Cost-Effectiveness Analysis Between Sacral Neuromodulation and OnabotulinumtoxinA for the Treatment of Refractory Overactive Bladder in Women: A Systematic Review.

OBJECTIVE: We summarized the evidence evaluating the cost-effectiveness of sacral neuromodulation (SNM) versus onabotulinumtoxinA (BONT/A) in the treatment of refractory overactive bladder (OAB) among women. METHODS: We searched PubMed Medline (1946-2019), EMBASE (1947-2019), Web of Science (1900-2019), Clinical Trials.gov, reviewed references of included studies, and Cochrane subsets of CDSR, DARE, CENTRAL, and NHSEED. We included cost-utility and cost-effectiveness analyses or decision analysis comparing SNM versus BONT/A in women with nonneurogenic refractory OAB. Primary outcomes included incremental cost-effectiveness ratios (ICERs), reported as cost per quality-adjusted life year (QALY), which were abstracted or calculated. RESULTS: Five studies met the inclusion criteria. Three studies were industry supported. Two studies of high quality found BONT/A to be dominant over SNM (ICER range of $415,571/QALY at 5 years and $236,370/QALY at 10 years). This trend was further supported by a third study of high quality that favored BONT/A because SNM was not cost-effective (ICER, $116,427/QALY at 2 years). In contrast, 2 other studies of lower quality found that SNM was cost-effective or dominant in comparison to BONT/A (ICER range, $3,717/QALY to €15,226/QALY at 10 years). In general, models were sensitive to treatment duration, intervention setting, and lacked robust data on long-term outcomes. CONCLUSIONS: OnabotulinumtoxinA is more cost-effective for managing refractory OAB when compared with SNM. However, it remains unclear whether this finding holds true long term for what is considered a lifelong condition.

National Patterns of Filled Prescriptions and Third-Line Treatment Utilization for Privately Insured Women With Overactive Bladder.

OBJECTIVE: The aim of this study was to evaluate national patterns of care for women with overactive bladder (OAB) in an administrative data set and identify potential areas for improvement. METHODS: We performed an analysis using the OptumLabs Data Warehouse, which contains deidentified administrative claims data from a large national US health insurance plan. The study included women, older than 18 years, with a new OAB diagnosis from January 1, 2007, to June 30, 2017. We excluded those with an underlying neurologic etiology, with interstitial cystitis/painful bladder syndrome, were pregnant, or did not have continuous enrollment for 12 months before and after OAB diagnosis. Trends in management were assessed via the Cochran-Armitage test. Time to discontinuation among medications was compared using t test. RESULTS: Of 1.4 million women in the database during the study time frame, 60,246 (4%) were included in the study. Median age was 61 years [interquartile range (IQR), 50-73], and median follow-up was 2.6 years (IQR, 1.6-4.2). Overall, 37% were treated with anticholinergics, 5% with beta-3 agonists, 7% with topical estrogen, and 2% with pelvic floor physical therapy; 26% saw a specialist; and 2% underwent third-line therapy. Median time to cessation of prescription filling was longer for beta-3 agonists versus anticholinergics [median, 4.1 months (IQR, 1-15) vs 3.6 months (IQR, 1-10); P < 0.0001]. Use of third-line therapies significantly increased over the study time frame, from 1.1% to 2.2% (P < 0.0001). CONCLUSIONS: Most of the patients do not continue filling prescriptions for OAB medications, and a minority of patients were referred for specialty evaluation. Although third-line therapy use is increasing, it is used in a small proportion of women with OAB. Given these patterns, there may be underutilization of specialist referral and other OAB therapies.

Cost Effectiveness of Sacral Neuromodulation and OnabotulinumtoxinA in Managing Refractory Idiopathic Overactive Bladder.

Little information from clinical and modelled studies are available on cost effectiveness of OnabotulinumtoxinA and SNM for the treatment of idiopathic overactive bladder. We aimed to summarize the evidence in this regard from different healthcare systems. Seven studies from 5 countries were reviewed. Some modelled studies with a 10-year time frame showed that sacral neuromodulation became dominant long-term; others suggested OnabotulinumtoxinA was more cost effective at <5 years. There was considerable heterogeneity in the base case/sensitivity analysis and statistical modelling among the studies. Clinical studies with longer term follow-up will help determine cost effectiveness more accurately.

Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Real World Performance of Sacral Neuromodulation and OnabotulinumtoxinA for Overactive Bladder: Focus on Safety and Cost.

PURPOSE: We aimed to determine the real world safety and cost of third line overactive bladder therapies, including onabotulinumtoxinA and sacral neuromodulation. MATERIALS AND METHODS: We performed an all-inclusive, population based cohort study of third line therapies of overactive bladder (sacral neuromodulation or onabotulinumtoxinA) using the statewide surgical data captured in the New York Statewide Planning and Research Cooperative System. The main outcome measures were 30-day safety events, and 1 and 3-year health care utilization costs. Propensity score matching was done to control for confounding factors and comparative analyses of safety events were also performed. RESULTS: Our cohort included 2,680 patients, of whom 1,328 underwent sacral neuromodulation and 1,352 received onabotulinumtoxinA from January 1, 2013 through December 31, 2016. Average ± SD age was 61.7 ± 16.3 years and 82.7% of the patients were female. Sacral neuromodulation implantation led to re-intervention in 15.8% of cases within 1 year and in 26.1% at 3 years. In this comparative analysis patients who received onabotulinumtoxinA therapy were at higher risk for urinary tract infection, hematuria, urinary retention and an emergency room visit compared to those treated with sacral neuromodulation. The overall cost of onabotulinumtoxinA was lower than the cost of the sacral neuromodulation device (cost at 1 year $2,896 vs $15,343 and at 3 years $3,454 vs $16,189, each p <0.01). CONCLUSIONS: Sacral neuromodulation implantation was more expensive than onabotulinumtoxinA injection. However, patients who underwent sacral neuromodulation had a lower complication rate than patients treated with onabotulinumtoxinA. A quality improvement collective database must be created to track information on onabotulinumtoxinA and sacral neuromodulation treatment. This would help generate better performance and comparative data for patient and physician decision making.

Cost-Effectiveness of Sacral Neuromodulation versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: Results of the ROSETTA Randomized Trial.

PURPOSE: Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence. MATERIALS AND METHODS: Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p <0.01), persisting through 5 years ($36,550 [95% CI 34,787-38,309] vs $12,020 [95% CI 10,330-13,700], p <0.01). At 2 years there were no differences in mean reduction in urgency urinary incontinence episodes per day (-3.00 [95% CI -3.38 - -2.62] vs -3.12 [95% CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95% CI 1.34-1.44] vs 1.41 [95% CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost-effective relative to onabotulinumtoxinA is less than 0.025 for all willingness to pay values below $580,000 per QALY at 2 years and $204,000 per QALY at 5 years. CONCLUSIONS: Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency urinary incontinence compared to 200 units onabotulinumtoxinA.

Cost-effectiveness of overactive bladder treatments: from the US payer perspective.

AIM: To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB). METHODS: A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. RESULTS: Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC. CONCLUSION: Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

[How to convince the head of department and managing director of the importance of specialised headache clinics]. / Como convencer al jefe de servicio y al gerente de la importancia de las unidades/consultas especializadas de cefaleas.

In spite that headache is, by far, the most frequent reason for neurological consultation and that the diagnosis and treatment of some patients with headache is difficult, the number of headache clinics is scarce in our country. In this paper the main arguments which should allow us, as neurologists, to defend the necessity of implementing headache clinics are reviewed. To get this aim we should first overcome our internal reluctances, which still make headache as scarcely appreciated within our specialty. The facts that more than a quarter of consultations to our Neurology Services are due to headache, that there are more than 200 different headaches, some of them actually invalidating, and the new therapeutic options for chronic patients, such as OnabotulinumtoxinA or neuromodulation techniques, oblige us to introduce specialised headache attendance in our current neurological offer. Even though there are no definite data, available results indicate that headache clinics are efficient in patients with chronic headaches, not only in terms of health benefit but also from an economical point of view.

