Figures
- FIGURE 1
A Markov model for ivacaftor in patients with cystic fibrosis. FEV1: forced expiratory volume in 1 s.
- FIGURE 2
One-way uncertainty of inputs on a) incremental life expectancy and b) incremental quality-adjusted life-year. FEV1: forced expiratory volume in 1 s.
- FIGURE 3
a) Expected survival and b) expected quality-adjusted survival given age comparing cystic fibrosis (CF) patients with the non-CF population.
Tables
- TABLE 1
Model inputs
Base-case value (range) Distribution Reference Efficacy of ivacaftor Patient Aged 6–11 years 10.0 (–) [5] Aged ≥12 years 10.5 (–) [6] Relative risk of pulmonary exacerbation Aged 6–11 years 1.0 (–) [5] Aged ≥12 years 0.43 (0.27–0.59) Log-normal [6] Relative risk of pulmonary exacerbation hospitalisation Aged 6–11 years 1.0 (–) [5] Aged ≥12 years 0.64 (0.40–1.00) Log-normal [6] Average FEV1 % pred for moderate lung disease Aged 6–11 years 30.0 (20.20–39.80) Gamma Assumption Aged ≥12 years 55.0 (45.20–64.80) Normal Assumption Transition probability Mild to moderate lung disease Vary based on age (–) Beta [16] Mild to severe lung disease Vary based on age (–) Beta [16] Mild to lung transplantation Vary based on age (–) Beta [16] Moderate to severe lung disease Vary based on age (–) Beta [16] Moderate to lung transplantation Vary based on age (–) Beta [16] Severe lung disease to lung transplantation Vary based on age (–) Beta [16] Mortality data Mild lung disease to death Age-specific mortality (–) [17] Moderate lung disease to death 0.030 (0.025–0.375) Uniform (±25%) [18] Severe lung disease to death 0.070 (0.053–0.088) Uniform (±25%) [18] Lung transplantation to death 0.152 (0.139–0.165) Beta [19] Healthcare resource utilisation Mild lung disease Hospitalisation 0.20 (0–0.894) Gamma [21] Outpatient hospitalisation 0.10 (0–0.447) Gamma [21] Clinic visits 7.00 (0–16.690) Gamma [21] Probability of patients using pancreatic enzymes 0.89 (–) [21] Probability of patients using intravenous antibiotics 0.02 (–) [21] Probability of patients using DNase 0.36 (–) [21] Moderate lung disease Hospitalisation 0.40 (0–1.488) Gamma [21] Outpatient hospitalisation 0.30 (0–1.541) Gamma [21] Clinic visits 7.00 (0–15.790) Gamma [21] Probability of patients using pancreatic enzymes 0.84 (–) [21] Probability of patients using intravenous antibiotics 0.49 (–) [21] Probability of patients using DNase 0.72 (–) [21] Severe lung disease Hospitalisation 1.70 (0–4.399) Gamma [21] Outpatient hospitalisation 1.40 (0–5.058) Gamma [21] Clinic visits 10.00 (0–22.100) Gamma [21] Probability of patients using pancreatic enzymes 0.95 (–) [21] Probability of patients using intravenous antibiotics 0.71 (–) [21] Probability of patients using DNase 0.71 (–) [21] Probability of double lung transplantation 0.964 (0.960–0.968) Beta [24] Cost US$ Mild lung disease Hospitalisation 2406.61 (0–18 522.86) Gamma [21] Clinic visit 2406.61 (0–6730.48) Gamma [21] DNase 3008.26 (0–13 228.32) Gamma [21] Outpatient antibiotics 802.20 (0–3946.84) Gamma [21] Pancreatic enzymes 3008.26 (0–8904.45) Gamma [21] Other medications 1002.75 (0–3361.23) Gamma [21] Moderate lung disease Hospitalisation 7821.47 (0–60 101.04) Gamma [21] Clinic visit 2206.06 (0–8310.82) Gamma [21] DNase 5214.32 (0–20 568.48) Gamma [21] Outpatient antibiotics 1604.41 (0–13 613.38) Gamma [21] Pancreatic enzymes 3008.26 (0–7909.72) Gamma [21] Other medications 1203.30 (0–2374.52) Gamma [21] Severe lung disease Hospitalisation 56 154.20 (0–224 392.18) Gamma [21] Clinic visit 6217.07 (0–17 616.37) Gamma [21] DNase 10 027.54 (0–31 646.90) Gamma [21] Outpatient antibiotics 9425.88 (0–53 843.85) Gamma [21] Pancreatic enzymes 2406.61 (0–7516.64) Gamma [21] Other medications 2807.71 (0–13 420.85) Gamma [21] Single lung 30 days pre-transplant 10 889.39 (8167.05–13 611.74) Uniform (±25%) [22] Procurement 77 283.01 (57 962.26–96 603.76) Uniform (±25%) [22] Hospital transplant admission 320 232.87 (240 174.66–400 291.09) Uniform (±25%) [22] Physician fee during transplantation 35 416.97 (26 562.73–44 271.22) Uniform (±25%) [22] 180 days post-transplantation 124 435.16 (93 326.37–155 543.95) Uniform (±25%) [22] Outpatient immunosuppressant and other medication 25 056.19 (18 792.14–31 