Background
Methods
Model structure
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○ No symptoms (no left ventricular hypertrophy, kidney disease, white matter lesions or complications)
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○ Acroparesthesia (neuropathic pain in the extremities)
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○ Symptoms (more accurately: clinical signs and/or symptoms of left ventricular hypertrophy, chronic kidney disease stages 1-4, or white matter lesions)
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○ End stage renal disease (chronic kidney disease stage 5, dialysis or kidney transplant)
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○ Cardiac complication(s) (atrial fibrillation, any other rhythm disturbance needing hospitalization, pacemaker or implantable cardiac defibrillator (ICD) implantation, cardiac congestion for which hospital admittance was needed, myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft)
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○ Cerebrovascular accident (stroke, as diagnosed by a neurologist)
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○ End stage renal disease and cardiac complication(s)
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○ End stage renal disease and cerebrovascular accident
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○ Cardiac complication(s) and cerebrovascular accident
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○ End stage renal disease and cardiac complication(s) and cerebrovascular accident
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○ Death
Model data sources and assumptions
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state-transition probabilities for the natural (untreated) course of Fabry disease are based on the period prior to the introduction of ERT therapy;
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ERT only decreases the probability of progressing to the next disease state;
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health utilities, health care volumes and related costs for treated as well as untreated males and females are similar for patients in the same disease state;
Transition probabilities
Health outcomes
N* | Mean health utility | 95% LCL | 95% UCL | |
---|---|---|---|---|
Asymptomatic | 19 | 0.874 | 0.804 | 0.934 |
Acroparesthesia/Symptomatic | 55 | 0.762 | 0.699 | 0.822 |
Single complication | 18 | 0.744 | 0.658 | 0.821 |
Multiple complications | 5 | 0.584 | 0.378 | 0.790 |
Total | 97 | 0.772 | 0.729 | 0.815 |
Health care volume and costs
Resource | Unit costs in 2009 (€)# | Source |
---|---|---|
Inpatient hospital day | ||
AMC | 596-1,036 | AMC hospital ledger## |
Elsewhere* | 457 | Dutch costing manual** |
Inpatient hospital ICU day | 2,183 | Dutch costing manual |
In-hospital day-care treatment | ||
AMC | 274 - 845 | AMC hospital ledger |
Elsewhere | 251 | Dutch costing manual |
Agalsidase α/β*** per patient per year | 200,000 | Report manufacturer 2010; z-index 2007 |
Kidney dialysis per year | 60,000 | |
Kidney transplantation | ||
first year | 60,000 | |
follow-up per year | not included | |
Other diagnostic and therapeutic procedures | Various | AMC hospital ledger |
Outpatient hospital visit | ||
AMC | 90 - 460 | AMC hospital ledger |
Elsewhere* | 72 | Dutch costing manual |
Out-of-hospital visit | ||
General practitioner | 28 | Dutch costing manual |
Physiotherapist | 36 | Dutch costing manual |
Psychiatrist/psychologist† | 91.5 | Dutch costing manual |
Occupational physician/other†† | 26 | AMC hospital ledger |
Social worker | 65 | Dutch costing manual |
Alternative healer | 60 | Expert opinion††† |
Productivity loss per hour^ | 30 | Dutch costing manual |
Analysis
Results
Base case scenario
Discount rate 1.5% | Discount rate 0% | |||||
---|---|---|---|---|---|---|
ERT | No ERT | Difference | ERT | No ERT | Difference | |
ALL
| ||||||
YFEOD | 36.9 | 36.1 | 0.7 | 56.5 | 55.0 | 1.5 |
QALYs | 32.1 | 31.3 | 0.7 | 50.2 | 48.6 | 1.6 |
MALES
| ||||||
YFEOD | 36.2 | 35.4 | 0.8 | 55.1 | 53.5 | 1.6 |
QALYs | 31.7 | 30.9 | 0.8 | 49.5 | 47.8 | 1.7 |
FEMALES
| ||||||
YFEOD | 37.7 | 37.1 | 0.6 | 58.2 | 56.9 | 1.3 |
QALYs | 32.6 | 31.9 | 0.7 | 51.1 | 49.7 | 1.4 |
Discount rate 4% | Discount rate 0% | |||||
---|---|---|---|---|---|---|
ERT | No ERT | Difference | ERT | No ERT | Difference | |
ALL | €2,504,727 | €83,772 | €2,420,956 | €9,918.352 | €270,964 | €9.647,388 |
MALES | €2,433,824 | €85,305 | €2,348,519 | €9,615,920 | €272,892 | €9,343,028 |
FEMALES | €2,516,273 | €81,624 | €2,434,649 | €10,056,623 | €267,517 | €9,789,106 |
Discount rate at 1.5% for effects and 4% for costs | Discount rate at 0% for effects and costs | |
---|---|---|
ALL | ||
Incremental costs per extra year free of end-organ damage | €3,318,239 | €6,560,885 |
Incremental costs per QALY gained | €3,282,252 | €6,065,529 |
MALES | ||
Incremental costs per extra year free of end-organ damage | €2,982,022 | €5,917,091 |
Incremental costs per QALY gained | €2,947,380 | €5,451,797 |
FEMALES | ||
Incremental costs per extra year free of end-organ damage | €3,797,767 | €7,527,013 |
Incremental costs per QALY gained | €3,742,702 | €6,955,612 |
Scenario analyses
ICER based on years free of end-organ damage, in € | ICER based QALYs, in € | |||
---|---|---|---|---|
Discounted | Undiscounted | Discounted | Undiscounted | |
Base case typical patient | 3,318,239 | 6,560,885 | 3,282,252 | 6,065,529 |
1. start ERT at 40 years | 3,662,891 | 12,996,662 | 2,158,245 | 7,637,076 |
2. lower QoL during the natural course | - | - | 509,719 | 1,226,674 |
3. course of disease in patients with the classical phenotype only | 3,274,869 | 6,280,356 | 3,015,385 | 5,575,064 |
4. ACE-ARB during natural course | 293,213,929 | 566,675,324 | 11,559,105 | 21,223,686 |
5. No ERT in case of 2 complications | 3,307,363 | 6,529,644 | 3,271,494 | 6,036,644 |
6. including indirect costs of production loss | 3,320,374 | 6,568,971 | 3,284,265 | 6,073,006 |