Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database.

AIM: Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. MATERIALS AND METHODS: We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. RESULTS: Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. LIMITATIONS: Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. CONCLUSIONS: After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

For some people with epilepsy, medications do not work very well. For these people, other treatment options exist. One such treatment is neurostimulation. There are three types of neurostimulators­vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). All three devices are known to reduce seizures in patients who have tried several medications. However, it is not known how these devices impact the costs of care. We compared the use and costs of medical care over 2 years between patients who got VNS and those who got RNS/DBS. Before comparing the groups, we made sure that they were balanced. Patients who got VNS were less likely than patients who got RNS/DBS to go to the hospital during the follow-up period. Patients who got VNS also had lower healthcare costs than patients who got RNS/DBS during follow-up. These differences were seen for all medical care costs. These differences also were seen in the costs of care for epilepsy. Our results suggest that the use of VNS is associated with fewer hospitalizations than RNS/DBS, and also that use of VNS is associated with lower healthcare costs than RNS/DBS.

Vagus nerve stimulation with tachycardia detection provides additional seizure reduction compared to traditional vagus nerve stimulation.

PURPOSE: This study investigates the clinical and cost effectiveness of switching from traditional vagus nerve stimulation (VNS) to responsive VNS (rVNS), which has an additional ictal tachycardia detection and stimulation (AutoStim) mode. METHODS: Retrospective chart review was used to collect data from patients with medically refractory epilepsy who underwent generator replacements. Patients with confounding factors such as medication changes were excluded. Vagus nerve stimulation parameters, seizure frequency, and healthcare costs were collected for the 1-year period following generator replacement with the rVNS device. RESULTS: Documented seizure frequency was available for twenty-five patients. After implant with rVNS, 28% of patients had an additional ≥50% seizure reduction. There was a significant decrease in the average monthly seizure count (p = 0.039). In patients who were not already free of disabling seizures (n = 17), 41.2% had ≥50% additional seizure reduction. There was no difference in healthcare costs during the 1-year follow-up after the rVNS implant compared with one year prior. CONCLUSIONS: Ictal tachycardia detection and stimulation provided a significant clinical benefit in patients who were not free of disabling seizures with treatment from traditional VNS. There was no additional increase in healthcare costs during the first year after device replacement.

Analysis of pharmacotherapy regimen and costs in patients with drug-resistant epilepsy following vagus nerve stimulation therapy: a single-center study (Poland).

Approximately 30-40% of patients with drug-resistant epilepsy (DRE) who underwent vagus nerve stimulator (VNS) implantation achieve above 50% reduction in seizure frequency. VNS proves effective in reducing frequency of seizures in DRE patients, when combined with antiepileptic drugs (AEDs). This raises a question whether improvement of clinical parameters is achieved with VNS only or relies on combined therapy with AEDs. The aim of the study was the analysis of impact of VNS on clinical recovery of patients with DRE and the analysis of pharmacotherapy costs and drug regimen following VNS implantation in DRE patients. The study included all the patients who had VNS implanted at our department in the years 2014-2018. The patients would be followed up for 2 years after the VNS implantation date. The most commonly used drugs included levetiracetam, lacosamide, valproate, oxcarbazepine, and topiramate. Average cost of AEDs in year 1 following VNS implantation was between EUR 15.53 (CLB) and EUR 545.52 (TGB) and in year 2 between EUR 13.51 (NTZ) and EUR 779.44 (LAC). The greatest number of seizures affected the group of patients treated with three drugs. A statistically significant improvement in seizure frequency was observed in the group of patients treated with two and three drugs. With the rising costs of healthcare, the importance of economic efficiency is becoming increasingly relevant. VNS is a reasonable option for saving money in the healthcare system while ensuring measurable clinical and therapeutic outcomes over the long term.

Economic and clinical evaluation of vagus nerve stimulation therapy.

