Base-case input parameters and probability distributions
| Input parameter . | Value . | Probability distribution used in probabilistic sensitivity analysis . | Data source . |
|---|---|---|---|
| Cohort age at start | 63 | Fixed | InHIBIT-Bleed9 |
| Discount rate | 0.03 | Fixed | Sanders et al17 |
| Patient weight, mean, kg | 84.05 | Fixed | CDC24 |
| Mean US hourly wage, USD | 34.10 | Fixed | US Bureau of Labor Statistics25 |
| Hazard ratio of mortality, HHT : non-HHT individuals | 2.0 | Fixed | Donaldson et al5 |
| Median number of RBC units transfused, 6 mo before treatment | 9 | γ (0.9138, 0.06741) | InHIBIT-Bleed9 |
| Median number of RBC units transfused, first 6 mo on Bev | 0 | γ (0.3832, 0.1571) | InHIBIT-Bleed9 |
| Median number of iron units infused, 6 mo before treatment | 8 | γ (1.680, 0.1472) | InHIBIT-Bleed9 |
| Median number of iron units infused, first 6 mo on Bev | 2 | γ (0.6645, 0.2086) | InHIBIT-Bleed9 |
| Mean number of ED visits or admissions, 6 mo before treatment | 0.96 | β-PERT (0.48, 1.44) | InHIBIT-Bleed9 |
| Mean number of ED visits or admissions, first 6 mo on Bev | 0.30752 | β-PERT (0.1538, 0.4613) | InHIBIT-Bleed9 |
| Mean number of endoscopic hemostatic procedures, 6 mo before treatment | 0.60123 | β-PERT (0.3006, 0.9018) | InHIBIT-Bleed9 |
| Mean number of endoscopic hemostatic procedures, first 6 mo on Bev | 0.06641 | β-PERT (0.0332, 0.0996) | InHIBIT-Bleed9 |
| Mean number of ENT hemostatic procedures, 6 mo before treatment | 0.47573 | β-PERT (0.0996, 0.7135) | InHIBIT-Bleed9 |
| Mean number of ENT hemostatic procedures, first 6 mo on Bev | 0.14740 | β-PERT (0.073698002, 0.221094006) | InHIBIT-Bleed9 |
| Transition probabilities | |||
| Probability of major AE leading to Bev discontinuation, first year of treatment | 0.02363 | β-PERT (0.0118, 0.0354) | InHIBIT-Bleed9 |
| Assumed of major AE leading to Bev discontinuation, all subsequent years | 0.00239 | β-PERT (0.001194, 0.003582) | Assumed - 10% of first year probability |
| Probability of delayed hemolytic transfusion reaction | 4.55E-05 | β-PERT (2.27E-05, 6.82E-05) | Goel et al13 |
| Probability of transfusion aasociated circulatory overload | 0.000111 | β-PERT (5.56E-05, 1.67E-04) | Goel et al13 |
| Probability of transfusion-related acute lung injury | 1.67E-05 | β-PERT (8.33E-06, 2.50E-05) | Goel et al13 |
| Probability of PTP | 7.69E-08 | β-PERT (3.85E-08, 1.15E-07) | Goel et al13 |
| Probability of ferric carboxymaltose anaphylaxis | 3.31E-05 | β-PERT (1.66E-05, 4.97E-05) | Durup et al14 |
| Probability of ferumoxytol anaphylaxis | 3.41E-04 | β-PERT (1.71E-04, 5.12E-04) | Wang et al15 |
| Probability of iron dextran anaphylaxis | 7.90E-06 | β-PERT (3.95E-06, 1.19E-05) | Durup et al14 |
| Probablity of death from DHTR | 0.038 | β-PERT (0.019, 0.057) | Davies et al26 |
| Probability of death from TACO | 0.084 | β-PERT (0.042, 0.13) | 2021 SHOT Report12 |
| Probability of death from TRALI | 0.075 | β-PERT (0.0375, 0.1125) | Popovsky27 |
| Probability of death from PTP | 0.046 | β-PERT (0.023, 0.069) | Davies et al26 |
| Probability of death due to Ferric carboxymaltose anaphylaxis | 0.002 | β-PERT (0.001, 0.003) | Trumbo et al16 |
| Probability of death due to ferumoxytol anaphylaxis | 0.13 | β-PERT (0.067, 0.20) | Trumbo et al16 |
| Probability of death due to iron dextran anaphylaxis | 0.045 | β-PERT (0.022, 0.068) | Trumbo et al16 |
| Utility values | |||
| Utility of HHT disease state | Age-dependent | β-PERT | Zarrabeitia et al6 |
| Utility increment of anemia improvement (severe to moderate) | 0.05 | β-PERT (0.045, 0.055) | GBD 201928 |
| Estimated disutility of major AE due to Bev | –0.00261 | β-PERT (–0.00288, –0.00235) | Assumed |
| Disutility of transfusion-related acute lung injury | –0.01538 | β-PERT (–0.01692, –0.0547) | van Eerd et al29 |
