Table 1.
Key parameter inputs to the economic model and the ranges of the sensitivity analyses.
| Baseline value | Lower limit | Upper limit | Distributiona | Source | |
|---|---|---|---|---|---|
| Drug cost (per year), $b | |||||
| NAC (600 mg, tid) | 11,232 | 8,424c | 14,040c | Gamma (11,232, 2808) | CMS 202250 |
| Ambrisentan (10 mg, qd) | 110,783 | 83,087c | 138,479c | Gamma (110,783, 27,696) | CMS 202250 |
| Bosentan (125 mg, bid) | 250,200 | 187,650c | 312,750c | Gamma (250,200, 62,550) | CMS 202250 |
| Imatinib (600 mg, qd) | 570,910 | 428,182c | 713,637c | Gamma (570,910, 142,727) | CMS 202250 |
| Macitentan (10 mg, qd) | 103,820 | 77,865c | 129,776c | Gamma (103,820, 25,956) | CMS 202250 |
| Nintedanib (150 mg, bid) | 106,632 | 79,974c | 133,290c | Gamma (106,632, 26,658) | CMS 202250 |
| Pirfenidone (400 mg, tid) | 23,198 | 17,399c | 28,998c | Gamma (23,198, 5800) | CMS 202250 |
| Sildenafil (20 mg, tid) | 46,148 | 34,611c | 57,686c | Gamma (46,148, 11,538) | CMS 202250 |
| Colchicine (1 mg, qd) | 1858 | 1,393c | 2,322c | Gamma (1,858, 464) | CMS 202250 |
| Cyclophosphamide (100 mg, qd) | 44,856 | 33,642c | 56,070c | Gamma (44,856, 11,214) | CMS 202250 |
| Etanercept (2.5 mg, biw) | 767,902 | 575,926c | 959,877c | Gamma (767,902, 191,975) | CMS 202250 |
| IFN-γ (200ug, tid) | 98,606 | 73,954c | 123,257c | Gamma (98,606, 24,651) | CMS 202250 |
| Warfarin (2.5 mg, qd) | 774 | 581c | 968c | Gamma (774, 194) | CMS 202250 |
| Follow-up cost (per year), $b | |||||
| Acute exacerbation | 14,731 | 11,048c | 18,414c | Gamma (14,731, 3683) | Yu 201652 |
| Oxygen therapyd | 6978 | 5,234c | 8,723c | Gamma (6,978, 1745) | Medicare PFS51 (CPT4: 94,453) |
| Pulmonary function testd | 132 | 99c | 165c | Gamma (132, 33) | Medicare PFS51 (CPT4: 94,727) |
| CT chestd | 140 | 105c | 175c | Gamma (140, 35) | Medicare PFS51 (CPT4: 771,250) |
| Inspectiond | 107 | 81c | 134c | Gamma (107, 27) | Medicare PFS51 (CPT4: G0463) |
| Health utilitiese | |||||
| Progression-free survival (QALYs) | 0.88 | 0.75f | 0.93f | Beta (0.88, 0.09) | Mohindru 2020,58 King 2008,59 Behr 2019,60 Richeldi 201413 |
| Progressed disease (QALYs) | 0.82 | 0.74f | 0.87f | Beta (0.82, 0.06) | Mohindru 202058 |
| Acute exacerbation (QALYs) | 0.60 | 0.44f | 0.76f | Beta (0.60, 0.16) | Mohindru 202058 |
| Progression-free survival (DALYs) | 0.02 | 0.01f | 0.03f | Beta (0.02, 0.01) | GBD 201745 |
| Progressed disease (DALYs) | 0.22 | 0.15f | 0.31f | Beta (0.22, 0.08) | GBD 201745 |
| Acute exacerbation (DALYs) | 0.41 | 0.27f | 0.56f | Beta (0.41, 0.14) | GBD 201745 |
| Effectivenessg | |||||
| All-cause mortality | |||||
| Acute exacerbation | 0.62 | 0.49f | 0.83f | Beta (0.62, 0.17) | Arai 2017,61 Aso 2019,62 Hozumi 2019,63 Kawamura 201764 |
