Economic analysis of Electrical Muscle Stimulator with Multipath technology for the treatment of stress urinary incontinence: a UK-based cost-utility analysis.

Background: Stress urinary incontinence (SUI) is a debilitating and highly prevalent condition in the UK. The condition is associated with a significant economic burden for affected patients and society. Current treatment options for SUI include minimally invasive therapies, medication and surgical intervention for the most serious cases. Electrical Muscle Stimulator with Multipath technology is a recently developed device for the treatment of SUI that relies on neuromuscular external electrical stimulation (NEES) technology. The clinical efficacy of the device has been proven in previous studies, but existing evidence surrounding its economic viability is limited.Objectives: To assess the cost-utility of the Electrical Muscle Stimulator with Multipath technology Therapy device for the treatment of SUI amongst women in a UK setting.Methods: An economic model was developed to consider the cost-utility (cost per quality-adjusted life-year [QALY] gained) of Electrical Muscle Stimulator with Multipath technology compared with current practice. A Markov model was developed, with costs and health effects estimated over the lifetime of the patient in the base-case analysis. The model was developed to reflect the treatment pathways typically followed by patients with SUI in the UK. Parameter uncertainty was explored in deterministic and probabilistic sensitivity analyses.Results: Base-case results indicate that Electrical Muscle Stimulator with Multipath technology results in cost savings and QALY gains over the patient's lifetime. In the "cure" analysis, the intervention is £250 less costly and leads to a 0.03 QALY gain per patient, while in the "improvement analysis", the intervention is £327 less costly and leads to a 0.13 QALY gain per patient. Results from the probabilistic sensitivity analyses show that the likelihood of Electrical Muscle Stimulator with Multipath technology being cost-effective is greater than 74% across all willingness-to-pay thresholds in the two analyses presented.Conclusions: Electrical Muscle Stimulator with Multipath technology is a potentially cost-effective treatment option for patients with SUI who have failed first-line treatment. It could reduce costs to the health care service and improve quality-of-life for selected patients over their lifetime.

MORPHOLOGICAL ASSESSMENT OF NO-SYNTHASE DISTRIBUTION IN OVERACTIVE BLADDER AND STRESS URINE INCONTINENCE IN ANIMAL MODELS ADMINISTERED WITH EXPERIMENTAL PHARMACOCORRECTION REGIMENS.

The objective of the study was immunohistochemical evaluation of distribution of various NO synthase fractions in the structural elements of the bladder wall under stress urinary incontinence and its overactivity prior and post Mirabegron, Spasmex, Quercetin therapies and their combinations with Testosterone and Estradiol. Using the immunohistochemical method, we studied the expression of the main fractions of NO synthase in experimental models of hyperactive bladder (OAB) and stress urinary incontinence (SUI). We found that OAB and SUI were characterized by emergence of expression of the inducible fraction (iNOS) predominantly in the interstitial cells of the muscular layer of the bladder and reduced expression of endothelial (eNOS) and neuronal (nNOs) NO synthase fractions. In contrast to Spasmex, Mirabegron and Quercetin in combination with Testosterone and Estradiol contributed to stabilization of eNOS and nNOs expression already at early observation phases, and reduced the level of iNOS expression with its further disappearance in the later observation period.

Traditional suburethral sling operations for urinary incontinence in women.