| Disutility of delayed hemolytic transfusion reaction | –0.00608 | β-PERT (–0.00668, –0.00547) | Lloyd et al30 |
| Disutility of transfusion-associated circulatory overload | –0.01538 | β-PERT (–0.01692, –0.0547) | van Eerd et al29 |
| Disutility of PTP | –0.00885 | β-PERT (–0.00973, –0.00796) | Di Minno et al31 |
| Disutility of iron anaphylaxis | –0.000740 | β-PERT (–0.000814, –0.000665) | Shaker et al32 |
| Costs (USD) | |||
| Cost of bevacizumab per mg | 7.0752 | Fixed | HCPCS 4436311 |
| Cost per unit of RBC | 135.52 | Fixed | HCPCS P902111 |
| Cost of ferric carboxymaltose per infusion | 826.5 | Fixed | HCPCS J143911 |
| Cost of ferumoxytol per infusion | 283.56 | Fixed | HCPCS Q013811 |
| Cost of iron dextran per infusion | 33.16 | Fixed | HCPCS J175011 |
| Cost of ED visit | 381.61 | γ (16, 0.04192) | HCPCS 9928411 |
| Cost of hospital admission | 37266.09 | γ (16, 0.0004293) | Harder et al33 |
| Cost of endoscopic hemostatic procedure | 1412.25 | γ (16, 0.01133) | HCPCS 4439111 |
| Cost of ENT hemostatic procedure | 8501.26 | γ (16, 0.001882) | Rudmik et al, Healthcare Bluebook34,35 |
| Cost of delayed hemolytic transfusion reaction treatment | 1537 | γ (16, 0.01041) | Janssen et al36 |
| Cost of transfusion-associated circulatory overload treatment | 4830 | γ (16, 0.003313) | Janssen et al36 |
| Cost of transfusion-related acute lung injury | 9959 | γ (16, 0.001607) | Janssen et al36 |
| Cost of PTP treatment | 2536.58 | γ (16, 0.006308) | Davies et al26 |
| Cost of ferric carboxymaltose anaphylaxis treatment | 2124.61 | γ (16, 0.007531) | Trumbo et al16 |
| Cost of ferumoxytol anaphylaxis treatment | 9491.83 | γ (16, 0.001686) | Trumbo et al16 |
| Cost of iron dextran anaphylaxis treatment | 10016.19 | γ (16, 0.001597) | Trumbo et al16 |
| Input parameter . | Value . | Probability distribution used in probabilistic sensitivity analysis . | Data source . |
|---|---|---|---|
| Cohort age at start | 63 | Fixed | InHIBIT-Bleed9 |
| Discount rate | 0.03 | Fixed | Sanders et al17 |
| Patient weight, mean, kg | 84.05 | Fixed | CDC24 |
| Mean US hourly wage, USD | 34.10 | Fixed | US Bureau of Labor Statistics25 |
| Hazard ratio of mortality, HHT : non-HHT individuals | 2.0 | Fixed | Donaldson et al5 |
| Median number of RBC units transfused, 6 mo before treatment | 9 | γ (0.9138, 0.06741) | InHIBIT-Bleed9 |
| Median number of RBC units transfused, first 6 mo on Bev | 0 | γ (0.3832, 0.1571) | InHIBIT-Bleed9 |
| Median number of iron units infused, 6 mo before treatment | 8 | γ (1.680, 0.1472) | InHIBIT-Bleed9 |
| Median number of iron units infused, first 6 mo on Bev | 2 | γ (0.6645, 0.2086) | InHIBIT-Bleed9 |
| Mean number of ED visits or admissions, 6 mo before treatment | 0.96 | β-PERT (0.48, 1.44) | InHIBIT-Bleed9 |
| Mean number of ED visits or admissions, first 6 mo on Bev | 0.30752 | β-PERT (0.1538, 0.4613) | InHIBIT-Bleed9 |
| Mean number of endoscopic hemostatic procedures, 6 mo before treatment | 0.60123 | β-PERT (0.3006, 0.9018) | InHIBIT-Bleed9 |
| Mean number of endoscopic hemostatic procedures, first 6 mo on Bev | 0.06641 | β-PERT (0.0332, 0.0996) | InHIBIT-Bleed9 |
| Mean number of ENT hemostatic procedures, 6 mo before treatment | 0.47573 | β-PERT (0.0996, 0.7135) | InHIBIT-Bleed9 |
| Mean number of ENT hemostatic procedures, first 6 mo on Bev | 0.14740 | β-PERT (0.073698002, 0.221094006) | InHIBIT-Bleed9 |
| Transition probabilities | |||
| Probability of major AE leading to Bev discontinuation, first year of treatment | 0.02363 | β-PERT (0.0118, 0.0354) | InHIBIT-Bleed9 |
| Assumed of major AE leading to Bev discontinuation, all subsequent years | 0.00239 | β-PERT (0.001194, 0.003582) | Assumed - 10% of first year probability |
| Probability of delayed hemolytic transfusion reaction | 4.55E-05 | β-PERT (2.27E-05, 6.82E-05) | Goel et al13 |
