Inputs used to populate the microsimulation Markov model
| Parameter . | Value . | Reference . | ||
|---|---|---|---|---|
| Weight | Age-dependent Example: 30 years old: 89.30 kg | CDC NHANES22,23 | ||
| Cost-effectiveness threshold | $150 000 per added QALY | Institute for Clinical and Economic Review45 | ||
| Dosage | Supplemental Table 4 | BeneFix package insert46; ALPROLIX package insert47; Lexicomp9; Srivastava et al, 20205 | ||
| Costs Clotting factor (base case) Clotting factor (sensitivity analysis) Hospital bed/night Investigations Total joint replacement surgery (excluding factor concentrate) Gene therapy base case cost Gene therapy manufacturing cost (sensitivity analysis) Gene therapy follow-up cost | • SHL-FIX (BeneFix): $1.41/IU • EHL-FIX (ALPROLIX)*: $3.24/IU • SHL-FIX: $0.3/IU • EHL-FIX: $0.65/IU $995 Supplemental Tables 5 and 6 $13 187 $2 000 000 Total: $77 289 Direct costs: $48 917, indirect costs (58% of direct costs): $28 372 (Table 2) $9909 | WAC obtained from Redbook Online from Micromedex Solutions Knight et al, 200310; Farrugia et al, 201333; Miners, 200932; International Medical Products Price Guide (MSH) online database49 WHO-CHOICE Tool26 Centers for Medicare & Medicaid Services Online Database27 Medicare Procedure Price Lookup Online Database50; Centers for Medicare & Medicaid Services Online Database27 Cook et al, 202025; Wall Street Journal, 202024 Direct estimate of manufacturing cost from Children’s GMP, LLC, at SJCRH30 Centers for Medicare & Medicaid Services Online Database27 | ||
| Utilities On-demand Prophylaxis Gene therapy Joint damage decrement Minor bleed decrement Major bleed decrement Total joint replacement surgery decrement Injection decrement | 0.6705 – (0.0019 × age) 0.9378 – (0.0026 × age) Assumed to be the same as United States general population utilities (supplemental Figure 1) Depends on the year of joint damage; ranges between −0.14 and −0.38 (supplemental Table 4) −0.06 (for 1 wk) −0.18 (for 1 wk) −0.14 (for 1 mo) −0.0004 | Noone et al, 201351, Farrugia et al, 201333, Ara and Brazier, 201052 Szende et al, 201453 Carroll et al, 201954 Hoxer et al, 201955 Cook et al, 202025 | ||
| Transition probabilities/rates | ||||
| Annual bleeding rate (minor and major) Hospitalization Joint damage and total joint replacement surgery Mortality | Minor bleeds: • Prophylaxis: 1.2-5.5 • On-demand: 9.0-35.1 Major bleeds: • Prophylaxis: 0-0.2 • On-demand: 0.1-0.62 Post–gene therapy: No bleeding for 9 y, then minor bleeds occurred as the factor level dropped. Eventually, patient moved back to prophylaxis when the factor level dropped below 3 IU/dL (supplemental Table 4) Major bleed: hospitalization for 5 d per episode • Prophylaxis: None • On-demand/inhibitor: 1-3 per lifetime Supplemental Table 4 | Chen et al, 201756; Windyga et al, 201457; Collins et al, 201858; Kavakli et al, 201659; Powell et al, 201360; Lambert et al, 200761; Valentino et al, 201462; Santagostino et al, 201663; Shih et al, 201964; Ludlam et al, 200065; Soucie et al, 201816 BeneFix package insert46; ALPROLIX package insert47; Lexicomp9; Colowick et al, 200011; Knight et al, 200310 Castaman 201841; Lin et al, 201866 CDC WONDER,67 Hassan et al, 202068 | ||
| Parameter . | Value . | Reference . | ||
|---|---|---|---|---|
| Weight | Age-dependent Example: 30 years old: 89.30 kg | CDC NHANES22,23 | ||
