Cost analysis of the treatments for patients with advanced Parkinson's disease: SCOPE study

Figures & data

Table 1.  Healthcare resources identified for every phase and for each therapy used to treat advanced Parkinson’s disease.

1. Pre-treatment/pre-operative period (from acceptance of receiving therapy to hospitalization^a)
• Specialist visits • Hospitalization • Laboratory/diagnostic tests	• Additional visits to each specialist due to the therapy (neurosurgery, psychiatry…; not due to Parkinson’s disease progression) • Y/N, service and length of stay • Y/N, number per type
2. Procedure/treatment administration (from patient’s hospitalization to discharge^a)
• Hospitalization • Procedure administration time • Specialists in the surgery room • Material (devices, disposable materials) • Laboratory/diagnostic tests • Anti-Parkinsonian treatment^b • Complications	• Y/N, service and length of stay • Hours/minutes • Number per each type (Specialized Nurse, Anaesthesiologist, etc.) • Number per each type • Y/N, number per type • Average reduction rate in anti-Parkinsonian drug use • Y/N, resource needs
3. Follow-up period: patient’s discharge^a to Month 6
• Specialist and urgency visits • Hospitalization • Laboratory/diagnostic tests • Complications • Anti-Parkinsonian treatment^b pharmacological treatment (non-anti-Parkinsonian drugs)	• Number per each type (neurosurgery, psychiatry, etc.) • Y/N, service and length of stay • Number per each type (x-ray, MRI, etc.) • Y/N, resource needs • Average reduction rate in anti-Parkinsonian drug use
4. Follow-up period: from Month 6 to Year 5
• Specialist and urgency visits	• Number per each type (neurosurgery, psychiatry, etc.)
• Hospitalization	• Y/N, service and length of stay
• Laboratory/diagnostic tests	• Number per each type (x-ray, MRI, etc.)
• Complications	• Y/N, resource needs
• Anti-Parkinsonian treatment from month 6 to year 5^b	• Average reduction rate in anti-Parkinsonian drug use
• DBS battery replacement^c	• When the replacement is done and description of all the resources needed

DBS, deep brain stimulation.

^aAlthough the terms hospitalization and discharge are used to determine the main different phases, these therapies can be administrated in an Outpatient Hospital Service. This data was also collected in the HRQ.

^bIn addition to the pharmacological cost of the evaluated therapies, the use of other anti-Parkinsonian drugs was compared before and after the procedure administration to analyse potential savings.

^cFor DBS, the battery replacement of the device was taken into account at year 5.

Table 2.  Sensitivity analysis.

Scenarios	Min value	Max value
1. No cost of anti-Parkinsonian drugs Costs of anti-Parkinsonian drugs were not considered (i.e. €0)
2. Costs of anti-Parkinsonian drugs (€/day) Costs were applied by extracting their values from published studies38, with a minimum (€9.38) and maximum (€55.05) patient daily cost for anti-Parkinsonian drugs.	€9.38	€55.05
3. Discount rate As recommended in the economic evaluation guidelines30, results were discounted applying a minimum (0%) and a maximum (5%) discount rate.	0%	5%
4. Two replacements of the DBS neurostimulator in 5 years According to clinical experience, battery replacement for non-rechargeable DBS neurostimulators is generally required between the fourth and fifth year11,32 depending on the programme settings tailored by patients. In this scenario, results were tested considering two battery replacements over the 5-year period.
5. Type of DBS neurostimulator The costs of the most recent DBS stimulators were included in the analysis, instead of the cost of the traditional non-rechargeable dual channel stimulator	Non-rechargeable, dual channel implantable neurostimulator for DBS^a	(a) Rechargeable, dual channel implantable neurostimulator for DBS that is suitable for patients with high energy needs who are willing and who able to keep their system recharged.^b (b) Smaller non-rechargeable, dual channel implantable neurostimulator for DBS that is suitable for patients with moderate energy needs^b
6. Reduction of CDLCI and CSAI costs—breakeven point Two univariate sensitivity analyses were performed in order to find the breakeven point, defined as the reduction of CSAI and CDLCI therapies drug acquisition costs necessary to obtain the same 5 year mean cost as DBS

DBS, deep brain stimulation; CDLCI, continuous duodenal levodopa-carbidopa infusion; CSAI, continuous subcutaneous infusion of apomorphine.