TITLE: Como convencer al jefe de servicio y al gerente de la importancia de las unidades/consultas especializadas de cefaleas.A pesar de que la cefalea es, con diferencia, el principal motivo neurologico de consulta, y de la complejidad diagnostica y terapeutica de algunos pacientes, el numero de consultas monograficas de cefalea (CC) y de unidades de cefalea (UC) es muy reducido en nuestro pais. En este articulo pasaremos revista a los principales argumentos que nos permitan, como neurologos, defender la necesidad de la implementacion de una CC/UC, dependiendo de la poblacion que se debe atender, en todos nuestros servicios de neurologia. Para ello deberemos, en primer lugar, vencer las reticencias internas, que hacen que la cefalea sea aun poco apreciada y atractiva dentro de nuestra especialidad. El hecho de que la cefalea justifique mas de un cuarto de las consultas a un servicio de neurologia estandar de nuestro pais y de que existan mas de 200 cefaleas diferentes, algunas de ellas realmente invalidantes, y las nuevas opciones de tratamiento para pacientes cronicos, como la OnabotulinumtoxinA para la migraña cronica o las tecnicas de neuromodulacion, obligan a introducir dentro de nuestras carteras de servicios la asistencia especializada en cefaleas. Aunque no disponemos de datos incontrovertibles, existen ya datos suficientes en la literatura que indican que esta atencion es eficiente en pacientes con cefaleas cronicas no solo en terminos de salud, sino tambien desde el punto de vista economico.

Botulinum toxin A for treating spasticity in adults: costly for French hospitals?

INTRODUCTION: Intramuscular injection of botulinum toxin (BoNTA) is one of the primary treatments for focal spasticity. This treatment is considered costly and the level of reimbursement by health insurance has been decreasing in many countries for several years. The aim of this study was to determine the real cost of treating spasticity with BoNTA and to compare this with the level of reimbursement by the national health insurance in France in 2008 and with a new fee, specific to the injection of BoNTA in ambulatory services. METHOD: A single-center, retrospective study using the 2008 database from a French secondary-care day-hospital unit (treating spasticity in adults with sequelae of stroke, multiple sclerosis or traumatic brain injuries). The level of reimbursement by the French ministry of health for BoNTA treatment for adults with spasticity constituted the "calculated cost" and corresponded to the hospital's "budget". The "real cost" (incurred by the hospital) included the sum of staffing and material costs as well as the number of toxin vials used. The calculated costs for 2009 and 2013 were based on the levels of reimbursement during those years. The difference between real and calculated cost for 2009 and 2013 was estimated considering that the real cost of 2008 was stable. RESULTS: In 2008, 364 patients received BoNTA, resulting in 870 day-hospital admissions. The calculated cost was 459,056€/year and the real cost was 567,438€/year (equivalent to 4.27€/day/patient). The total budget deficit (hospital income minus hospital costs) was 108,383€. The deficit was estimated at 222,892€ in 2009 and 241,188€ in 2013. CONCLUSION: The daily cost of BoNTA treatment for spasticity is reasonable; however, because of the level of reimbursement by the national health insurance in France, the treatment is costly for French hospitals.

Cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia.

PURPOSE: A cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia (CD) was conducted. METHODS: A cost-utility analysis of botulinum toxin type A products was conducted from the U.S. government perspective using a decision-analysis model with a one-year time horizon. Probabilities of the model were taken from several studies using the three botulinum type A products approved by the Food and Drug Administration for the treatment of CD: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). The main outcome measurement was successful treatment response with botulinum toxin type A, measured in quality-adjusted life years (QALYs). Response was defined as a patient who experienced improvement of CD symptoms without a severe adverse event. Probabilistic sensitivity analysis was conducted to test robustness of the base-case results. RESULTS: All three botulinum toxin type A agents were cost-effective at a willingness-to-pay threshold of $100,000 per QALY. Xeomin was the most cost-effective with a cost-effectiveness ratio of $27,548 per QALY. Xeomin was dominant over the alternative agents with equivalent efficacy outcomes and lower costs. Dysport had the second lowest cost-effectiveness ratio ($36,678), followed by Botox ($49,337). The probabilistic sensitivity analysis supported the results of the base-case analysis. Dysport was associated with the lowest wastage (2.2%), followed by Xeomin (10%) and Botox (22.9%). CONCLUSION: A cost-utility analysis found that Xeomin was the more cost-effective botulinum toxin type A product compared with Botox and Dysport for the treatment of CD. Wastage associated with the respective products may have a large effect on the cost-effectiveness of the agents.