OBJECTIVES: The medical and social care of drug-resistant epilepsy (DRE) entails significant costs. Approximately 30 to 40 percent of patients with DRE who underwent vagus nerve stimulator (VNS) implantation achieve an above 50 percent reduction in seizure frequency. The study objective was to analyze the effect of VNS on clinical effects improvement and therapy cost reduction in patients with DRE over a 2-year follow-up period. The second purpose of the study was to compare average costs of VNS treatment of patients with DRE in selected countries, taking into account the purchasing power parity. MATERIALS AND METHODS: The study included all the patients who had VNS implanted at our department between 2014 and 2018. Data on clinical events and medical costs were collected prospectively and obtained from medical documentation. We also reviewed relevant literature on costs of VNS therapy in patients with DRE from the last 18 years. RESULTS: Resource utilization and epilepsy-related events were reduced during the follow-up period compared to the baseline. Average total cost was estimated at EUR 7703.59 in year 1 and at EUR 7108.38 in year 2 following VNS implantation. Average direct costs of VNS treatment of patients with DRE over the last 18 years varied between the countries and ranged from EUR 24 790.43 in the United States to EUR 64.84 in the United Kingdom. CONCLUSION: Vagus nerve stimulator is a cost-effective therapy yielding measurable clinical and therapeutic outcomes over the long term. Moreover, the analysis contained in this review highlights the poor consensus of methodological approaches.

Cost-effectiveness of noninvasive vagus nerve stimulation for acute treatment of episodic migraine and role in treatment sequence strategies.

Migraine affects 15% of the population in the United States and is associated with comorbidities, with an estimated economic burden of $78 billion annually. GammaCore is used adjunctively with current standard of care and abortive medications and has shown to be superior in acute treatment of episodic migraine compared to sham. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analyses for 2 hypothetical scenarios: a primary model for treatment options gammaCore plus standard of care compared to standard of care alone for acute treatment of migraine; and a secondary model for treatment sequence strategies where acute treatment with gammaCore or standard of care each prior to erenumab prevention compared to initiating erenumab prevention with no prerequisite. The time horizon for the model is 1 year, using a payer perspective. GammaCore plus standard of care arm was dominant over standard of care alone in the primary model. The mean costs for gammaCore plus standard of care arm and standard of care individually were $9678 and $10,010, respectively. The mean quality of life-years for gammaCore plus standard of care arm and standard of care alone were 0.67, and 0.63, respectively. For the secondary model, the mean costs for gammaCore followed by erenumab, standard of care followed by erenumab and initiating with erenumab with no prior gammaCore or standard of care treatment were $10,678, $11,583, and $13,766. The corresponding mean for quality of life-years were 0.70, 0.67, and 0.65, respectively. For gammaCore dominance, ie, in this scenario, patients were more satisfied on gammaCore, to not need erenumab for preventative therapy lower mean costs and represents savings for payers. This was driven by efficacy, improvement in quality of life, and reduction in costs of care associated with successful treatment of migraine attacks. These findings provide new economic evidence to support value forcoverage for gammaCore.

Non-invasive vagus nerve stimulation for treatment of cluster headache: early UK clinical experience.

BACKGROUND: Evidence supports the use of non-invasive vagus nerve stimulation (nVNS; gammaCore®) as a promising therapeutic option for patients with cluster headache (CH). We conducted this audit of real-world data from patients with CH, the majority of whom were treatment refractory, to explore early UK clinical experience with nVNS used acutely, preventively, or both. METHODS: We retrospectively analysed data from 30 patients with CH (29 chronic, 1 episodic) who submitted individual funding requests for nVNS to the National Health Service. All patients had responded to adjunctive nVNS therapy during an evaluation period (typical duration, 3-6 months). Data collected from patient interviews, treatment diaries, and physician notes were summarised with descriptive statistics. Paired t tests were used to examine statistical significance. RESULTS: The mean (SD) CH attack frequency decreased from 26.6 (17.1) attacks/wk. before initiation of nVNS therapy to 9.5 (11.0) attacks/wk. (P < 0.01) afterward. Mean (SD) attack duration decreased from 51.9 (36.7) minutes to 29.4 (28.5) minutes (P < 0.01), and mean (SD) attack severity (rated on a 10-point scale) decreased from 7.8 (2.3) to 6.0 (2.6) (P < 0.01). Use of abortive treatments also decreased. Favourable changes in the use of preventive medication were also observed. No serious device-related adverse events were reported. CONCLUSIONS: Significant decreases in attack frequency, severity, and duration were observed in these patients with CH who did not respond to or were intolerant of multiple preventive and/or acute treatments. These real-world findings complement evidence from clinical trials demonstrating the efficacy and safety of nVNS in CH.

Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.

INTRODUCTION: The objective was to estimate, from the perspective of a managed care organization in the United States, the budget impact and effect on health outcomes of expanded use of vagus nerve stimulation [VNS (VNS Therapy®)] among patients aged ≥ 12 years with drug-resistant epilepsy (DRE) with partial-onset seizures. METHODS: An Excel model was developed to compare the costs of continued anti-epileptic drug (AED) treatment with the costs of VNS plus AED treatment. The number of people eligible for VNS was estimated using published prevalence data and an estimate of the percentage of eligible patients currently without VNS. Costs included VNS device, placement, programming, and battery changes; adverse events associated with VNS (cough, voice alteration, device removal resulting from surgical site infection); AEDs; and seizure-related costs affected by seizure frequency, which affects resource utilization (i.e., hospitalizations, emergency department visits, neurologist visits). To estimate the potential savings with VNS due to a reduction in seizure frequency, the budget impact model uses the results of an underlying Markov model to estimate seizure-related costs by seizure frequency. Transitions occurred among four health states, defined by number of seizures per month (i.e., seizure-free, ≤ 1, > 1 to < 10, ≥ 10) on a 3-month cycle based on published clinical trials and registry data. RESULTS: VNS resulted in an estimated net cost savings, on average, over 5 years, due to the expected reduction in seizure frequency. The initial cost of the VNS device, placement, and programming was estimated to be offset 1.7 years after VNS device placement. Reductions in hospitalizations were the main contributor to the cost savings with VNS. CONCLUSIONS: VNS is a proven intervention that offers a long-term solution for patients with DRE by reducing seizure frequency, which leads to lower resource utilization and lower costs. FUNDING: LivaNova PLC.

Review of non-invasive vagus nerve stimulation (gammaCore): efficacy, safety, potential impact on comorbidities, and economic burden for episodic and chronic cluster headache.

The FDA has cleared gammaCore (non-invasive vagus nerve stimulator [nVNS]) for the treatment of episodic cluster headache (eCH). With the exception of subcutaneous sumatriptan, all other treatments are used off label and have many limitations. The FDA approval process for devices differs from that of drugs. We performed a review of the literature to evaluate new evidence on various aspects of gammaCore treatment and impact. The ACute Treatment of Cluster Headache Studies (ACT1 and ACT2), both double-blind sham-controlled randomized trials, did not meet the primary endpoints of the trials but each demonstrated significant superiority of gammaCore among patients with eCH. In ACT1, gammaCore resulted in a higher response rate (RR) (RR, 3.2; 95% CI, 1.6-8.2; P = .014), higher pain-free rate for >50% of attacks (RR, 2.3; 95% CI, 1.1-5.2; P = .045), and shorter duration of attacks (mean difference [MD], -30 minutes; P <.01) compared with the sham group. In ACT2, gammaCore resulted in higher odds of achieving pain-free attacks in 15 minutes (OR, 9.8; 95% CI, 2.2-44.1; P = .01), lower pain intensity in 15 minutes (MD, -1.1; P <.01), and higher rate of achieving responder status at 15 minutes for ≥50% of treated attacks (RR, 2.8; 95% CI, 1.0-8.1; P = .058) compared with the sham group. The PREVention and Acute Treatment of Chronic Cluster Headache (PREVA) study also demonstrated that gammaCore plus standard of care (SOC) was superior to SOC alone in patients with chronic cluster headache (CH). Medical costs, pharmacy refills, and pharmacy costs were higher in patients coded for CH in claims data compared with controls with nonheadache codes. gammaCore is easy to use, practical, and safe; delivery cannot be wasted; and patients prefer using gammaCore compared with SOC. The treatment improves symptoms and reduces the need for CH rescue medications. Current US reimbursement policies, which predate nVNS and are based on expensive, surgically implanted, and permanent implanted vagus nerve stimulation (iVNS), need to be modified to distinguish nVNS from iVNS. gammaCore, cleared by the FDA in April 2017, provides substantial value to patients and also to payers. There is sufficient evidence to support the need to modify current reimbursement policies to include coverage for gammaCore (nVNS) for eCH.