^aThe Medtronic Kinetra® neurostimulator is a legacy, non-rechargeable, dual channel implantable neurostimulator for deep brain stimulation (DBS).

^b(a) The Medtronic Activa® RC neurostimulator is a rechargeable, dual channel implantable neurostimulator for DBS that is suitable for patients with high energy needs who are willing and who able to keep their system recharged; (b) the Medtronic Activa® PC neurostimulator is a smaller non-rechargeable, dual channel implantable neurostimulator for DBS that is suitable for patients with moderate energy needs.

Table 3.  Cumulative use of resources during the 5-year follow-up period (average values).

Resource use	DBS	CDLCI	CSAI
Average number of medical visits
Surgeon	0.00	0.14	0.00
Gastroenterologist	0.00	2.47	0.00
Psychiatrist	0.14	0.14	1.17
Nurses	2.37	26.35	17.53
Anaesthetist	0.71	0.43	0.00
Neuropsychologist	0.86	0.86	3.67
Dermatologist	0.00	0.00	1.31
Neurosurgeon	12.17	0.31	0.00
Neurologist	19.98	24.75	28.71
Emergency room	0.09	1.68	1.07
Average hospitalization days
Neurology unit	5.46	12.73	6.41
Neurosurgery unit	5.04	1.02	0.11
Outpatient care unit	0.00	1.71	0.00
Intensive care unit	0.93	0.06	0.00
Average number of diagnostic tests
Blood tests	3.43	3.99	2.08
Electrocardiography	2.00	2.31	0.59
Computerized tomography (abdominal + head)	1.84	0.14	0.00
Endoscopy	0.00	0.21	0.00
Abdominal X-ray	2.12	7.56	0.11
Thorax X-ray	0.00	0.57	0.00
MRI	1.51	0.29	0.00
Coombs Test	0.00	0.00	0.67
Type of anaesthesia: number of times required on average
Local anaesthesia	0.94	0.44	0.00
General anaesthesia	2.00	0.20	0.00
Sedation	0.86	0.82	0.00
Average resources related to surgery (hours)
Operating room	10.20	0.00	0.00
Endoscopy room	0.00	2.80	0.00
Anaesthesiologist	13.70	2.05	0.00
Gastroenterologist	0.00	3.58	0.00
Surgeon/Neurosurgeon/Neurologist	26.61	0.00	1.00
Radiologist	0.00	0.14	0.00
Nurse	14.18	7.69	1.00
Endoscopist	0.00	1.34	0.00
Neurophysiologist	1.57	0.57	0.00
Surgeon’s Assistant	1.11	0.00	0.00
Psychologist	0.86	0.00	0.00
Therapy: number of items required on average
Duodopa: number of cartridges (cartridge 0.5/2 g/100 ml)	0.00	1752.26	0.00
Apomorphine: number of ampoules (ampoules 50 mg/5 ml)	0.00	0.00	3038.49
DBS neurostimulator	1.70	0.00	0.00
Electrodes	2.00	0.00	0.00
Extensions	2.00	0.00	0.00
Days of antiparkinsonian treatment^38	985.74	903.15	1123.46
Silicone patches	0.00	0.00	1.70

DBS, deep brain stimulation; CDLCI, continuous duodenal levodopa-carbidopa infusion; CSAI, continuous subcutaneous apomorphine infusion.

Table 4.  Unit costs of healthcare resources included in the HRQ (€, 2010).