Sacral neuromodulation and Botulinum toxin A for refractory idiopathic overactive bladder: a cost-utility analysis in the perspective of Italian Healthcare System.

OBJECTIVES: To assess the relative cost-effectiveness of two therapeutic strategies: one starting with sacral neuromodulation (SNM) versus one starting with Botulinum toxin A (BTX-A) for the management of refractory incontinent idiopathic overactive bladder (OAB) patients, from the perspective of the Italian National Health Service (INHS). METHODS: Direct medical costs (2011) and benefits (quality-adjusted life years-QALYs) were assessed over a ten-year time frame adapting to the Italian practice a published Markov model. Clinical inputs were based on the published literature and on the expert opinion. Resource consumption rates were provided by clinical experts; unit costs were collected from a single hospital accounting and from standard tariff lists and public prices. Interventional procedures and management of adverse events were costed through a micro-costing approach. The primary outcome was incremental costs per QALYs gained (i.e. differential costs divided by differential benefits). Deterministic (DSA) and probabilistic (PSA) sensitivity analyses were conducted to assess the robustness of the model. RESULTS: Starting with SNM appears to be cost effective (i.e. under 40.000/QALY) from year three (21,259/QALY) onwards and becomes dominant (i.e. more effective and less costly) at year ten: cumulative costs were 32,975 for early SNM and 33,309 for early BTX-A, while cumulative QALYs were 7.52 and 6.93, respectively. At year ten, DSA suggests the results robustness and 99.8 % of the PSA iterations fell within the cost-effectiveness threshold. CONCLUSIONS: A therapeutic strategy starting with SNM may be considered cost effective in the midterm and cost saving in the long-term treatment of idiopathic OAB from the INHS perspective.

Cost-effectiveness of novel therapies for overactive bladder.

Overactive bladder is a difficult to treat condition affecting a large proportion of adults resulting in considerable economic impact to society. First-line treatments such as behavioral therapy or antimuscarinic medication are frequently not effective in adequately controlling symptoms or have intolerable side effects. Patients subsequently require second-line therapy including, sacral neuromodulation through either posterior tibial nerve stimulation or sacral nerve stimulation or intra-detrusor injection of Onabotulinumtoxin-A. Mirabegron, a relatively new drug in a separate class, is also employed in the treatment of overactive bladder. The question of which novel therapy to initiate depends on several factors including patient preference, effectiveness and cost. The purpose of this review is to present and discuss the most recent studies pertaining to the cost-effectiveness of novel therapies for overactive bladder.

Cost-effectiveness of sacral neuromodulation compared to botulinum neurotoxin a or continued medical management in refractory overactive bladder.

OBJECTIVES: This study assessed the cost-effectiveness and health-care budget impact of sacral neuromodulation (SNM) in refractory idiopathic OAB-wet patients in Spain. METHODS: A 10-year Markov analytic model was developed to estimate quality-adjusted life-years (QALYs) gained and incontinence episode avoided associated with SNM therapy compared with botulinum neurotoxin A (BoNT-A) or continued optimized medical treatment (OMT). RESULTS: At 10 years, the cumulative costs of SNM, BoNT-A, and OMT were €29,166, €29,458, and €29,370, respectively, whereas the QALYs for SNM, BoNT-A, and OMT are 6.89, 6.38, and 5.12, respectively. Consequently, incremental cost-effectiveness ratios (ICERs) for SNM demonstrate that although the initial costs for SNM are higher than those for the other treatments, decreasing follow-up costs coupled with consistently greater effectiveness in the long term make SNM the economically dominant option at 10 years. Sensitivity analyses suggest that 99.7% and 99.9% (for SNM vs. BoNT-A and OMT, respectively) of the 1000 Monte Carlo iterations fall within the €30,000 cost-effectiveness threshold, considered to be acceptable in Spain. The 10-year incremental cost per incontinence episode avoided for SNM also makes this therapy the dominant option compared to BoNT-A or OMT. Additionally, the estimated budget impact of the gradually increased referral for SNM for the management of OAB patients in Spain is small. CONCLUSIONS: As a treatment option for refractory idiopathic OAB, at 10 years, SNM provides a considerable possibility of symptom and quality-of-life improvement and is cost-effective compared to BoNT-A or continued OMT.