Cost-effectiveness of gammaCore (non-invasive vagus nerve stimulation) for acute treatment of episodic cluster headache.

Cluster headache is a debilitating disease characterized by excruciatingly painful attacks that affects 0.15% to 0.4% of the US population. Episodic cluster headache manifests as circadian and circannual seasonal bouts of attacks, each lasting 15 to 180 minutes, with periods of remission. In chronic cluster headache, the attacks occur throughout the year with no periods of remission. While existing treatments are effective for some patients, many patients continue to suffer. There are only 2 FDA-approved medications for episodic cluster headache in the United States, while others, such as high-flow oxygen, are used off-label. Episodic cluster headache is associated with comorbidities and affects work, productivity, and daily functioning. The economic burden of episodic cluster headache is considerable, costing more than twice that of nonheadache patients. gammaCore adjunct to standard of care (SoC) was found to have superior efficacy in treatment of acute episodic cluster headaches compared with sham-gammaCore used with SoC in ACT1 and ACT2 trials. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analysis of gammaCore adjunct to SoC compared with SoC alone for the treatment of acute pain associated with episodic cluster headache attacks. The model structure was based on treatment of acute attacks with 3 outcomes: failures, nonresponders, and responders. The time horizon of the model is 1 year using a payer perspective with uncertainty incorporated. Parameter inputs were derived from primary data from the randomized controlled trials for gammaCore. The mean annual costs associated with the gammaCore-plus-SoC arm was $9510, and mean costs for the SoC-alone arm was $10,040. The mean quality-adjusted life years for gammaCore-plus-SoC arm were 0.83, and for the SoC-alone arm, they were 0.74. The gammaCore-plus-SoC arm was dominant over SoC alone. All 1-way and multiway sensitivity analyses were cost-effective using a threshold of $20,000. gammaCore dominance, representing savings, was driven by superior efficacy, improvement in quality of life (QoL), and reduction in costs associated with successful and consistent abortion of episodic attacks. These findings serve as additional economic evidence to support coverage for gammaCore. Additional real-world data are needed to characterize the long-term impact of gammaCore on comorbidities, utilization, QoL, daily functioning, productivity, and social engagement of these patients, and for other indications.

A systematic review of economic evaluations of treatments for patients with epilepsy.