Resource	Average unit cost (€)
Visits to specialists
Surgery	47.95
Gastroenterologist	78.87
Psychiatrist	40.38
Nurses	20.56
Anaesthetist	39.38
Neuropsychologist	91.09
Dermatologist	28.93
Neurosurgeon	77.94
Neurologist	91.09
Urgencies/emergency room	112.50
Rheumatologist	79.95
Hospitalization (cost/day)
Neurology	272.44
Neurosurgery	496.28
Outpatient Care	167.50
Intensive care unit (ICU)	1,085.81
Gastroenterology	307.61
Diagnostic tests
Laboratory tests	10.51
Electrocardiogram	18.97
Abdominal CT	124.83
Endoscopy	35.69
Abdominal X-ray	13.01
Thorax X-ray	19.54
Magnetic resonance	187.17
Cranial tomography	256
Coombs test	10.51
Electromyography	163.98
Ultrasound	11.46
Resources related to surgery
Operating room (cost/hour)	547.83
Endoscopy room (cost/hour)	375.96
Local anaesthesia	47.20
General anaesthesia	188.64
Sedation	47.20
Anaesthetist (cost/hour)	34.14
Gastroenterologist (cost/hour)	37.94
Surgeon (cost/hour)	41.50
Radiologist (cost/hour)	37.94
Nurse (cost/hour)	19.47
Endoscopist (cost/hour)	37.94
Neurophysiology (cost/hour)	41.5
Surgeon’s assistant (cost/hour)	37.94
Psychologist (cost/hour)	37.94
Cost related to therapies Continuous duodenal levodopa/carbidopa infusion (20/5 mg/ml, pack with 7 intestinal gel cartridges of 100 ml) Apomorphine (5 ampoules of 10 mg/ml) DBS system Silicone patches (patches 3 units for 20 days) Pharmacological cost/day anti-Parkinsonian treatment	756^a 151.75^a 17,163.6^b 10.69^a 38.9^c

DBS, deep brain stimulation.

^aRetail prices extracted from Official Database of Medicines in http://www.portalfarma.com (taxes included).

^bOfficial fees provided by Medtronic Ibérica S.A. (taxes included). The system included two electrodes, the extension wires, and the dual program neurostimulator (Kinetra®). In the sensitivity analysis, the costs of the new DBS family Activa® PC and Activa® RC were included, instead of the cost of Kinetra®: average unit costs of DBS system with Activa PC®: €19,555.5; Average costs per patient of DBS system with Activa RC®: €29,605.9. These systems also included two electrodes, the extension wires, and the dual program neurostimulator (Activa PC® or Activa RC®). In the DBS family Activa® RC, the charger costs was also included.

^cAverage anti-Parkinsonian pharmacological treatment cost per day38.

Table 5.  Results of the baseline scenario expressed as mean ± standard error. Costs per patient (€, 2010).

Phases	Average costs
	DBS (n = 7)^a	CDLCI (n = 9)^a	CSAI (n = 7)^a
1. Pre-treatment period to hospitalization^b	1141 ± 411	1705 ± 357	1231 ± 267
2. Hospitalization period to discharge^b	27,236 ± 3105^c	3165 ± 501^c	785 ± 197^c
3. Discharge^b to 6 months post-op	4768 ± 918^c,d	25,521 ± 2381^c	12,094 ± 2158^c,d
4. From month 6 to year 5	54,869 ± 4190^c,d	203,596 ± 8737^c	127,284 ± 9184^c,d
Total cost per 5 years	88,014 ± 2580^c,d	233,986 ± 10,552^c	141,393 ± 9945^c,d
Average cost per year	17,603 ± 516^c,d	46,797 ± 2110^c	28,279 ± 1989^c,d

DBS, deep brain stimulation; CDLCI, continuous duodenal levodopa-carbidopa infusion; CSAI, continuous subcutaneous infusion of apomorphine.

^an = number of expert observations collected for the specific therapy.

^bAlthough the terms hospitalization and discharge are used to determine the main different phases, these therapies can be administrated in an Outpatient Hospital Service.

^cComparison of the three therapies (p < 0.05).

^dDBS vs CSAI comparison (p < 0.05).

