Input parameters of the model per person-year
| Parameter | Base value | Probability distribution | Source | ||||
| GOLD II | GOLD III | GOLD IV | GOLD II | GOLD III | GOLD IV | ||
| Initial distributions | 0.26 | 0.4 | 0.34 | NA | NA | NA | Albert et al 4 |
| Baseline age | 65 | NA | Albert et al 4 | ||||
| Transition probability (95% CI) | Hoogendoorn et al 9 | ||||||
| Ex-smokers | 0.034 (0.033 to 0.035) | 0.030 (0.028 to 0.031) | NA | Beta (5703, 162 046) | Beta (1372, 44 377) | NA | |
| Current smokers | 0.037 (0.036 to 0.038) | 0.031 (0.029 to 0.032) | NA | Beta (6206, 161 543) | Beta (1418, 44 332) | NA | |
| Exacerbation rate in the reference group (95% CI) | Hoogendoorn et al 10 | ||||||
| Total exacerbations | 1.17 (0.93 to 1.50) | 1.61 (1.51 to 1.74) | 2.10 (1.51 to 2.94) | Lognormal (0.16, 0.13) | Lognormal (0.48, 0.04) | Lognormal (0.74, 0.17) | |
| Severe exacerbations | 0.16 (0.07 to 0.33) | 0.22 (0.20 to 0.23) | 0.28 (0.14 to 0.63) | Lognormal (−1.83, 0.37) | Lognormal (−1.51, 0.02) | Lognormal (−1.27, 0.40) | |
| Rate ratio of exacerbation (total and severe) by 12-month history pattern (95% CI) | ECLIPSE study32
(online supplemental appendix 4) | ||||||
| No exacerbations in the first year | Total: 0.16 (0.14 to 0.17) | Total: normal (0.160, 0.007) | |||||
| Severe: 0.16 (0.12 to 0.20) | Severe: normal (0.16, 0.02) | ||||||
| ≥1 moderate/severe exacerbations in the first year | 1 (Reference) | NA | |||||
| ≥2 moderate or ≥1 severe exacerbation in the first year | Total: 1.25 (1.16 to 1.33) | Normal (1.25, 0.04) | |||||
| Severe: 1.36 (1.17 to 1.58) | Normal (1.36, 0.10) | ||||||
| ≥2 moderate/severe exacerbations in the first year | Total: 1.30 (1.20 to 1.40) | Normal (1.30, 0.05) | |||||
| Severe: 1.26 (1.07 to 1.48) | Normal (1.26, 0.10) | ||||||
| Relative risk of exacerbation in the treatment group compared with the control group (95% CI) | |||||||
| Total | 0.73 (0.63 to 0.84) | Lognormal (−0.31, 0.07) | Albert et al 4 | ||||
| Ex-smokers | 0.65 (0.55 to 0.77) | Lognormal (−0.43, 0.08) | Han et al 25 | ||||
| Current smokers | 0.99 (0.71 to 1.38) | Lognormal (−0.01, 0.17) | Han et al 25 | ||||
| Decline in treatment effect | RR0
exp (– k * (year – 1))
RR0: first-year effect k=0.22 | Fixed | Pomares et al
13
(online supplemental appendix 1) | ||||
| Rate of mortality due to exacerbations (95% CI) | 0.156 (0.109 to 0.203) | Beta (35.6, 192.4) | Hoogendoorn et al 11 | ||||
| Hazard ratio of cardiovascular death in the first 5 days (95% CI) | 2.88 (1.79 to 4.63) | Lognormal (1.06, 0.24) | Ray et al 6 | ||||
| Relative risk of hearing loss due to azithromycin (95% CI) | 1.168 (1.030 to 1.325) | Lognormal (0.15, 0.06) | Li et al 5 | ||||
| Annual incidence of hearing loss (95% CI) | 0.023 (0.011 to 0.035) | Normal (0.023, 0.006) | Lin et al
17
(online supplemental appendix 2) | ||||
| Prevalence of GI symptoms in the population | 0.332 (0.326 to 0.333) | Beta (28 945, 58 768) | Almario et al 18 | ||||
| Relative risk of GI symptoms due to azithromycin (95% CI) | 1.187 (0.761 to 1.849) | Lognormal (0.17, 0.22) | Li et al 5 | ||||
| Baseline utility (EQ-5D) (95% CI) | 0.787 (0.771 to 0.802) | 0.750 (0.731 to 0.768) | 0.647 (0.598 to 0.695) | Beta (2251, 609.4) | Beta (1666, 555.5) | Beta (245.7, 134.1) | Rutten-van Mölken et al 33 |
| Decrease in utility due to exacerbations (95% CI) | Sadatsafavi et al
34
(online supplemental appendix 3) | ||||||
| Mild and moderate | 0.015 (0.002 to 0.040) | 0.049 (0.020 to 0.090) | 0.049 (0.020 to 0.090) | Beta (2.08, 132.50) | Beta (7.19, 140.30) | Beta (7.19, 140.30) | |
| Severe and very severe | 0.068 (0.035 to 0.110) | 0.065 (0.030 to 0.100) | 0.065 (0.030 to 0.100) | Beta (11.92, 162.60) | Beta (12.7, 182.1) | Beta (12.7, 182.1) | |
| Decrease in utility due to hearing loss (95% CI) | 0.187 (0.167 to 0.207) | Beta (6.92, 30.08) | NICE Guideline21 | ||||
| Utility improvement due to hearing aids (95% CI) | 0.060 (0.044 to 0.073) | Normal (0.060, 0.006) | Barton et al 35 | ||||
| Decrease in utility due to the GI symptoms (95% CI) | 0.026 (0.024 to 0.028) | Beta (66 343, 2 475 535) | Sullivan and Ghushchyan36
(online supplemental appendix 3) | ||||
| Discount rate | 3% | NA | Sanders et al 8 | ||||
ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; EQ-5D, EuroQol 5-Dimensional ; GI, gastrointestinal; GOLD, Global Initiative for Chronic Obstructive Lung Disease; NA, not applicable; NICE, National Institute for Health and Care Excellence.