Cost-effectiveness analysis of sacral neuromodulation and botulinum toxin A treatment for patients with idiopathic overactive bladder.

UNLABELLED: Study Type - Therapy (economic analysis). LEVEL OF EVIDENCE: 1b. OBJECTIVE: To assess and compare the costs and effects value of either starting with sacral neuromodulation (SNM) or botulinum toxin A (BTX) treatment in patients with refractory idiopathic overactive bladder from a societal perspective. MATERIALS AND METHODS: An economic model comparing SNM with BTX was developed. A clinical relevant effect (i.e. success) was defined as 50% or greater reduction in incontinence episodes or urgency frequency symptoms. Information on the clinical effectiveness of the two treatments and on the course of the disease with the two treatments were based primarily on published literature and, when required, on expert opinion. Both treatments were assumed to be performed under general anaesthesia and, for SNM treatment, first-stage tined lead test was used. All costs were based on national data from the year 2008. Analyses from the societal perspective were conducted for a 5-year duration. Costs were discounted at 4% and effects at 1.5%. In addition, different modelling scenarios were used to see determine any changes in the results obtained. RESULTS: Starting with SNM resulted in a higher quality adjusted life year (QALY) gain (difference of 0.23) and a higher cost (difference of €6428) compared to starting with BTX. The corresponding incremental cost-effectiveness ratio was €27,991/QALY. The probability of this ratio being cost effective (e.g. under €40,000/QALY) is 88%. SNM starts to be cost-effective after 4 years. SNM was not cost-effective in some other scenarios, such as when BTX was conducted under local anaesthesia or when peripheral nerve evaluation or bilateral testing was used for SNM. CONCLUSIONS: Starting with SNM, treatment is cost-effective after 5 years compared to BTX. However, in some scenarios, such as the use of local anaesthesia for BTX treatment and SNM peripheral nerve evaluation or bilateral test, SNM was not cost-effective.

BoTULS: a multicentre randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A.

OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A plus an upper limb therapy programme with the upper limb therapy programme alone. DESIGN: A multicentre open-label parallel-group randomised controlled trial and economic evaluation. SETTING: Twelve stroke services in the north of England, UK. PARTICIPANTS: Three hundred and thirty-three adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. INTERVENTIONS: The intervention group received botulinum toxin type A injection(s) plus a 4-week programme of upper limb therapy. The control group received the upper limb therapy programme alone. Participants were clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A injection(s) and/or therapy. MAIN OUTCOME MEASURES: The primary outcome was upper limb function 1 month after study entry measured by the Action Research Arm Test (ARAT). A successful outcome was defined as: (1) a change of three or more points on the ARAT scale for a participant whose baseline ARAT score was between 0 and 3, (2) a change of six or more points on the ARAT scale for a participant whose baseline ARAT score was between 4 and 51, or (3) a final ARAT score of 57 for a participant whose baseline ARAT score was 52-56. Outcome assessments were undertaken at 1, 3 and 12 months by an assessor who was blinded to the study group allocation. Upper limb impairment and activity limitation were assessed by: Modified Ashworth Scale; Motricity Index; grip strength; ARAT; Nine-Hole Peg Test; upper limb basic functional activity questions and the Barthel Activities of Daily Living (ADL) Index. Stroke-related quality of life/participation restriction was measured using the Stroke Impact Scale, European Quality of Life-5 Dimensions (EQ-5D) and the Oxford Handicap Scale. Upper limb pain was assessed using numerical rating scales. Participant-selected upper limb goal achievement (1 month only) was measured using the Canadian Occupational Performance Measure. Adverse events were compared. Health-care and social services resource use was compared during the first 3 months postrandomisation. EQ-5D data were used to calculate the quality-adjusted life-years (QALYs) associated with intervention and control treatments, and the incremental cost per QALY gained of botulinum toxin type A plus therapy compared with therapy alone was estimated. The sensitivity of the base-case results to alternative assumptions was investigated, and cost-effectiveness acceptability curves, which summarise the evidence of botulinum toxin type A plus therapy being cost-effective for a range of societal willingness to pay for a QALY values, are presented. RESULTS: Randomisation groups were well matched at baseline. There was no significant difference between the groups for the primary outcome of improved arm function at 1 month. This was achieved by 30/154 (19.5%) in the control group and 42/167 (25.1%) in the intervention group (p = 0.232). The relative risk of having a 'successful treatment' in the intervention group compared with the control group was 1.3 [95% confidence interval (CI) 0.9 to 2.0]. No significant differences in improved arm function were seen at 3 or 12 months. In terms of secondary outcomes, muscle tone/spasticity at the elbow was decreased in the intervention group compared with the control group at 1 month. The median change in the Modified Ashworth Scale was - 1 in the intervention group compared with zero in the control group (p < 0.001). No difference in spasticity was seen at 3 or 12 months. Participants treated with botulinum toxin type A showed improvement in upper limb muscle strength at 3 months. The mean change in strength from baseline (upper limb component of the Motricity Index) was 3.5 (95% CI 0.1 to 6.8) points greater in the intervention group compared with the control group. No differences were seen at 1 or 12 months. Participants in the intervention group were more likely to be able to undertake specific basic functional activities, e.g. dress a sleeve, clean the palm and open the hand for cutting fingernails. At 1 month, 109/144 (75.7%) of the intervention group and 79/125 (63.2%) of the control group had improved by at least one point on a five-point Likert scale for at least one of these tasks (p = 0.033). At 3 months the corresponding proportions were 102/142 (71.8%) of the intervention group and 71/122 (58.2%) of the control group (p = 0.027). Improvement was sustained at 12 months for opening the hand for cleaning the palm and opening the hand for cutting the nails but not for other activities. Pain rating improved by two points on a 10-point severity rating scale in the intervention group compared with zero points in the control group (p = 0.004) at 12 months, but no significant differences were seen at 1 or 3 months. There were a number of occasions when there were statistically significant differences in favour of the intervention group; however, these differences were small and of uncertain clinical relevance. These differences were: 3 months - upper limb function (change in ARAT score from baseline), pain (EQ-5D) and participation restriction (Oxford Handicap Scale); 12 months - anxiety/depression (EQ-5D) and participation restriction (Oxford Handicap Scale). No differences in grip strength, dexterity or the Barthel ADL Index were found at any time point. There were no differences between the groups for achievement of patient-selected goals. There was a higher incidence of general malaise/flu-like/cold symptoms in participants treated with botulinum toxin type A with a relative risk of 7.6 (95% CI 1.8 to 32.3). Only one serious adverse event (dysphagia) was potentially related to botulinum toxin type A. Time since stroke and severity of initial upper limb function were preplanned subgroup analyses. There was no significant difference in either subgroup for achievement of ARAT 'success' following treatment with botulinum toxin type A. The base-case incremental cost-effectiveness ratio was 93,500 pounds per QALY gained and estimation of the cost-effectiveness acceptability curve for botulinum toxin type A plus the upper limb therapy programme indicated that there was only a 0.36 probability of it being cost-effective at a threshold ceiling ratio of 20,000 pounds per QALY. CONCLUSIONS: The addition of botulinum toxin type A to an upper limb therapy programme to treat spasticity due to stroke did not enhance improvement in upper limb function when assessed by the prespecified primary outcome measure at 1 month. However, improvements were seen in muscle tone at 1 month, upper limb strength at 3 months, upper limb functional activities related to undertaking specific basic functional tasks at 1, 3 and 12 months, and upper limb pain at 12 months. Botulinum toxin was well tolerated and side effects were minor. The addition of botulinum toxin type A to an upper limb therapy programme for the treatment of upper limb spasticity due to stroke was not estimated to be cost-effective at levels of willingness to pay for a QALY set by NHS decision-makers. TRIAL REGISTRATION: ISRCTN78533119; EudraCT 2004-002427-40; CTA 17136/0230/001.

Cost analysis of interventions for antimuscarinic refractory patients with overactive bladder.