BACKGROUND: Stress urinary incontinence constitutes a significant health and economic burden to society. Traditional suburethral slings are one of the surgical operations used to treat women with symptoms of stress urinary incontinence. OBJECTIVES: To determine the effects of traditional suburethral slings on stress or mixed incontinence in comparison with other management options. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register (searched 3 June 2010) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised trials that included traditional suburethral slings for the treatment of stress or mixed urinary incontinence. DATA COLLECTION AND ANALYSIS: At least three reviewers independently extracted data from included trials onto a standard form and assessed trial methodological quality. The data abstracted were relevant to predetermined outcome measures. Where appropriate, we calculated a summary statistic: a relative risk for dichotomous data and a weighted mean difference for continuous data. MAIN RESULTS: We included 26 trials involving 2284 women. The quality of evidence was moderate for most trials and there was generally short follow-up ranging from 6 to 24 months.One medium-sized trial compared traditional suburethral sling operations with oxybutynin in the treatment of women with mixed urinary incontinence. Surgery appeared to be more effective than drugs in treating participant-reported incontinence (n = 75, risk ratio (RR) 0.18, 95% confidence interval (CI) 0.08 to 0.43).One trial found that traditional slings were more effective than transurethral injectable treatment (RR for clinician-assessed incontinence within a year 0.21, 95% CI 0.09 to 0.21)Seven trials compared slings with open abdominal retropubic colposuspension. Participant-reported incontinence was lower with the slings after one year (RR 0.75, 95% CI 0.62 to 0.90), but not when assessed by clinicians. Colposuspension, however, was associated with fewer peri-operative complications, shorter duration of use of indwelling catheter and less long-term voiding dysfunction. One study showed there was a 20% lower risk of bladder perforation with the sling procedure but a 50% increase in urinary tract infection with the sling procedure compared with colposuspension. Fewer women developed prolapse after slings (compared with after colposuspension) in two small trials but this did not reach statistical significance.Twelve trials addressed the comparison between traditional sling operations and minimally invasive sling operations. These seemed to be equally effective in the short term (RR for incontinence within first year 0.97, 95% CI 0.78 to 1.20) but minimally invasive slings had a shorter operating time, fewer peri-operative complications (other than bladder perforation) and some evidence of less post-operative voiding dysfunction and detrusor symptoms.Six trials compared one type of traditional sling with another. Materials included porcine dermis, lyophilised dura mater, fascia lata, vaginal wall, autologous dermis and rectus fascia. Participant-reported improvement rates within the first year favoured the traditional autologous material rectus fascia over other biological materials (RR 0.45, 95% CI 0.21 to 0.98). There were more complications with the use of non-absorbable Gore-Tex in one trial.Data for comparison of bladder neck needle suspension with suburethral slings were inconclusive because they came from a single trial with a small specialised population.No trials compared traditional suburethral slings with anterior repair, laparoscopic retropubic colposuspension or artificial sphincters. Most trials did not distinguish between women having surgery for primary or recurrent incontinence when reporting participant characteristics.For most of the comparisons, clinically important differences could not be ruled out. AUTHORS' CONCLUSIONS: Traditional slings seem to be as effective as minimally invasive slings, but had higher rates of adverse effects. This should be interpreted with some caution however, as the quality of evidence for the studies was variable, follow-up short and populations small, particularly for identifying complication rates. Tradional sling procedures appeared to confer a similar cure rate in comparison to open retropubic colposuspension, but the long-term adverse event profile is still unclear. A brief economic commentary (BEC) identified two studies suggesting that traditional slings may be more cost-effective compared with collagen injection but not cost-effective when compared with minimally invasive sling operations. Reliable evidence to clarify whether or not traditional suburethral slings may be better or worse than other surgical or conservative management options is lacking.

Cost utility analysis of urethral bulking agents versus midurethral sling in stress urinary incontinence.

