Key points
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This comprehensive study measured the direct and indirect costs of individuals with TSC and their caregivers
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Mean total direct costs (healthcare and non-healthcare) were estimated at EUR 6452 over three months
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Medication, particularly mTOR inhibitors, were major direct cost components, followed by hospitalization and outpatient treatment
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Mean total indirect costs were estimated at EUR 3174 over three months; with an inability to work being the largest factor
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Total cost is driven by the number of TSC manifestations and affected organ systems
Background
Methods
Patients and recruitment
Survey methods
Costing methods
Direct health care costs
Out-of-pocket expenses
Care grade allowances as approximation of informal care costs
Indirect costs
Grouping of questionnaire items
Statistical analysis
Results
Demographic and clinical characteristics
All patients n = 192 | |
---|---|
Age in years1 | 33.4 ± 12.7 |
Range | |
18.0–78.0 | |
Sex | % (n) |
Male | 48.4 (93) |
Female | 51.6 (99) |
Age at first symptoms due to TSC1 | 5.7 ± 12.0 |
Range | |
0.0–66.0 | |
Age at TSC diagnosis in years1 | 10.4 ± 14.9 |
Range | |
0.0–66.0 | |
TSC diagnosis before birth by ultrasound | % (n) |
No | 96.9 (186) |
Yes | 1.6 (3) |
Genetics | % (n) |
TSC1-gene | 16.7 (32) |
TSC2-gene | 25.0 (48) |
TSC2/PKD1 contiguous-gene | 1.6 (3) |
No genetic test | 30.7 (59) |
No genetic mutation | 10.4 (20) |
Unknown | 15.6 (30) |
Affected family members by TSC | % (n) |
No | 77.6 (149) |
Yes | 18.8 (36) |
Mother affected (43.9 years)2 | 4.7 (9) |
Father affected (46.3 years)2 | 3.6 (7) |
Sibling affected (4.8 years)2 | 6.8 (13) |
Own children affected (3.0 years)2 | 8.9 (17) |
Number of own affected children | Mean |
1.4 | |
Marital status | % (n) |
Married/living in relationship | 22.9 (44) |
Divorced | 1.6 (3) |
Single, lives with relatives | 43.8 (84) |
Single, lives alone | 29.7 (57) |
Unknown/Other | 2.1 (4) |
School education | % (n) |
< 12 years | 42.7 (82) |
> 12 years | 20.8 (40) |
Still going to school | 4.7 (9) |
No school graduation | 30.2 (58) |
Not answered | 1.6 (3) |
Highest job qualification | % (n) |
Missing | 42.2 (81) |
Skilled (manual) | 23.4 (45) |
Office-based (nonmanual) | 5.7 (11) |
University degree | 9.9 (19) |
In training | 8.3 (16) |
Unknown/Other | 10.4 (20) |
Employment situation | % (n) |
Employed | 37.0 (71) |
Vocational training | 10.9 (21) |
Unemployed | 21.4 (41) |
Homemaker/parental leave | 1.0 (2) |
Early retirement | 9.9 (19) |
Old-age pension | 1.0 (2) |
Unknown/Other | 18.8 (36) |
% | n | |
---|---|---|
Epilepsy | 72.9 | 140 |
Recurrent seizures | 39.1 | 75 |
Seizure free > 1 year or no seizures | 60.9 | 117 |
Structural brain disorders | 67.2 | 129 |
Cortical tubers | 49.0 | 94 |
SEGA1 | 37.5 | 72 |
Hydrocephalus | 2.6 | 5 |
Psychiatric disorders | 50.5 | 97 |
Heart and circulatory system | 50.5 | 97 |
Hypertension | 26.6 | 51 |
Rhabdomyomas | 24.5 | 47 |
Arrhythmia | 8.3 | 16 |
