 1 month and 10.2 points (SD: ± 19.9) at 5 months Side effects: 5.2 points (SD: ± 18.7) at 1 month and 5.6 points (SD: ± 15.9) at 5 months Convenience: 25.6 points (SD: ± 23.5) at 1 month and 29.7 (SD: ± 24.6) points at 5 months global satisfaction: 12.9 points (SD: ± 23.6) at 1 month and 19.9 points (SD: ± 22.9) at 5 months
ACCEPtance (median scores for domains)
2403 (phase IV)	TIS/TIP arm: Cycle 2: Median scores were improved from cycle 1 (visit 3) for the domains of medication inconvenience (10 units), long-term treatment (8.3 units), and regime constraints (10 units) Median score for the domain of side effects reached the maximum satisfaction level (on a scale of 100 units) in both cycle 1 and cycle 2Median scores decreased in cycle 2 for the domains of effectiveness and general COLI/TIP arm: Cycle 2: Median scores were improved for the domains of medication inconvenience (20 units), long-term treatment (12.5 units), and regime constraints (10 units) Median scores decreased in cycle 2 for the domain of side effects TIP/TIP arm: Cycle 2: Median scores were improved from cycle 1 for the domains of medication inconvenience (5 units), regime constraints (2.5 units), effectiveness (16.7 units), and general (8.3 units) The median score for the domain of side effects was the same in both cycles (90 units on a 0–100 scale) Median score for the domain of long-term treatment remained the same in both cycles (66.7 units on a 0–100 scale)	After crossover to TIP (cycle 2), TIS/TIP and COLI/TIP arms showed greater acceptance for TIP
Patient preference
2403 (phase IV)	The majority of patients demonstrated either ‘strong’ or ‘somewhat’ treatment preference for TIP in the TIS/TIP (9 out of 12 patients, 75.0%) and COLI/TIP (18 out of 23 patients, 78.3%) arms The majority (⩾78.3%) of patients demonstrated preference for TIP for the efficiency of saving time, portability, simplicity, and other advantages	Patient preference was high for TIP
FR01	12-month follow up (TIP versus previous treatments): 61 (88.4%) versus 4 (5.8%) Patient preference for TIP was higher in adult than in younger patients: 48 (87.3%) versus 12 (66.7%)
ITA-CFq
FREE (phase IV)	Adherence to TIP at the end of cycle 3 as measured by ITA-CFq scores was high: Enrollment: mean compliance score to nebulized antibiotics: 7.8 ± 3.2 (95% CI: 6.9–8.7) Follow-up visits 1 and 2: mean compliance scores to TIP: 9.4 ± 1.2 (95% CI: 9.0–9.7) and 9.5 ± 1.2 (95% CI: 9.1–9.8), respectively After initiation of TIP, treatment adherence increased by 20.5% at the first follow up at 3 months (9.4 ± 1.2), then remained stable up to the end of study (9.5 ±1.2)	Patients were more compliant with TIP
CFQ-R
FREE (phase IV)	No substantial impact of TIP was observed in terms of QoL, as assessed by the CFQ-R All domains remained roughly unchanged from baseline to study end
GB01 (phase IV)	Mean increase from baseline in CFQ-R treatment burden domain scores‡ at 1 and 5 months after initiation of TIP: 7.9 points (SD: ± 19.2) at 1 month (p < 0.01) and 6.5 points (SD: ± 20.3) at 5 months
Morisky score
FR01 (phase IV)	Adherence to TIP as measured by the Morisky score: Baseline visit: 50.0% of patients were compliant with previous inhaled treatment; mean Morisky score was 2.5 (±1.2) 12-month follow up: 59.6% of patients were compliant with TIP treatment (95% CI: 45.3–72.4%); mean Morisky score was 2.7 (SD: ± 1.0) At 12-month follow up, adherence was better in children and teenagers compared with adults: 80%, 75%, and 48.3% of adherent patients with mean Morisky scores of 3.1 (SD: ± 0.7), 3.0 (SD: ± 0.8), and 2.5 (SD: ± 1.1), respectively
Patient’s diary
FREE (phase IV)	Average number of missed antibiotic doses per patient during the past week was 0.5 ± 0.7 at first cycle, 0.4 ± 0.5 at second cycle, and 0.4 ± 0.8 at third cycle (the average number of antibiotic capsules used for each dose was always 4)

^*Konstan et al. 2011a. ^† Data on file. ^‡Domains are scored out of 100 with a higher score indicating greater patient satisfaction.

AEs, adverse events; CFQ-R, cystic fibrosis questionnaire: revised; CI, confidence interval; COLI, colistimethate sodium; ITA-CFq, Italian Treatment Adherence Cystic Fibrosis Questionnaire; QoL, quality of life; SE, standard error; SD, standard deviation; TIP, tobramycin inhalation powder; TIS, tobramycin inhalation solution; TSQM, treatment satisfaction questionnaire for medication.