OBJECTIVES: To estimate average, initial, and cumulative procedure related costs from a US payer perspective extending up to 3 years for the overactive bladder (OAB) interventions: sacral neuromodulation (SNM), intra-detrusor botulinum toxin A (BoNTA), and augmentation cystoplasty (AC) for antimuscarinic refractory patients. METHODS: Costs (2007 US dollars) were calculated using Current Procedural Terminology (CPT) codes, Ambulatory Payment Classification (APC) codes; Diagnosis Related Group (DRG) payments, and Healthcare Common Procedure Coding System (HCPCS) Level II Codes extracted from the literature and from the SNM device manufacturer. CPT codes were converted to costs using the Center for Medicare and Medicaid Services (CMS) Relative Value Unit (RVU) fee schedule. Sensitivity analyses were performed to evaluate assumptions and uncertainty of results based on plausible variation in estimates of key cost drivers. RESULTS: The initial treatment cost was $22,226, $1,313, and $10,252 for SNM, intra-detrusor injection of BoNTA, and AC respectively. The first-year cost was $23,614, $2626, and $11,637 respectively. Three years after initiating treatment, the cumulative cost was $26,269, $7651, and $14,337 respectively. Sensitivity analyses revealed that SNM persisted as the most costly intervention in all scenarios. The 3-year cumulative cost range produced by the sensitivity analyses for SNM, BoNTA, and AC was $25,384-$27,357, $4586-$11,476, and $12,315-$16,830, respectively. CONCLUSIONS: All estimates of cost endpoints for SNM were greater than those for BoNTA and AC. These cost estimates, when combined with data on outcomes and risks, are important components of a robust health care technology assessment of antimuscarinic treatment failure options.

Cost-effectiveness of sacral neuromodulation versus intravesical botulinum A toxin for treatment of refractory urge incontinence.

PURPOSE: We determined the cost-effectiveness of sacral neuromodulation vs intravesical botulinum toxin A for the treatment of refractory urge incontinence. MATERIALS AND METHODS: We developed a Markov decision model using a societal perspective to compare costs (2008 U.S. dollars) and effectiveness (quality adjusted life-years) of sacral nerve stimulation and botulinum toxin A. Our primary outcome was the incremental cost-effectiveness ratio, which was defined as (sacral nerve stimulation cost - botulinum toxin A cost)/(sacral nerve stimulation quality adjusted life-year - botulinum toxin A quality adjusted life-year). Sensitivity analyses were performed to assess the impact of varying efficacy, costs and adverse event rates over the range of reported values. RESULTS: In the base case scenario sacral nerve stimulation was more expensive ($15,743 vs $4,392) and more effective (1.73 vs 1.63 quality adjusted life-years) than botulinum toxin A during a 2-year period. The incremental cost-effectiveness ratio was $116,427 per quality adjusted life-year. Using conventional incremental cost-effectiveness ratio thresholds of $50,000 and $100,000 per quality adjusted life-year, sacral nerve stimulation was not cost-effective. In sensitivity analyses intravesical botulinum generally remained cost-effective. CONCLUSIONS: During a 2-year period botulinum toxin A was cost-effective compared to sacral neuromodulation for the treatment of refractory urge incontinence. Additional data regarding time to failure after botulinum toxin A injections, long-term efficacy with repeat botulinum toxin A injections and long-term complications with both therapies will be helpful for future cost-effectiveness studies.

Humanistic, utilization, and cost outcomes associated with the use of botulinum toxin for treatment of refractory migraine headaches in a managed care organization.