Kidney and urinary tract | 74.0 | 142 |
Angiomyolipomas | 59.4 | 114 |
Cysts | 42.2 | 81 |
Chronic kidney dysfunction | 12.5 | 24 |
Renal cell carcinoma | 2.6 | 5 |
Skin manifestations | 94.8 | 182 |
Angiofibromas | 84.9 | 163 |
Hypomelanotic macules | 57.3 | 110 |
Shagreen patches | 48.4 | 93 |
Ungal/periungal fibromas | 10.9 | 21 |
Skin tags | 3.6 | 7 |
Café au lait spots | 2.6 | 5 |
Lymphangioleiomyomatosis | 11.5 | 22 |
Other disorders | 39.1 | 75 |
Iris or retinal hamartomas/astrocytomas and other eye disorders | 28.6 | 55 |
Angiomyolipomas in other organ systems2 | 14.1 | 27 |
Cysts in other organ systems2 | 13.0 | 25 |
Direct costs
Cost components | Mean costs | SD1 | Minimum | Median | Maximum | 95% CI | % of total direct costs | Estimated annual direct costs2 |
---|---|---|---|---|---|---|---|---|
Total direct costs | 6452 | 7584 | 0 | 1920 | 29,182 | 5533; 7422 | 100 | 25,808 |
Medication (n = 165) | 4953 | 6854 | 0 | 573 | 28,224 | 4087; 5876 | 76.8 | 19,812 |
mTOR inhibitors* (n = 71) | 4358 | 6520 | 0 | 0 | 25,273 | 3448; 5342 | 67.5 | 17,432 |
Antiseizure drugs (ASDs) (n = 123) | 415 | 1962 | 0 | 104 | 26,538 | 239; 706 | 6.4 | 1660 |
Other prescription drugs (n = 104) | 132 | 385 | 0 | 8 | 2606 | 84; 186 | 2.0 | 528 |
OTC drugs and supplements (n = 70) | 41 | 100 | 0 | 0 | 700 | 29; 54 | 0.6 | 164 |
Emergency medication/medication on demand (n = 42) | 7 | 36 | 0 | 0 | 347 | 3; 13 | 0.1 | 28 |
Hospitalization (n = 23) | 518 | 1691 | 0 | 0 | 11,487 | 312; 750 | 8.0 | 2072 |
Outpatient treatment (n = 157) | 467 | 1156 | 0 | 194 | 15,097 | 352; 626 | 7.2 | 1868 |
Diagnostics (n = 140) | 155 | 242 | 0 | 44 | 1691 | 124; 192 | 2.4 | 620 |
Ancillary therapies (n = 54) | 125 | 307 | 0 | 0 | 2120 | 84; 174 | 1.9 | 500 |
Auxillary material (n = 14) | 49 | 253 | 0 | 0 | 2235 | 18; 87 | 0.8 | 196 |
Rehabilitation (n = 2) | 40 | 410 | 0 | 0 | 4983 | 0; 92 | 0.6 | 160 |
Emergency service use (n = 9) | 44 | 217 | 0 | 0 | 1800 | 19; 75 | 0.7 | 176 |
Specific diets (n = 3) | 9 | 97 | 0 | 0 | 1200 | 0; 23 | 0.1 | 36 |
Transport costs (n = 25) | 5 | 17 | 0 | 0 | 130 | 3; 7 | 0.1 | 20 |
Co-payments for therapies (n = 17) | 39 | 177 | 0 | 0 | 1400 | 19; 64 | 0.6 | 156 |
Other co-payments (n = 45) | 48 | 183 | 0 | 0 | 1700 | 27; 75 | 0.7 | 192 |
Medication costs | n | Mean costs per 3 months | SD1 | Minimum | Median | Maximum | 95% CI | p-value2 |
---|---|---|---|---|---|---|---|---|
All patients | 192 | € 415 | 1962 | € 0 | € 104 | € 26,538 | 239; 706 | |
No ASDs (35.9%) | 69 | 0 | ||||||
Monotherapy (24.0%) | 46 | € 222 | 400 | € 15 | € 125 | € 2613 | 136; 354 | < 0.0013 |
2 ASDs (26.0%) | 50 | € 327 | 317 | € 50 | € 238 | € 1405 | 250; 415 | < 0.0104 |
≥ 3 ASDs (14.1%) | 27 | € 1965 | 4979 | € 144 | € 962 | € 26,538 | 826, 4016 | < 0.0015 |
Prescribed medication | n | Mean daily dose | SD1 | Minimum | Median | Maximum | Mean costs per 3 months | SD1 |
---|---|---|---|---|---|---|---|---|
Lamotrigine (26.6%) | 51 | 362 mg | 373 mg | 50 mg | 300 mg | 2500 mg | € 90 | 93 |
Valproate (24.0%) | 46 | 1355 mg | 465 mg | 450 mg | 1250 mg | 2300 mg | € 62 | 21 |
Oxcarbazepine (16.7%) | 32 | 1617 mg | 708 mg | 150 mg | 1800 mg | 3600 mg | € 226 | 99 |