The increasing number of treatment options and the high costs associated with epilepsy have fostered the development of economic evaluations in epilepsy. It is important to examine the availability and quality of these economic evaluations and to identify potential research gaps. As well as looking at both pharmacologic (antiepileptic drugs [AEDs]) and nonpharmacologic (e.g., epilepsy surgery, ketogenic diet, vagus nerve stimulation) therapies, this review examines the methodologic quality of the full economic evaluations included. Literature search was performed in MEDLINE, EMBASE, NHS Economic Evaluation Database (NHS EED), Econlit, Web of Science, and CEA Registry. In addition, Cochrane Reviews, Cochrane DARE and Cochrane Health Technology Assessment Databases were used. To identify relevant studies, predefined clinical search strategies were combined with a search filter designed to identify health economic studies. Specific search strategies were devised for the following topics: (1) AEDs, (2) patients with cognitive deficits, (3) elderly patients, (4) epilepsy surgery, (5) ketogenic diet, (6) vagus nerve stimulation, and (7) treatment of (non)convulsive status epilepticus. A total of 40 publications were included in this review, 29 (73%) of which were articles about pharmacologic interventions. Mean quality score of all articles on the Consensus Health Economic Criteria (CHEC)-extended was 81.8%, the lowest quality score being 21.05%, whereas five studies had a score of 100%. Looking at the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), the average quality score was 77.0%, the lowest being 22.7%, and four studies rated as 100%. There was a substantial difference in methodology in all included articles, which hampered the attempt to combine information meaningfully. Overall, the methodologic quality was acceptable; however, some studies performed significantly worse than others. The heterogeneity between the studies stresses the need to define a reference case (e.g., how should an economic evaluation within epilepsy be performed) and to derive consensus on what constitutes "standard optimal care."

Socioeconomic evaluation of vagus stimulation: A controlled national study.

PURPOSE: We aimed to determine the health costs and social outcomes in terms of education, employment and income level after insertion of a vagus nerve stimulator (VNS) in patients with epilepsy. METHODS: This is a case-control study using Danish health care and socioeconomic register data. The analysis of the effect involved a comparison of the health care costs, occupation and income status of VNS-treated epilepsy patients with those of a control group of epilepsy patients who had a VNS implanted during the 12 months before the index date (pre-period) and during the two years after the index date (post-period). RESULTS: 101 patients who had undergone VNS implantation and 390 control patients were included. VNS implantation was associated with fewer inpatient admissions and emergency room visits and less frequent use of prescription medication compared with epilepsy patients without VNS implantation. VNS implantation was not associated with changes in occupational status (including employment and income). In fact, the number of people on disability pension increased during the period. CONCLUSIONS: VNS implantation in people with epilepsy is associated with reduced health care use, but not with occupational or social status.

Cost-utility analysis of competing treatment strategies for drug-resistant epilepsy in children with Tuberous Sclerosis Complex.

BACKGROUND: The management of drug-resistant epilepsy in children with Tuberous Sclerosis Complex (TSC) is challenging because of the multitude of treatment options, wide range of associated costs, and uncertainty of seizure outcomes. The most cost-effective approach for children whose epilepsy has failed to improve with first-line medical therapy is uncertain. METHODS: A review of MEDLINE from 1990 to 2015 was conducted. A cost-utility analysis, from a third-party payer perspective, was performed for children with drug-resistant epilepsy that had failed to improve with 2 antiseizure drugs (ASDs) and that was amenable to resective epilepsy surgery, across a time-horizon of 5years. Four strategies were included: (1) resective epilepsy surgery, (2) vagus nerve stimulator (VNS) implantation, (3) ketogenic diet, and (4) addition of a third ASD (specifically, carbamazepine). The incremental cost per quality-adjusted life year (QALY) gained was analyzed. RESULTS: Given a willingness-to-pay (WTP) of $100,000 per QALY, the addition of a third ASD ($6600 for a gain of 4.14 QALYs) was the most cost-effective treatment strategy. In a secondary analysis, if the child whose epilepsy had failed to improve with 3 ASDs, ketogenic diet, addition of a fourth ASD, and resective epilepsy surgery were incrementally cost-effective treatment strategies. Vagus nerve stimulator implantation was more expensive yet less effective than alternative strategies and should not be prioritized. CONCLUSIONS: The addition of a third ASD is a universally cost-effective treatment option in the management of children with drug-resistant epilepsy that has failed to improve with 2 ASDs. For children whose epilepsy has failed to improve with 3 ASDs, the most cost-effective treatment depends on the health-care resources available reflected by the WTP.

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control.