BACKGROUND: Few patients with migraine syndrome receive treatment with preventive medication regimens, and some of these patients fail to gain adequate migraine relief. Botulinum toxin has been suggested to be effective in the treatment of migraine for a select population. An integrated health system created a medical policy and a supporting preauthorization form that permits coverage of botulinum toxin for the off-label treatment of migraine for patients who (1) fail at least 3 drug classes for acute treatment, (2) fail at least 4 different preventive medication classes, and (3) receive consultation from a neurologist. OBJECTIVES: To (1) evaluate the impact of botulinum toxin therapy on quality-of-life (QOL) measures evaluated by direct member survey results, and (2) assess the use and cost of migraine-related medications and overall medical and pharmacy services pre- and post-botulinum toxin therapy. METHODS: The study was a retrospective analysis of administrative claims data from a 500,000-member integrated health system for the time period January 1, 2003, to October 31, 2007. Administrative claims data were used to identify members with a billing code (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]) for migraine (346.xx), tension headache (307.81), or headache (784.0) diagnosed by a neurologist. Administrative claims data for these patients were then queried for the use of botulinum toxin for dates of service from January 1, 2003, through October 31, 2006. A survey was sent to the identified patients (N=54) to assess 6 QOL measures associated with the use of botulinum toxin. Self-reported symptomatic improvement was assessed using a 5-point Likert scale for 6 questions regarding headache severity, headache frequency, use of rescue medications, productivity/absenteeism, recreational activities, and life enjoyment. For the subset of patients (n = 32) who maintained health plan eligibility from 18 months before through 18 months after the first botulinum toxin therapy claim (index date), medical and pharmacy claims data were used to assess the utilization and cost of specific medications and overall pharmacy and medical costs for the 18-month pre-index and post-index periods. Cost was defined as allowed charge, which is the sum of plan cost and member cost. RESULTS: Of 54 surveys sent to all patients identified as having used botulinum toxin for the treatment of migraine from January 1, 2003, to October 31, 2006, 34 surveys were returned (63%). Almost 3 of 4 respondents (73%) reported moderate or better improvement in overall migraine or headache QOL measures, and 27% reported little or no improvement. For the 32 patients with continuous eligibility for the total observation period of 36 months, the average migraine-related pharmacy utilization, excluding botulinum toxin, increased by 50.5%, from 1.84 claims per patient per month (PPPM) in the 18-month pre-index period to 2.77 claims PPPM in the 18-month post-index period (P = 0.011) and by 59.5% by mean days supply (42.58 days to 67.93, P=0.008). Total migraine-related pharmacy cost increased by 80.9%, from $142.08 PPPM to $256.97 PPPM (P=0.013). Acute-treatment migraine-related pharmacy utilization increased from 1.23 claims PPPM to 1.92 claims PPPM (P=0.004). There was no significant change in either the number of claims for migraine prophylaxis medications (0.61 PPPM to 0.85 PPPM, P=0.121) or the use of hospital emergency room services related to migraine or headache (0.07 PPPM vs. 0.10 PPPM, P=0.449). The mean migraine-related and nonmigraine-related (i.e., all-cause) combined medical/hospital and pharmacy expense, including botulinum toxin, increased by 111.3%, from $651.13 PPPM in the pre-index period to $1,376.05 PPPM in the post-index period (P<0.001). CONCLUSION: The majority of patients who received botulinum toxin for refractory migraine reported improvement in disease-specific symptoms and overall QOL, but total medical and pharmacy costs were higher in the period after treatment, and there was no reduction in the use of other migraine-related medications.

Botulinum toxin A versus bupivacaine trigger point injections for the treatment of myofascial pain syndrome: a randomised double blind crossover study.

The treatment of myofascial pain syndrome (MPS) is diverse and includes trigger point injections of various substances including local anesthetics, steroids and Botulinum toxin A (BTX A). The purpose of this study was to compare the effectiveness of trigger point injections using BTX A versus bupivacaine, both in combination with a home-based rehabilitation program. To be enrolled, subjects first had to demonstrate responsiveness to bupivacaine trigger point injection. In this single center, double blind, randomized, cross-over trial, 18 patients with MPS received trigger point injections of either 25 units Botulinum toxin A or 0.5 ml of 0.5% bupivacaine per trigger point. A maximum of eight trigger points were injected per subject. Subjects were followed until their pain returned to 75% or more of their pre-injection pain for two consecutive weeks, after which there was a 2 week wash-out period. The subjects then crossed over and had the same trigger points injected with the other agent. All subjects participated in a home exercise program involving static stretches of the affected muscles. Both treatments were effective in reducing pain when compared to baseline (P=0.0067). There was, however, no significant difference between the BTX A and 0.5% bupivacaine groups in duration or magnitude of pain relief, function, satisfaction or cost of care (cost of injectate excluded). Considering the high cost of BTX A, bupivacaine is deemed a more cost-effective injectate for MPS.