Levetiracetam (13.0%) | 25 | 2400 mg | 1090 mg | 750 mg | 2250 mg | 4500 mg | € 161 | 73 |
Lacosamide (6.3%) | 12 | 410 mg | 283 mg | 100 mg | 350 mg | 1200 mg | € 894 | 616 |
Topiramate (3.6%) | 7 | 225 mg | 56 mg | 150 mg | 200 mg | 300 mg | € 149 | 37 |
Zonisamide (3.6%) | 7 | 657 mg | 450 mg | 300 mg | 500 mg | 1600 mg | € 1087 | 745 |
Carbamazepine (3.1%) | 6 | 700 mg | 490 mg | 300 mg | 500 mg | 1600 mg | € 35 | 24 |
Perampanel (3.1%) | 6 | 5 mg | 2 mg | 2 mg | 6 mg | 8 mg | € 308 | 120 |
Brivaracetam (2.6%) | 5 | 220 mg | 76 mg | 150 mg | 200 mg | 350 mg | € 508 | 175 |
Sulthiame (2.6%) | 5 | 530 mg | 470 mg | 100 mg | 450 mg | 1250 mg | € 320 | 284 |
Vigabatrine (2.6%) | 5 | 2200 mg | 758 mg | 1000 mg | 2500 mg | 3000 mg | € 397 | 137 |
Phenytoin (2.1%) | 4 | 331 mg | 85 mg | 250 mg | 313 mg | 450 mg | € 26 | 7 |
Primidone (2.1%) | 4 | 750 mg | 451 mg | 375 mg | 625 mg | 1250 mg | € 38 | 23 |
Phenobarbital (2.1%) | 4 | 141 mg | 106 mg | 10 mg | 163 mg | 230 mg | € 62 | 47 |
Rufinamid (1.6%) | 3 | 1267 mg | 702 mg | 600 mg | 1200 mg | 2000 mg | € 759 | 421 |
Clobazame (1.6%) | 3 | 25 mg | 13 mg | 15 mg | 20 mg | 40 mg | € 68 | 36 |
Gabapentin (1.6%) | 3 | 967 mg | 1250 mg | 100 mg | 400 mg | 2400 mg | € 78 | 101 |
Other ASDs* (5.7%) | 11 |
Care needs and care grade as approximators of informal care costs
Indirect (productivity) costs
Indirect costs components | n1 | Mean costs | SD2 | Minimum | Median | Maximum | 95% CI | Estimated annual costs3 |
---|---|---|---|---|---|---|---|---|
Total indirect costs (< 67 y) | 86 | 3174 | 4703 | 0 | 0 | 11,241 | 2503; 3840 | 12,696 |
Inability to work | 30 | 1775 | 4110 | 0 | 0 | 11,241 | 1183; 2367 | 7100 |
Reduction of working hours | 19 | 514 | 1762 | 0 | 0 | 9695 | 283; 792 | 2056 |
Unemployment | 6 | 355 | 1971 | 0 | 0 | 11,241 | 118; 651 | 1420 |
Early retirement | 5 | 296 | 1804 | 0 | 0 | 11,241 | 59; 592 | 1184 |
Days off | 28 | 234 | 1050 | 0 | 0 | 10,750 | 115; 382 | 936 |
Cost drivers of direct, indirect, and approximated informal (nursing) care costs
n | Total direct costs in € | Median | SD | p-value§ | Total indirect costs in €** | Median | SD | p-value§ | Nursing care level costs in € | Median | SD | p-value§ | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Gender | 0.321 | 0.088 | 0.082 | ||||||||||
Male | 93 | 6173 | 1527 | 8156 | 2796 | 0 | 4687 | 1079 | 948 | 1102 | |||
Female | 99 | 6714 | 2722 | 7036 | 3529 | 538 | 4714 | 788 | 0 | 1016 | |||
Age | 0.012* | 0.062*# | 0.003* | ||||||||||
18–29 years | 90 | 8067 | 3460 | 8419 | 2171 | 0 | 4117 | 1084 | 948 | 1081 | |||
30–39 years | 54 | 5849 | 1646 | 6700 | 3978 | 323 | 5081 | 1072 | 948 | 1072 | |||
40 years and above | 48 | 4102 | 1350 | 6154 | 4192 | 430 | 5011 | 477 | 0 | 911 | |||
Number of antiseizure drugs | < 0.001 | 0.057 | < 0.001 | ||||||||||
≥ 2 | 77 | 9237 | 9743 | 8639 | 4054 | 430 | 5131 | 1461 | 1635 | 1004 | |||
0—1 | 115 | 4587 | 1224 | 6155 | 2574 | 0 | 4308 | 573 | 0 | 955 | |||
mTOR inhibitors intake | < 0.001# | 0.510 | 0.250 | ||||||||||
Yes | 71 | 14,473 | 13,100 | 5641 | 3335 | 0 | 4729 | 1041 | 948 | 1085 | |||
No | 121 | 1746 | 712 | 3548 | 3077 | 0 | 4705 | 863 | 0 | 1053 | |||
Seizures | < 0.001# | 0.105 | < 0.001 | ||||||||||