The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-invasive electrical stimulation of this nerve through the skin may offer a simple, cost-effective alternative to the established method of vagus nerve stimulation (VNS), which requires a surgical procedure and has generated mixed results in a number of clinical trials for heart failure. This review discusses the available evidence in support of modulating cardiac activity using this strange auricular nerve.

Cost-effectiveness analysis of non-invasive vagus nerve stimulation for the treatment of chronic cluster headache.

BACKGROUND: Cluster headache (CH) is a debilitating condition that is generally associated with substantial health care costs. Few therapies are approved for abortive or prophylactic treatment. Results from the prospective, randomised, open-label PREVA study suggested that adjunctive treatment with a novel non-invasive vagus nerve stimulation (nVNS) device led to decreased attack frequency and abortive medication use in patients with chronic CH (cCH). Herein, we evaluate whether nVNS is cost-effective compared with the current standard of care (SoC) for cCH. METHODS: A pharmacoeconomic model from the German statutory health insurance perspective was developed to estimate the 1-year cost-effectiveness of nVNS + SoC (versus SoC alone) using data from PREVA. Short-term treatment response data were taken from the clinical trial; longer-term response was modelled under scenarios of response maintenance, constant rate of response loss, and diminishing rate of response loss. Health-related quality of life was estimated by modelling EQ-5D™ data from PREVA; benefits were defined as quality-adjusted life-years (QALY). Abortive medication use data from PREVA, along with costs for the nVNS device and abortive therapies (i.e. intranasal zolmitriptan, subcutaneous sumatriptan, and inhaled oxygen), were used to assess health care costs in the German setting. RESULTS: The analysis resulted in mean expected yearly costs of €7096.69 for nVNS + SoC and €7511.35 for SoC alone and mean QALY of 0.607 for nVNS + SoC and 0.522 for SoC alone, suggesting that nVNS generates greater health benefits for lower overall cost. Abortive medication costs were 23 % lower with nVNS + SoC than with SoC alone. In the alternative scenarios (i.e. constant rate of response loss and diminishing rate of response loss), nVNS + SoC was more effective and cost saving than SoC alone. CONCLUSIONS: In all scenarios modelled from a German perspective, nVNS was cost-effective compared with current SoC, which suggests that adjunctive nVNS therapy provides economic benefits in the treatment of cCH. Notably, the current analysis included only costs associated with abortive treatments. Treatment with nVNS will likely promote further economic benefit when other potential sources of cost savings (e.g. reduced frequency of clinic visits) are considered. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01701245 , 03OCT2012.

Impact of vagus nerve stimulation on secondary care burden in children and adults with epilepsy: Review of routinely collected hospital data in England.

PURPOSE: We evaluated the long-term medical and economic benefits of vagus nerve stimulation (VNS) therapy for 704 adults and children with epilepsy. A pre-post analysis was conducted using Hospital Episode Statistics (HES) data (April 2008-July 2014). Seven hundred and four patients with epilepsy diagnoses (ICD-10 G40.x or G41.x), one or more procedures for vagus nerve stimulator implantation, and six or more months of available HES data pre- and post-VNS were selected. The pre-VNS period averaged 39.1 months. The post-VNS period extended from implantation to device removal, death, or study end (up to six years), with a mean duration of 36.4 months. Incidence rate ratios (IRRs) and cost differences (£2014) were estimated. Mean age was 28.3 years. RESULTS: Inpatient admissions decreased post-VNS compared with pre-VNS (adjusted IRR=0.81, P<0.001). Overall, outpatient consultations increased post-VNS compared with pre-VNS (adjusted IRR=1.34, P<0.001). However, outpatient consultations exhibited a decreasing trend in the post-VNS period (adjusted IRR=0.96, P<0.001), suggesting that much of the increased outpatient activity in the post-VNS period relates to follow-up management of the VNS device in the immediate period following implantation, with comparable outpatient resource burden at 36 months post-VNS. No significant changes in clinical events were observed; however, average epilepsy-related medical costs were lower post-VNS than pre-VNS (adjusted cost difference -£110 quarterly, P=0.001). CONCLUSIONS: Vagus nerve stimulation is associated with increased outpatient resource utilization and decreased inpatient admissions, with a reduction in long-term epilepsy-related medical costs post-implantation.

