An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug resistant epilepsy in the United States

Figures & data

Figure 1. Model structure for VNS + ASM group. ASM: anti-seizure medication; VNS: vagus nerve stimulation.

Figure 2. Model structure for ASM only group. ASM: anti-seizure medication; VNS: vagus nerve stimulation.

Table 1. Health-related quality of life values used in model.

Parameter	Corresponding seizure frequency group reported in Messori et al.^34	Mean utility^a	Range for DSA
0–50% reduction (no response)	10+ per month	0.66	0.65–0.67
50–74% reduction (responder)	2–9 per month	0.79	0.78–0.80
75–99% reduction (responder)	0–1 per month	0.91	0.90–0.92
100% reduction (seizure free)	0 seizures per year	0.96	0.95–0.97
Baseline for population^b		0.86^b	–

DSA: deterministic sensitivity analysis.

^aMean values displayed are as reported by or derived from the literature. These are used to understand the relative difference between model health states.

^bThis value represents the age- and gender ratio-adjusted baseline for “seizure free” patients to which the relative utility differences between health states should be applied³⁶.

Table 2. Summary of annual healthcare resource costs and utilization.

	Health state costs
Health care resource item	100% seizure freedom^a	75–99% seizure reduction^b	50–74% seizure reduction^c	<50% seizure reduction^d
Base level of seizures	0	243	287	506
ED visits	$0 (0.00)	$446 (0.61 [0.52–0.70])	$527 (0.72 [0.62–0.83])	$1,610 (2.21 [1.6–2.92])
Inpatient visits	$0 (0.00)	$15,401 (1.13 [0.96–1.30])	$18,206 (1.33 [1.13–1.53])	$75,309 (5.51 [3.98–7.29])
Outpatient neurologist visits	$156 (1.50 [1.28–1.73])	$1,087 (10.47 [8.90–12.04])	$1,285 (12.38 [10.52–14.23])	$2,337 (22.51 [16.26–29.77])
Total HCRU	$156	$16,933	$20,018	$79,256

ED: emergency department; HCRU: healthcare resource use.

^aAs reported by Kristian et al.²⁷.

^bInformed by the mean number of seizures of each response group from E03 and E05 (at 3 months follow up for response states, i.e. a 15% reduction in resource use from the 50–74% seizure reduction health state is assumed for each HCRU.

^cInformed by: Bernstein et al.⁴¹.

^dInformed by applying the lower estimate of the relative difference expected between “uncontrolled” and “controlled” epilepsy reported by a US study⁴². To note, Manjunath et al.⁴² did not define “hospitalization” and the ratio is applied uniformly to estimates in-patient admissions derived using data from Bernstein et al.⁴¹.

Table 3. Resource use and costs for VNS.

Parameter	Cost for base case	Source
Implantation procedure	$30,691	Includes Full system implant or replacement (Hospital) (CPT code: 64568; APC code: 5465) and Full system placement or replacement in facility settings (Surgery) (CPT code: 64568)^44.
VNS therapy device	$37,078	Cost of SenTiva generator^45. Cost applied in a scenario analysis.
Pre- and post-operative neurologist review	$54.33	Complex programming includes adjustment of more than three parameters in non-facility settings (CPT code: 95977)^44. $362 was applied for six outpatient reviews.
Explant procedure	$11,895	Surgical removal of generator or receiver in facility settings (CPT code 61888; APC code: 5463)^44. Costs associated with removal of generator or receiver in hospital and surgery setting (CPT code 61888)^44.
Replacement procedure	$21,455	Inclusive of surgical and hospitalization costs of Replacement of generator or receiver with connection to a single electrode array (CPT code 61885)^44.

APC: ambulatory payment classification; CPT: current procedural terminology; VNS: vagus nerve stimulation.

Table 4. Base-case cost effectiveness results.

Group	VNS + ASM	ASM only	Increment
Costs
Device cost sub-total	$39,824	$0	$39,824
Implantation	$31,017	$0	$31,017
Explantation	$210	$0	$210
Replacement	$8,596	$0	$8,596
ASM acquisition	$204,256	$204,256	$0
TRAEs costs	$141	$0	$141
Health state costs sub-total	$445,738	$595,380	-$149,643
Acute care	$9,429	$12,250	-$2,821
Inpatient	$420,958	$564,679	-$143,720
Outpatient	$15,350	$18,452	-$3,101
Total cost	$689,959	$799,637	-$109,678
Health outcomes
Life years	8.503	8.503	0
QALYs	6.051	5.666	0.385
Incremental outcomes
ICER (per QALY)	VNS dominates
Incremental net monetary benefit ($50,000 threshold)	$128,903
Incremental net health benefit ($50,000 threshold)	2.58

ASM: anti-seizure medication; ICER: incremental cost effectiveness ratio; QALY: quality-adjusted life year; TRAE: treatment-related adverse event; VNS: vagus nerve stimulation.