Recurrent seizures | 75 | 9082 | 5440 | 8930 | 3859 | 323 | 5061 | 1530 | 1635 | 1055 | |||
Seizure free > 1 year or no seizures | 117 | 4729 | 1401 | 5997 | 2717 | 0 | 4412 | 535 | 0 | 875 | |||
Epilepsy | 0.001 | 0.904 | < 0.001# | ||||||||||
Yes (72.9%) | 140 | 7195 | 2184 | 8106 | 3284 | 0 | 4866 | 1249 | 1635 | 1072 | |||
No (27.1%) | 52 | 4451 | 1257 | 5545 | 2866 | 0 | 4242 | 68 | 0 | 288 | |||
Structural brain disorders | 0.003 | 0.889 | 0.014 | ||||||||||
Yes (67.2%) | 129 | 7353 | 2343 | 8041 | 3106 | 0 | 4681 | 1059 | 948 | 1099 | |||
No (32.8%) | 63 | 4607 | 1307 | 6211 | 3318 | 0 | 4784 | 663 | 0 | 947 | |||
Psychiatric disorders | < 0.001 | 0.260 | < 0.001# | ||||||||||
Yes (50.5%) | 97 | 8034 | 2982 | 8083 | 3741 | 0 | 5110 | 1521 | 1635 | 1037 | |||
No (49.5%) | 95 | 4837 | 1199 | 6703 | 2583 | 0 | 4182 | 325 | 0 | 693 | |||
Heart and circulatory manifestations | < 0.001 | 0.558 | 0.170 | ||||||||||
Yes (50.5%) | 97 | 8180 | 6568 | 7764 | 3229 | 0 | 4719 | 1032 | 948 | 1113 | |||
No (49.5%) | 95 | 4687 | 1307 | 7007 | 3118 | 0 | 4710 | 823 | 0 | 1010 | |||
Kidney and urinary tract manifestations | < 0.001 | 0.248 | 0.317 | ||||||||||
Yes (74.0%) | 142 | 7311 | 3357 | 7419 | 3381 | 0 | 4768 | 973 | 474 | 1078 | |||
No (26.0%) | 50 | 4013 | 614 | 7591 | 2594 | 0 | 4511 | 805 | 0 | 1030 | |||
Skin manifestations | 0.009 | 0.296 | 0.004 | ||||||||||
Yes (94.8%) | 182 | 6704 | 2112 | 7669 | 3207 | 0 | 4702 | 980 | 948 | 1072 | |||
No (5.2%) | 10 | 1873 | 380 | 3666 | 2498 | 0 | 4957 | 0 | 0 | 0 | |||
Lung manifestation | 0.030 | 0.014 | 0.139 | ||||||||||
Yes (11.5%) | 22 | 8894 | 7646 | 7928 | 5249 | 2588 | 5220 | 598 | 0 | 912 | |||
No (88.5%) | 170 | 6136 | 1667 | 7505 | 2902 | 0 | 4578 | 972 | 0 | 1079 | |||
Other disorders | 0.013 | 0.116 | 0.959 | ||||||||||
Yes (39.1%) | 75 | 7856 | 7315 | 7352 | 3711 | 430 | 4982 | 938 | 0 | 1070 | |||
No (60.9%) | 117 | 5552 | 1460 | 7625 | 2823 | 0 | 4499 | 923 | 0 | 1067 | |||
Total Disorders | < 0.001* | 0.031* | < 0.001* | ||||||||||
1–3 Manifestations (27.1%) | 52 | 2652 | 331 | 5369 | 1982 | 0 | 3890 | 361 | 0 | 786 | |||
4 Manifestations (20.3%) | 39 | 6488 | 1980 | 7796 | 2676 | 0 | 4299 | 652 | 0 | 922 | |||
5 Manifestations (19.8%) | 38 | 6353 | 1739 | 7158 | 4816 | 1075 | 5345 | 1212 | 1292 | 1065 | |||
6 Manifestations (19.8%) | 38 | 8080 | 6861 | 8022 | 3169 | 215 | 4770 | 1193 | 948 | 1070 | |||
7–8 Manifestations (13.0%) | 25 | 11,977 | 15,151 | 7402 | 3844 | 0 | 5176 | 1709 | 2184 | 1083 | |||
Level of disability | < 0.001 | 0.001# | < 0.001# | ||||||||||
None or ≤ 60% | 68 | 4395 | 496 | 6823 | 1483 | 0 | 3085 | 110 | 0 | 470 | |||
70–100% | 124 | 7580 | 2641 | 7768 | 4074 | 323 | 5158 | 1378 | 1635 | 1034 |
Discussion
Direct costs and related cost drivers
Indirect costs and related cost drivers
Comparison with earlier studies
Zöllner et al. current study | Betts et al. [44] | Chu et al. [45] | Skalicky et al. [43] | Song et al. [37] | Shepherd et al.[16]* | Kingswood et al. [15]* | Kingswood et al. [41]* | Wilson et al. [42] | Sun et al. [38] | Vekeman et al. [40] | Kristof et al. [11] | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Study design | Multicenter, p | Multicenter, r | Multicenter, r | Multicenter, p | Multicenter, r | Multicenter, r | Multicenter, r | Multicenter, r | Multicenter, r | Multicenter, r | Monocenter, r | Multicenter, r |