| NAC | 0.02 | 0.01f | 0.13f | Beta (0.02, 0.01) | NMA Fig. 2B |
| Ambrisentan | 0.08 | 0.07f | 0.09f | Beta (0.08, 0.02) | NMA Fig. 2B |
| Bosentan | 0.04 | 0.03f | 0.04f | Beta (0.04, 0.03) | NMA Fig. 2B |
| Imatinib | 0.04 | 0.02f | 0.11f | Beta (0.04, 0.01) | NMA Fig. 2B |
| Macitentan | 0.29 | 0.24f | 0.32f | Beta (0.29, 0.04) | NMA Fig. 2B |
| Nintedanib | 0.13 | 0.07f | 0.29f | Beta (0.05, 0.01) | NMA Fig. 2B |
| Pirfenidone | 0.13 | 0.03f | 0.41f | Beta (0.07, 0.01) | NMA Fig. 2B |
| Sildenafil | 0.08 | 0.04f | 0.11f | Beta (0.14, 0.02) | NMA Fig. 2B |
| placebo or no treatment | 0.18 | 0.01f | 0.81f | Beta (0.16, 0.01) | NMA Fig. 2B |
| NAC + Pirfenidone | 0.04 | 0.02f | 0.06f | Beta (0.04, 0.01) | NMA Fig. 2B |
| Nintedanib + sildenafil | 0.10 | 0.09f | 0.11f | Beta (0.10, 0.02) | NMA Fig. 2B |
| Colchicine | 0.41 | 0.39f | 0.43f | Beta (0.41, 0.09) | NMA Fig. 2B |
| Cyclophosphamide | 0.47 | 0.40f | 0.54f | Beta (0.48, 0.04) | NMA Fig. 2B |
| Etanercept | 0.02 | 0.01f | 0.03f | Beta (0.02, 0.02) | NMA Fig. 2B |
| IFN-γ | 0.16 | 0.15f | 0.17f | Beta (0.17, 0.02) | NMA Fig. 2B |
| Warfarin | 0.19 | 0.16f | 0.22f | Beta (0.19, 0.09) | NMA Fig. 2B |
| Pirfenidone + sildenafil | 0.17 | 0.14f | 0.20f | Beta (0.17, 0.04) | NMA Fig. 2B |
| Acute exacerbation rate | |||||
| NAC | 0.04 | 0.01f | 0.28f | Beta (0.04, 0.01) | NMA Fig. 2D |
| Ambrisentan | 0.13 | 0.11f | 0.15f | Beta (0.13, 0.02) | NMA Fig. 2D |
| Bosentan | 0.11 | 0.03f | 0.14f | Beta (0.11, 0.01) | NMA Fig. 2D |
| Imatinib | 0.09 | 0.03f | 0.14f | Beta (0.09, 0.01) | NMA Fig. 2D |
| Macitentan | 0.06 | 0.05f | 0.07f | Beta (0.06, 0.02) | NMA Fig. 2D |
| Nintedanib | 0.05 | 0.04f | 0.12f | Beta (0.05, 0.01) | NMA Fig. 2D |
| Pirfenidone | 0.11 | 0.02f | 0.42f | Beta (0.11, 0.01) | NMA Fig. 2D |
| Sildenafil | 0.06 | 0.03f | 0.31f | Beta (0.06, 0.02) | NMA Fig. 2D |
| placebo or no treatment | 0.08 | 0.02f | 0.68f | Beta (0.08, 0.01) | NMA Fig. 2D |
| NAC + Pirfenidone | 0.03 | 0.01f | 0.03f | Beta (0.03, 0.02) | NMA Fig. 2D |
| Nintedanib + sildenafil | 0.09 | 0.07f | 0.21f | Beta (0.09, 0.02) | NMA Fig. 2D |
| Colchicine | 0.25 | 0.08f | 0.14f | Beta (0.25, 0.01) | NMA Fig. 2D |
| Cyclophosphamide | 0.25 | 0.19f | 0.31f | Beta (0.25, 0.01) | NMA Fig. 2D |
| Etanercept | 0.63 | 0.51f | 0.75f | Beta (0.63, 0.07) | NMA Fig. 2D |
| IFN-γ | 0.05 | 0.05f | 0.25f | Beta (0.05, 0.01) | NMA Fig. 2D |
| Warfarin | 0.29 | 0.23f | 0.35f | Beta (0.29, 0.01) | NMA Fig. 2D |
| Pirfenidone + sildenafil | 0.11 | 0.08f | 0.14f | Beta (0.11, 0.03) | NMA Fig. 2D |
| Disease progression rate | |||||
| NAC | 0.11 | 0.02f | 0.36f | Beta (0.11, 0.01) | NMA Fig. 2F |