320.23) Uniform (±25%) [22] Follow-up in months 7–12 after transplantation 65 459.75 (49 094.81–81 824.69) Uniform (±25%) [23] Follow-up for the following year 108 899.04 (81 674.28–136 123.80) Uniform (±25%) [23] Double lung 30 days pre-transplant 22 624.57 (16 968.43–28 280.72) Uniform (±25%) [22] Procurement 95 467.25 (71 600.43–119 334.06) Uniform (±25%) [22] Hospital transplant admission 484 736.79 (363 522.59–605 920.98) Uniform (±25%) [22] Physician fee during transplantation 59 521.67 (44 641.25–74 402.08) Uniform (±25%) [22] 180 days post-transplantation 150 760.01 (113 070.01–188 450.02) Uniform (±25%) [22] Out-patient immunosuppressant and other medication 29 813.69 (22 360.27–37 267.11) Uniform (±25%) [22] Follow-up in months 7–12 after transplantation 65 459.75 (49 094.81–81 824.69) Uniform (±25%) [23] Follow-up for the following year 108 899.04 (81 674.28–136 123.80) Uniform (±25%) [23] Ivacaftor per tablet 426.72 (320.04–533.40) Uniform (±25%) [14] Utility Patients with mild lung disease 0.803 (0.752–0.854) Beta [15] Patients with moderate lung disease 0.749 (0.708–0.790) Beta [15] Patients with severe lung disease 0.688 (0.639–0.737) Beta [15] Patients with lung transplantation 0.810 (0.732–0.888) Beta [15] FEV1: forced expiratory volume in 1 s.
- TABLE 2
Description of scenario analyses
Number Scenario Starting age years Description Treatment duration 1 Base-case 25 There is full efficacy of ivacaftor within first 2 years of treatment; after 2 years, there is 50% efficacy of ivacaftor Lifetime 2 Optimistic 25 There is full efficacy of ivacaftor though lifetime horizon Lifetime 3 Intermediate 25 There is full efficacy of ivacaftor within first 2 years of treatment; after 2 years, there is 66% efficacy of ivacaftor Lifetime 4 Conservative 25 There is full efficacy of ivacaftor within first 2 years of treatment; after 2 years, patients stop the treatment 2 years 5 6-year-old 6 There is full efficacy of ivacaftor within first 2 years of treatment; after 2 years, there is 50% efficacy of ivacaftor; the starting age of the cohort is 6 years Lifetime 6 9-year-old 9 There is full efficacy of ivacaftor within first 2 years of treatment; after 2 years, there is 50% efficacy of ivacaftor; the starting age of the cohort is 9 years Lifetime 7 12-year-old 12 There is full efficacy of ivacaftor within first 2 years of treatment; after 2 years, there is 50% efficacy of ivacaftor; the starting age of the cohort is 12 years Lifetime - TABLE 3
Results of base-case analysis
Usual care Ivacaftor plus usual care Incremental value# Receiving lung transplantation % 30.27 (27.26–34.31) 12.00 (8.87–16.18) −18.27 (−22.85– −13.63) Estimated life expectancy years 47.78 (46.66–49.21) 66.04 (61.35–70.11) 18.25 (13.71–22.20) Estimated quality-adjusted life-years 42.15 (41.15–43.37) 57.18 (53.02–61.19) 15.03 (11.13–18.73) Estimated lifetime cost US$ 1 130 184 (461 764–3 435 325) 4 504 768 (3 442 654–5 892 376) 3 374 584 (1 651 192–4 634 390) Data are presented as n (95% credible interval). All findings estimated based on the 25-year-old starting cohort. #: ivacaftor plus usual care versus usual care alone.
- TABLE 4
Results of scenario analysis
Scenario Incremental absolute percentage of receiving lung transplantation Additional life expectancy years Additional quality-adjusted life-years Incremental lifetime costs US$ Optimistic −29.53 (−26.44–−33.38) 30.59 (27.31–33.68) 25.64 (21.79–29.12) 3 540 660 (1 310 481–5 507 336) Intermediate −19.01 (−14.98–−23.01) 19.23 (15.15–22.54) 15.85 (12.37–18.93) 3 388 927 (1 451 385–4 817 945) Conservative −1.16 (−0.79–−1.59) 1.16 (0.91–1.49) 0.91 (0.71–1.18) 443 814 (−511 469–727 012) 6-year-old −18.50 (−22.05–−14.82) 18.09 (14.63–21.13) 14.92 (11.92–17.95) 3 740 480 (2 199 261–4 915 629) 9-year-old −19.74 (−15.91–−23.59) 19.30 (15.39–22.60) 15.83 (12.27–19.19) 3 517 034 (1 936 263–4 716 440) 12-year-old −20.04 (−15.72–−23.91) 19.56 (14.87–23.56) 16.03 (12.03–19.57) 3 455 593 (1 715 960–4 680 515) Data are presented as n (95% credible interval), ivacaftor plus usual care versus usual care alone.
Vol 47 Issue 6
Table of Contents
Forecasting US ivacaftor outcomes and cost in cystic fibrosis patients with the G551D mutation