OBJECTIVE: The aim of this study was to determine the cost utility of urethral bulking agents (BA) compared with midurethral slings (MUS) in the treatment of stress urinary incontinence (SUI) in patients without urethral hypermobility. METHODS: A decision tree was constructed to compare the cost utility of urethral BA versus MUS in the setting of SUI without urethral hypermobility. Probability estimates for success, failure, and complications were obtained from the published literature. Immediate-term, short-term, and longer-term complications were accounted for over a 1-year time horizon in the model. One-way and 2-way sensitivity analyses and Monte Carlo simulations were performed to assess the robustness of our results. RESULTS: Our model demonstrated that MUS cost $436,465 more than BA for every 100 women treated in 1 year. Using MUS compared with BA leads to an incremental cost-effectiveness ratio of $70,400 per utility gained. Assuming a willingness to pay of $50,000, this makes MUS not cost-effective as a first-line treatment in many situations. When MUS costs less than $5132, it becomes a cost-effective first-line treatment, and when it costs less than $2035, it is cost saving. CONCLUSIONS: Bulking agents are more cost-effective than MUS over a 1-year time horizon in the treatment of SUI in patients without urethral hypermobility. In women who lack urethral hypermobility, BA remain a cost-effective option in this patient population.

Urinary incontinence: pharmacotherapy options.

The impact of incontinence is felt by millions of people worldwide, with tremendous decrement in quality of life and enormous cost reaching billions of dollars. Urinary incontinence is defined as 'involuntary leakage of urine' and is categorized into two main types: urgency urinary incontinence (UUI) and stress urinary incontinence (SUI). Behavioral modifications and pharmacologic therapies, primarily antimuscarinic agents, are the mainstay of treatment for UUI. These drugs are moderately efficacious but have troublesome side-effects, the combination resulting in poor compliance and persistence with therapy. There are several agents on the market today, each with some variation in pharmacologic properties. Whether these translate into meaningful differences in clinical efficacy and tolerability remains a matter of debate. Treatment of SUI has seen little success with pharmacologic therapy. In Europe, duloxetine is approved for treatment of SUI with marginal success rates; this drug, although available in the United States for treatment of depression, is not approved for SUI. The search for newer and better pharmacologic options and novel therapies is on-going, fueled primarily by the high prevalence of bothersome incontinence and the tremendous number of health care dollars spent on current therapy. This review addresses pharmacologic options for treatment of urinary incontinence.

Cost-effectiveness of duloxetine: the Stress Urinary Incontinence Treatment (SUIT) study.

OBJECTIVE: To assess the cost-effectiveness of duloxetine compared with conservative therapy in women with stress urinary incontinence (SUI). METHODS: Cost and outcome data were taken from the Stress Urinary Incontinence Treatment (SUIT) study, a 12-month, prospective, observational, naturalistic, multicenter, multicountry study. Costs were assessed in UK pound and outcomes in quality adjusted life years using responses to the EuroQol (EQ-5D); numbers of urine leaks were also estimated. Potential selection bias was countered using multivariate regression and propensity score analysis. RESULTS: Duloxetine alone, duloxetine in combination with conservative treatment, and conservative treatment alone were associated with roughly two fewer leaks per week compared with no treatment. Duloxetine alone and with conservative treatment for SUI were associated with incremental quality-adjusted life-years (QALYs) of about 0.03 over a year compared with no treatment or with conservative treatment alone. Conservative treatment alone did not show an effect on QALYs. None of the interventions appeared to have marked impacts on costs over a year. Depending on the form of matching, duloxetine either dominated or had an incremental cost-effectiveness ratio (ICER) below pound900 per QALY gained compared with no treatment and with conservative treatment alone. Duloxetine plus conservative therapy had an ICER below pound5500 compared with no treatment or conservative treatment alone. Duloxetine compared with duloxetine plus conservative therapy showed similar outcomes but an additional cost for the combined intervention. CONCLUSIONS: Although the limitations of the use of SUIT's observational data for this purpose need to be acknowledged, the study suggests that initiating duloxetine therapy in SUI is a cost-effective treatment alternative.

Is there a place for duloxetine?

Duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, is licensed in the UK under two brand names for a total of three different indications. It is available as Cymbalta (jointly promoted by Boehringer Ingelheim and Lilly) for the treatment of patients with major depression, or with diabetic peripheral neuropathic pain; and as Yentreve (Lilly) for the treatment of women with "moderate to severe" stress urinary incontinence. Here we consider whether duloxetine has a role in the treatment of patients with any of these conditions.