| Probability of transfusion aasociated circulatory overload | 0.000111 | β-PERT (5.56E-05, 1.67E-04) | Goel et al13 |
| Probability of transfusion-related acute lung injury | 1.67E-05 | β-PERT (8.33E-06, 2.50E-05) | Goel et al13 |
| Probability of PTP | 7.69E-08 | β-PERT (3.85E-08, 1.15E-07) | Goel et al13 |
| Probability of ferric carboxymaltose anaphylaxis | 3.31E-05 | β-PERT (1.66E-05, 4.97E-05) | Durup et al14 |
| Probability of ferumoxytol anaphylaxis | 3.41E-04 | β-PERT (1.71E-04, 5.12E-04) | Wang et al15 |
| Probability of iron dextran anaphylaxis | 7.90E-06 | β-PERT (3.95E-06, 1.19E-05) | Durup et al14 |
| Probablity of death from DHTR | 0.038 | β-PERT (0.019, 0.057) | Davies et al26 |
| Probability of death from TACO | 0.084 | β-PERT (0.042, 0.13) | 2021 SHOT Report12 |
| Probability of death from TRALI | 0.075 | β-PERT (0.0375, 0.1125) | Popovsky27 |
| Probability of death from PTP | 0.046 | β-PERT (0.023, 0.069) | Davies et al26 |
| Probability of death due to Ferric carboxymaltose anaphylaxis | 0.002 | β-PERT (0.001, 0.003) | Trumbo et al16 |
| Probability of death due to ferumoxytol anaphylaxis | 0.13 | β-PERT (0.067, 0.20) | Trumbo et al16 |
| Probability of death due to iron dextran anaphylaxis | 0.045 | β-PERT (0.022, 0.068) | Trumbo et al16 |
| Utility values | |||
| Utility of HHT disease state | Age-dependent | β-PERT | Zarrabeitia et al6 |
| Utility increment of anemia improvement (severe to moderate) | 0.05 | β-PERT (0.045, 0.055) | GBD 201928 |
| Estimated disutility of major AE due to Bev | –0.00261 | β-PERT (–0.00288, –0.00235) | Assumed |
| Disutility of transfusion-related acute lung injury | –0.01538 | β-PERT (–0.01692, –0.0547) | van Eerd et al29 |
| Disutility of delayed hemolytic transfusion reaction | –0.00608 | β-PERT (–0.00668, –0.00547) | Lloyd et al30 |
| Disutility of transfusion-associated circulatory overload | –0.01538 | β-PERT (–0.01692, –0.0547) | van Eerd et al29 |
| Disutility of PTP | –0.00885 | β-PERT (–0.00973, –0.00796) | Di Minno et al31 |
| Disutility of iron anaphylaxis | –0.000740 | β-PERT (–0.000814, –0.000665) | Shaker et al32 |
| Costs (USD) | |||
| Cost of bevacizumab per mg | 7.0752 | Fixed | HCPCS 4436311 |
| Cost per unit of RBC | 135.52 | Fixed | HCPCS P902111 |
| Cost of ferric carboxymaltose per infusion | 826.5 | Fixed | HCPCS J143911 |
| Cost of ferumoxytol per infusion | 283.56 | Fixed | HCPCS Q013811 |
| Cost of iron dextran per infusion | 33.16 | Fixed | HCPCS J175011 |
| Cost of ED visit | 381.61 | γ (16, 0.04192) | HCPCS 9928411 |
| Cost of hospital admission | 37266.09 | γ (16, 0.0004293) | Harder et al33 |
| Cost of endoscopic hemostatic procedure | 1412.25 | γ (16, 0.01133) | HCPCS 4439111 |
| Cost of ENT hemostatic procedure | 8501.26 | γ (16, 0.001882) | Rudmik et al, Healthcare Bluebook34,35 |
| Cost of delayed hemolytic transfusion reaction treatment | 1537 | γ (16, 0.01041) | Janssen et al36 |
| Cost of transfusion-associated circulatory overload treatment | 4830 | γ (16, 0.003313) | Janssen et al36 |
| Cost of transfusion-related acute lung injury | 9959 | γ (16, 0.001607) | Janssen et al36 |
| Cost of PTP treatment | 2536.58 | γ (16, 0.006308) | Davies et al26 |
| Cost of ferric carboxymaltose anaphylaxis treatment | 2124.61 | γ (16, 0.007531) | Trumbo et al16 |
| Cost of ferumoxytol anaphylaxis treatment | 9491.83 | γ (16, 0.001686) | Trumbo et al16 |
| Cost of iron dextran anaphylaxis treatment | 10016.19 | γ (16, 0.001597) | Trumbo et al16 |
AE, adverse event; Bev, bevacizumab; ED, emergency department; DHTR, delayed hemolytic transfusion reactions; ENT, ear-nose-throat; PERT, program evaluation and review technique; PTP, posttransfusion purpura; TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung injury; USD, US dollars.