Figure 1.  Cumulative annual costs for deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous infusion of apomorphine (CSAI) (€, 2010). * All differences were statistically significant (p < 0.05) for multiple comparisons (among the three therapies) and for the DBS vs CSAI comparison (p < 0.05).

Figure 2.  Costs distribution of deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous infusion of apomorphine (CSAI) over the 5 year period (€, 2010).

Table 6.  Results of the bootstrap analysis.* Results are expressed as median (mean; 2.5 percentile; 97.5 percentile).

Phases	DBS	CDLCI	CSAI
1. Pre-treatment period hospitalization	1143 (1155; 1021; 1570)	1700 (1705; 1584; 2041)	1231 (1224; 1134; 1495)
2. Hospitalization period to discharge	27,319 (27,285; 26,412; 29,762)	3175 (3181; 3003; 3717)	786 (790;717;999)
3. Discharge post-op to 6 months	4757 (4782; 4514; 5612)	25,551 (25,649; 24,760; 28,176)	12,083 (12,100;11,410;14,158)
4. From month 6 to year 5	54,738 (54,786; 53,502; 58,512)	203,522 (203,518; 200,647; 212,420)	127,226 (126,960; 123,839; 135,635)
Total cost per 5 years	88,045 (88,009; 86,441; 92,398)	233,984 (234,054; 231,045; 243,091)	141,234 (141,076; 137,817; 149,905)

*The primary benefit of a bootstrap technique is that it is a non-parametric technique, so requires no assumptions as to the shape of the sampling distribution of the statistic of interest. Using the bootstrap approach, repeated random samples of the same size (in this case, the sample size was 50), as the original sample are drawn with replacement from the data. As such, the fact that an observation has been selected for inclusion in a re-sample does not preclude it from being selected again for the same re-sample. The statistic of interest is calculated from each re-sample, and these bootstrap estimates of the original statistic are then used to build up an empirical distribution for the statistic. The number of bootstrap re-samples, B, required depends on the application, but typically B should be at least 1000 when the distribution is to be used to construct confidence intervals.

Table 7.  Results of the sensitivity analysis (average ± standard error) (€, 2010). The results show 5-year total costs.

Scenarios	Average costs per patient (€ 2010)
	DBS	CDLCI	CSAI
Main analysis	88,014 ± 2580^a b	233,986 ± 10,552^a	141,393 ± 9945^a b
1. Without including the costs of anti-Parkinsonian drugs	50,061 ± 4480^a b	200,342 ± 2526^a	96,095 ± 7155^a b
2. Costs of oral anti-Parkinsonian drugs Min daily cost €9.38 Max daily cost €55.05	59,206 ± 3167^a b 103,730 ± 4786^a b	208,448 ± 3966^a 247,918 ± 14,348^a	107,010 ± 7515^a b 160,150 ± 11,772^a b
3. Discount rate Min 0% Max 5%	90,251 ± 2757^a b 86,639 ± 2473^a b	247,645 ± 11,130^a 225,724 ± 10,203^a	149,932 ± 10,546^a b 135,228 ± 9582^a b
4. Replacement cycle: 2 replacements considered in the 5-year period	101,260 ± 2580^a b	233,986 ± 10,552^a c	141,393 ± 9945^a b c
5. Cost of next generation non-rechargeable stimulator Cost of next generation rechargeable stimulator	91,960 ± 2461^a b 82,950 ± 2850^a b	233,986 ± 10,552^a c	141,393 ± 9945^a b c
6. Progressive reduction of CDLCI and CSAI pharmacological costs to reach the breakeven point.		A 78.5% reduction in CDLCI cost is needed to obtain the same 5-year total costs results as DBS	A 57.2% reduction in Apomorphine is needed to obtain the same 5-year total costs results as DBS

DBS, deep brain stimulation; CDLCI, continuous duodenal levodopa-carbidopa infusion; CSAI, continuous subcutaneous apomorphine infusion.

^aComparison of the three therapies (p < 0.05).

^bDBS vs CSAI comparison (p < 0.05).

^cSame results as main analysis.

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