| Ambrisentan | 0.27 | 0.22f | 0.31f | Beta (0.27, 0.02) | NMA Fig. 2F |
| Bosentan | 0.26 | 0.16f | 0.31f | Beta (0.26, 0.02) | NMA Fig. 2F |
| Imatinib | 0.25 | 0.21f | 0.29f | Beta (0.25, 0.05) | NMA Fig. 2F |
| Macitentan | 0.21 | 0.18f | 0.25f | Beta (0.21, 0.04) | NMA Fig. 2F |
| Nintedanib | 0.49 | 0.29f | 0.71f | Beta (0.49, 0.01) | NMA Fig. 2F |
| Pirfenidone | 0.15 | 0.02f | 0.44f | Beta (0.15, 0.05) | NMA Fig. 2F |
| Sildenafil | 0.07 | 0.03f | 0.53f | Beta (0.07, 0.02) | NMA Fig. 2F |
| Placebo or no treatment | 0.29 | 0.04f | 0.72f | Beta (0.29, 0.01) | NMA Fig. 2F |
| NAC + Pirfenidone | 0.25 | 0.13f | 0.65f | Beta (0.25, 0.04) | NMA Fig. 2F |
| Nintedanib + sildenafil | 0.26 | 0.21f | 0.31f | Beta (0.26, 0.04) | NMA Fig. 2F |
| Colchicine | 0.56 | 0.30f | 0.79f | Beta (0.56, 0.11) | NMA Fig. 2F |
| Cyclophosphamide | 0.20 | 0.15f | 0.25f | Beta (0.20, 0.05) | NMA Fig. 2F |
| Etanercept | 0.07 | 0.04f | 0.08f | Beta (0.07, 0.04) | NMA Fig. 2F |
| IFN-γ | 0.09 | 0.08f | 0.25f | Beta (0.09, 0.01) | NMA Fig. 2F |
| Warfarin | 0.25 | 0.21f | 0.29f | Beta (0.25, 0.05) | NMA Fig. 2F |
| Pirfenidone + sildenafil | 0.73 | 0.66f | 0.80f | Beta (0.73, 0.05) | NMA Fig. 2F |
| Other | |||||
| Age, years | 67.30 | 66.54h | 68.04h | Normal (67.30, 0.75) | Supplemental Table S1 |
| Discount rate, % | 0.05 | 0.00f | 0.08f | Normal (0.05, 0.04) | Sanders 2016,47 Hultkrantz 202148 |
| Follow-up period, years | 12.00 | 11.00h | 17.00h | Normal (12.00, 3.21) | Supplemental Table S1 |
| Expected life, years | 78.5 | NA | NA | Uniform (78.5) | WHO 202243 |
Abbreviations: NA, Not applicable; IFN-γ, Interferon-γ; NAC, N-acetylcysteine; qd, Once daily; bid, Twice a day; tid, Three times a day; biw, twice a week; NMA, Network meta-analysis; CMS, Centers for Medicare & Medicaid Services; PFS, Physician fee schedule; GBD, Global Burden of Disease; WHO, World Health Organization; QALY, Quality-adjusted life year; DALY, Disability-adjusted life year.
a
Distributions were presented as (mean, standard deviation).
b
All costs estimates were inflated to 2022 US dollars using the Consumer Price Index.
c
Baseline values as the mean; plus or minus 25% from mean values were adopted to estimate standard deviation.
d
Inspection and pulmonary function test were set as three times per year; CT chest was set as one time per year; oxygen therapy was set as twice a week.
e
The health utilities are values that vary between 0 and 1, and have no units.
f
Possible maximum and minimum values.
g
The transition probability and absolute risk for all-cause mortality, acute exacerbation and disease progression per year, were derived from our network meta-analysis, as shown in Fig. 2B, D and F.
h
Values with 95% confidence intervals.