Cost-effectiveness of the ketogenic diet and vagus nerve stimulation for the treatment of children with intractable epilepsy.

PURPOSE: The objective of this study was to estimate the expected cost-utility and cost-effectiveness of the ketogenic diet (KD), vague nerve stimulation (VNS) and care as usual (CAU), using a decision analytic model with a 5-year time horizon. METHODS: A Markov decision analytical model was constructed to estimate the incremental costs, quality-adjusted life years (QALYs) and successfully treated patient (i.e. 50% or more seizure reduction) of the treatment strategies KD, VNS and CAU, from a health care perspective. The base case considered children with intractable epilepsy (i.e. two or more antiepileptic drugs had failed) aged between 1 and 18 years. Data were derived from literature and expert meetings. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Our results suggest that KD is more effective and less costly, and thus cost-effective compared with VNS, after 12 months. However, compared to CAU, neither KD nor VNS are cost-effective options, they are both more effective but also more expensive (€346,899 and €641,068 per QALY, respectively). At 5 years, VNS is cost-effective compared with KD and CAU (€11,378 and €68,489 per QALY, respectively) and has a 51% probability of being cost-effective at a ceiling ratio of €80,000 per QALY. CONCLUSIONS: Our results suggest that on average the benefits of KD and VNS fail to outweigh the costs of the therapies. However, these treatment options should not be ignored in the treatment for intractable epilepsy in individual or specific groups of patients. There is a great need for high quality comparative studies with large patient samples which allow for subgroup analyses, long-term follow-up periods and outcome measures that measure effects beyond seizure frequency (e.g. quality of life). When this new evidence becomes available, reassessment of the cost-effectiveness of KD and VNS in children with intractable epilepsy should be carried out.

Vagus nerve stimulation therapy in a developing country: a long term follow up study and cost utility analysis.

PURPOSE: To evaluate clinical outcomes, quality-adjusted life years (QALY), cost effectiveness and cost utility associated with VNS therapy in children with refractory epilepsy in a developing country. METHODS: Retrospective review of all children who underwent VNS implantation at King Abdullah University Hospital and Jordan University Hospital in Jordan. RESULTS: Twenty eight patients (16 males) had implantation of the VNS therapy system between the years 2007 and 2011. Mean age at implantation was 9.4 years. Mean duration of epilepsy prior to implantation was 6.5 years. The most common seizure type was generalized tonic clonic seizures. Fifteen patients showed a 50% or more reduction in seizure frequency. There was a significant reduction in total number of seizures (p=0.002) and emergency room (ER) visits (p=0.042) after VNS therapy. Atonic seizures were more likely to respond than generalized tonic clonic seizures, p=0.034. Direct hospital costs prior to VNS implantation were analyzed in relation to ER visits and intensive care unit (ICU) admissions. Cost savings per patient did reduce the financial burden of the device by about 30%. There was a QALY gain per lifetime of 3.78 years for children and 1 year for adolescents. CONCLUSION: Response to VNS implantation in Jordan was favorable and similar to what has been previously reported. QALY gain and cost per QALY analysis were encouraging. Cost savings were related to reduction in seizure severity. In circumstances of limited resources as in developing countries, targeting patients with frequent utilization of health services would improve cost effectiveness.

Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis.