| Cost-effectiveness threshold | $150 000 per added QALY | Institute for Clinical and Economic Review45 | ||
| Dosage | Supplemental Table 4 | BeneFix package insert46; ALPROLIX package insert47; Lexicomp9; Srivastava et al, 20205 | ||
| Costs Clotting factor (base case) Clotting factor (sensitivity analysis) Hospital bed/night Investigations Total joint replacement surgery (excluding factor concentrate) Gene therapy base case cost Gene therapy manufacturing cost (sensitivity analysis) Gene therapy follow-up cost | • SHL-FIX (BeneFix): $1.41/IU • EHL-FIX (ALPROLIX)*: $3.24/IU • SHL-FIX: $0.3/IU • EHL-FIX: $0.65/IU $995 Supplemental Tables 5 and 6 $13 187 $2 000 000 Total: $77 289 Direct costs: $48 917, indirect costs (58% of direct costs): $28 372 (Table 2) $9909 | WAC obtained from Redbook Online from Micromedex Solutions Knight et al, 200310; Farrugia et al, 201333; Miners, 200932; International Medical Products Price Guide (MSH) online database49 WHO-CHOICE Tool26 Centers for Medicare & Medicaid Services Online Database27 Medicare Procedure Price Lookup Online Database50; Centers for Medicare & Medicaid Services Online Database27 Cook et al, 202025; Wall Street Journal, 202024 Direct estimate of manufacturing cost from Children’s GMP, LLC, at SJCRH30 Centers for Medicare & Medicaid Services Online Database27 | ||
| Utilities On-demand Prophylaxis Gene therapy Joint damage decrement Minor bleed decrement Major bleed decrement Total joint replacement surgery decrement Injection decrement | 0.6705 – (0.0019 × age) 0.9378 – (0.0026 × age) Assumed to be the same as United States general population utilities (supplemental Figure 1) Depends on the year of joint damage; ranges between −0.14 and −0.38 (supplemental Table 4) −0.06 (for 1 wk) −0.18 (for 1 wk) −0.14 (for 1 mo) −0.0004 | Noone et al, 201351, Farrugia et al, 201333, Ara and Brazier, 201052 Szende et al, 201453 Carroll et al, 201954 Hoxer et al, 201955 Cook et al, 202025 | ||
| Transition probabilities/rates | ||||
| Annual bleeding rate (minor and major) Hospitalization Joint damage and total joint replacement surgery Mortality | Minor bleeds: • Prophylaxis: 1.2-5.5 • On-demand: 9.0-35.1 Major bleeds: • Prophylaxis: 0-0.2 • On-demand: 0.1-0.62 Post–gene therapy: No bleeding for 9 y, then minor bleeds occurred as the factor level dropped. Eventually, patient moved back to prophylaxis when the factor level dropped below 3 IU/dL (supplemental Table 4) Major bleed: hospitalization for 5 d per episode • Prophylaxis: None • On-demand/inhibitor: 1-3 per lifetime Supplemental Table 4 | Chen et al, 201756; Windyga et al, 201457; Collins et al, 201858; Kavakli et al, 201659; Powell et al, 201360; Lambert et al, 200761; Valentino et al, 201462; Santagostino et al, 201663; Shih et al, 201964; Ludlam et al, 200065; Soucie et al, 201816 BeneFix package insert46; ALPROLIX package insert47; Lexicomp9; Colowick et al, 200011; Knight et al, 200310 Castaman 201841; Lin et al, 201866 CDC WONDER,67 Hassan et al, 202068 | ||
CDC, Centers for Disease Control and Prevention; NHANES, National Health and Nutrition Examination Survey.
Several FIX-EHL products were analyzed. ALPROLIX was selected for inclusion in the model over IDELVION because based on the cost per unit and the package insert dosing instructions, it was the more cost-effective option. Comparative analysis of ALPROLIX vs IDELVION is available in supplemental Tables 9 and 10.