Costing year | 2019 | 2019 | 2017 | 2012 | 2013 | 2014 | 2014 | 2014 | n.r | 2010 | 2012 | 2011 |
Country (city) | Germany | US | Hong Kong | US | US | UK | UK | UK | US | US | Netherlands(Utrecht) | Canada(Quebec) |
Group | All TSC | TSC and epilepsy | All TSC | All TSC | TSC and AML | TSC and epilepsy | All TSC | TSC and kidneys | All TSC | TSC and SEGA surgery | TSC and kidneys | All TSC (especially LAM) |
Number of patients | 192 | 2028 | 284 | 430 | 487 | 209 | 286 | 79 | 5655 | 47 | 369 | 1004 |
Study population | A | C & A | C & A | A | A | C & A | C & A | C & A | C & A | C & A | C & A | A |
Patients with epilepsy | 72.9% | 100% | 71.3% | n.r | n.r | 100% | n.r | n. r | 41.2% | 91% | n.r | 7.8%# |
Age in years (median) | 18.0–78.0 (31.0) | Mean 25.3 | 0.45–89.9 (27.2) | 19.0–83.0 (36.5) | Mean 36.9 | Mean 26.8 | Mean 31.5 | Mean 38.3 | Mean 22.3 | Mean 11.6 | Mean 42.8 7 | Mean 39.5 |
Patients with AED intake | 64.1% | 89.5% | n. r | n.r | n.r | 88% | 42.7% | 68.4% | n.r | n.r | n.r | 18.3% |
Patients with mTOR-inhibitor intake | 37.0% | 10% | 16.5% | n.r | 8% | n.r | n.r | n.r | n.r | n.r | n.r | 13.4% 3 |
Mean PPPY | Mean PPPY | Mean PPPY | Median PPPY | Mean PPPY | Mean PPPY | Mean PPPY | Mean PPPY | Median | Mean PPPY | Mean PPPY | Mean PPPY | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Total direct costs | EUR 6452 | n.r | n.r | n.r | USD 32,858–48,499 4 | GBP 4778 5 | GBP 4227 5 | GBP 5054 5 | n.r | USD 8543–85,397 6 | EUR 1275–31,916 8 | n.r |
Medication | EUR 4953 | USD 18,836 | n.r | USD 7200 1, 3 | USD 3103–4770 4 | no specific amount | GBP 595 5 (only primary care) | GBP 869 5 (only primary care) | n.r | USD 1300–2338 6 | EUR 429–1508 8 | n.r |
AED | EUR 415 | USD 12,866 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
mTOR inhibitors | EUR 4358 | USD 4028 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Hospitalization | EUR 518 | USD 2106 | USD 5819 1 | USD 2650 2, 3 | USD 15,390–11,787 4 | no specific amount | GBP 2181 5 | GBP 2350 5 | USD 14,807 | USD 3770–71,562 6 | n.r | n.r |
Ancillary therapies | EUR 125 | n.r | n.r | USD 8160 2, 3 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Outpatient treatment | EUR 467 | USD 13,455 | USD 1414 1 | USD 500 2 | USD 13,639–31,158 4 | no specific amount | GBP 645 5 | GBP 690 5 | n.r | USD 3473–11,497 6 | n.r | CAD 513 |
ER visists | n.r | USD 1535 | USD 116 1 | USD 500 2 | USD 725–785 4 | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Mean PPPY | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Total indirect costs | EUR 3174 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Inability to work | EUR 1775 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Part time work | EUR 514 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Unemployment | EUR 355 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Early retirement | EUR 296 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |
Days off | EUR 234 | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r | n.r |