OBJECTIVE: The objective of this analysis was to evaluate the effectiveness of deep brain stimulation (DBS) and vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsy in adults and children. DATA SOURCES: A literature search was performed using MEDLINE, EMBASE, the Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 2007 until December 2012. REVIEW METHODS: Systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies (in the absence of RCTs) of adults or children were included. DBS studies were included if they specified that the anterior nucleus of thalamus was the area of the brain stimulated. Outcomes of interest were seizure frequency, health resource utilization, and safety. A cost analysis was also performed. RESULTS: The search identified 6 studies that assessed changes in seizure frequency after electrical stimulation: 1 RCT on DBS in adults, 4 RCTs on VNS in adults, and 1 RCT on VNS in children. The studies of DBS and VNS in adults found significantly improved rates of seizure frequency, but the study of VNS in children did not find a significant difference in seizure frequency between the high and low stimulation groups. Significant reductions in hospitalizations and emergency department visits were found for adults and children who received VNS. No studies addressed the use of health resources for patients undergoing DBS. Five studies reported on adverse events, which ranged from serious to transient for both procedures in adults and were mostly transient in the 1 study of VNS in children. LIMITATIONS: We found no evidence on DBS in children or on health care use related to DBS. The measurement of seizure frequency is self-reported and is therefore subject to bias and issues of compliance. CONCLUSIONS: Based on evidence of low to moderate quality, both DBS and VNS seemed to reduce seizure frequency in adults. In children, VNS did not appear to be as effective at reducing seizure frequency, but children had significantly fewer hospitalizations and ED visits after VNS implantation. Despite the considerable risks associated with these invasive procedures, long-term adverse events appear to be limited. PLAIN LANGUAGE SUMMARY: Electrical stimulation of specific areas of the brain is a procedure used to control epileptic seizures when more conventional treatments are not working. Most adults and children with epilepsy are able to control their seizures with medication, but for some patients, drugs are not effective and surgery to remove the part of the brain where the seizures start is not an appropriate option. This study looked at the research available on the effectiveness, safety, and cost of two types of electrical stimulation devices currently licensed for treatment of epilepsy for adults and children in Canada: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). Both approaches appear to be effective at reducing the frequency of seizures in adults. However, the evidence on DBS is limited to a single study with adults; we found no studies of DBS with children. Studies on VNS showed that both adults and children had fewer hospitalizations and emergency department visits after the procedure. Both procedures carry serious risks, but several longer-term studies have found that adverse events appear to be limited. The cost of VNS, including the process of assessing whether or not patients are good candidates for the procedure, is estimated to be about $40,000 per person (and higher for DBS because the device is more expensive and the operating time is longer). Of the 70,000 people in Ontario with epilepsy, about 1,400 (300 children and 1,110 adults) may be candidates for VNS to reduce their seizures.

Comparing the effects of cortical resection and vagus nerve stimulation in patients with nonlesional extratemporal epilepsy.

The main purpose of this retrospective study was to compare the effects of resective surgery (RESgr-26 patients) and vagus nerve stimulation (VNSgr-35 patients) on seizure frequency (2 and 5years after surgery) in patients with nonlesional extratemporal epilepsy (NLexTLE). We analyzed hospital admission costs directly associated with epilepsy (HACE) in both groups at the same follow-up. The decrease in seizure frequency from the preoperative levels, in both VNSgr and RESgr, was statistically significant (p<0.001). The seizure frequency reduction did not differ significantly between the follow-up visits for either group (p=0.221 at 2years and 0.218 at 5years). A significantly higher number of Engel I and Engel I+II patients were found in RESgr than in VNSgr at both follow-up visits (p=0.04 and 0.007, respectively). Using McHugh classification, we did not find statistically significant differences between both groups at both follow-up visits. Hospital admission costs directly associated with epilepsy/patient/year in both RESgr and VNSgr dropped significantly at 2- and 5-year follow-up visit and this reduction was not statistically different between RESgr and VNSgr (p=0.232). Both VNS and resective surgery cause comparably significant seizure reduction in NLexTLE. Resective surgery leads to a greater number of patients with excellent postoperative outcome (Engel I+II). The HACE reduction is statistically comparable between both groups.