Figure 3. Deterministic sensitivity analysis—tornado diagram. ASM: anti-seizure medication; ED: Emergency Department; NMB: net monetary benefit; QALY: quality-adjusted life year; SMR: standardized mortality ratio; TRAE: treatment-related adverse event; VNS: vagus nerve stimulation. Notes. Where a parameter sensitivity analysis involved change to a single value, lower and upper bound values are shown on the diagram; ^¥lower or upper bound applied to the group of inputs informing the parameter simultaneously.

Table 5. Top 15 most sensitive parameters.

	iNMB
Parameter varied	Lower bound value	Upper bound value	Delta
Base-case	$128,903		N/A
Inpatient resource use^¥	$84,793	$180,973	$96,180
Probability of <50% seizure reduction for VNS in first cycle (0.74 [0.85–0.63])	$81,143	$176,663	$95,520
Explantation probabilities^¥	$131,810	$66,806	$65,004
Long term probabilities^¥	$106,732	$155,098	$48,366
VNS and ASMs clinical trial probabilities^¥	$151,421	$106,385	$45,036
Inpatient admission unit costs ($13,668 [$11,618–$15,719])	$107,345	$150,461	$43,116
ASM reduction with VNS (1.00 [0.85–1.15])	$146,934	$110,872	$36,061
Total implant-related cost ($31,017 [$26,365–$35,670])	$133,556	$124,250	$9,305
Health state utilities^¥	$130,162	$127,644	$2,519
Replacement cost ($21,781 [$18,514–$25,048])	$130,192	$127,614	$2,579
Outpatient resource use^¥	$127,738	$130,315	$2,577
ED resource use^¥	$127,998	$129,979	$1,981
TRAE probabilities^¥	$129,725	$127,941	$1,784
Neurologist outpatient visit unit cost ($104 [$88–$119])	$128,459	$129,347	$888
ED unit cost ($728 [$619–$837])	$128,480	$129,326	$846

ASM: anti-seizure medication; ED: emergency department; iNMB: incremental net monetary benefit; N/A: non-applicable; TRAE: treatment-related adverse event; VNS: vagus nerve stimulation.

Notes. Incremental net monetary benefit calculated using a threshold of $50,000 ((incremental benefit × threshold)−incremental cost).

^¥Lower or upper bound applied to the group of inputs informing the parameter simultaneously (please see supplement for additional information).

Figure 4. Probabilistic sensitivity analysis—scatter plot. ASM: anti-seizure medication; QALY: quality-adjusted life year; VNS: vagus nerve stimulation.

Messori A, Trippoli S, Becagli P, et al. Adjunctive lamotrigine therapy in patients with refractory seizures: a lifetime cost-utility analysis. Eur J Clin Pharmacol. 1998;53(6):421–427.

 PubMed Web of Science ®Google Scholar

Jiang R, Janssen MFB, Pickard AS. US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples. Qual Life Res. 2021;30(3):803–816.

 PubMed Web of Science ®Google Scholar

Kristian B, Wachtmeister K, Stefan F, et al. Retigabine as add-on treatment of refractory epilepsy–a cost-utility study in a Swedish setting. Acta Neurol Scand. 2013;127(6):419–426.

 PubMed Web of Science ®Google Scholar

Bernstein AL, Hess T. Vagus nerve stimulation therapy for pharmacoresistant epilepsy: effect on health care utilization. Epilepsy Behav. 2007;10(1):134–137.

 PubMed Web of Science ®Google Scholar

Manjunath R, Paradis PE, Parisé H, et al. Burden of uncontrolled epilepsy in patients requiring an emergency room visit or hospitalization. Neurology. 2012;79(18):1908–1916.

 PubMed Web of Science ®Google Scholar

LivaNova. VNS therapy codes. Data on file; 2022.

 Google Scholar

LivaNova. Price list. Data on file; 2022.

 Google Scholar