Treatment of stress urinary incontinence with non-animal stabilised hyaluronic acid/dextranomer (NASHA/Dx) gel : An analysis of utility and cost.

BACKGROUND: The Zuidex system is a treatment for stress urinary incontinence comprising four prefilled syringes of non-animal stabilised hyaluronic acid/dextranomer (NASHA/Dx) gel and the Implacer device. This study aimed to investigate utility (patients' preferences for given health states) with NASHA/Dx gel therapy and to compare resource utilisation of NASHA/Dx gel treatment with tension-free vaginal tape (TVT). METHODS: Utility was measured using EuroQol (EQ-5D), a generic utility instrument. For the cost of NASHA/Dx gel treatment, data were collected prospectively from participants in a 12-month efficacy study (n = 82). Retrospective analysis of a comparable group of patients (n = 77; 3-6 months' follow-up) was used to obtain equivalent costs for TVT. Costs were analysed for both Sweden and France. RESULTS: NASHA/Dx gel produced a utility gain of 0.048 at 3 months and 0.014 at 12 months. The estimated mean total 3-month cost per patient with NASHA/Dx gel was euro 2412 in Sweden and euro 2005 in France. The corresponding values for 12 months, including 14% of patients undergoing TVT, were euro 3370-euro 3417 and euro 2935-euro 2976 for Sweden and France, respectively. In comparison, the total costs of treatment with TVT over 3-6 months were euro 3169-euro 3504 and euro 5181-euro 5471 for Sweden and France, respectively. CONCLUSIONS: NASHA/Dx gel provides utility benefits that are similar to those previously reported for TVT and, depending on the country in which the treatment is performed, are associated with similar or lower overall costs in the short to medium term. From an economic perspective, NASHA/Dx gel could be considered at least as favourable as TVT, pending the availability of long-term effectiveness data.

Injectables for the treatment of stress urinary incontinence: current use and future perspectives.

Stress urinary incontinence is a prevalent symptom among women. It also affects men, primarily those operated on for prostate disease. Even though it is not life threatening, it seriously impacts quality of life. Bulking agents have been used in the treatment of incontinence for many decades, offering a treatment option for both women and men. Their short-term efficacy is satisfactory, but there is concern regarding durability of effect. Despite concerns regarding efficacy, the minimally invasive nature of the technique, with uncommon and self-limited complications, has made injectables quite popular among both physicians and patients. In light of recent developments in the surgical treatment of incontinence, resulting in highly efficacious, but also easy and safe-to-perform, procedures, the role of injectables must be re-evaluated. In these cost-conscious times, health economics is also an important issue, and comparative cost-effectiveness assessment of available treatment options is becoming imperative.

The direct cost of stress urinary incontinence among women in a Medicaid population.

OBJECTIVE: To describe health care utilization and costs for women diagnosed with stress urinary incontinence in a Medicaid population. STUDY DESIGN: We utilized a pooled database of claims for women enrolled in Medicaid in 1 of 3 states. Health care utilization and costs were compared for 12 months before and 12 months after a woman's urinary incontinence diagnosis. Additional analyses utilized data from a fourth state. RESULTS: Of 13,672 women with diagnosed stress urinary incontinence, average urinary incontinence-related costs were approximately 800 dollars in the 12-month study period, less than 0.1% of total Medicaid spending. Thirteen percent of women underwent a surgery for stress urinary incontinence in the study period, with sling procedures performed most commonly. CONCLUSION: Although population prevalence estimates of any stress urinary incontinence symptoms often are high, diagnosis and health care utilization in the Medicaid population is low. Overall costs of stress urinary incontinence treatment in Medicaid currently are minimal. Further efforts to understand the appropriate detection, diagnosis, and treatment of women with stress urinary incontinence are needed.

Duloxetine: new drug. For stress urinary incontinence: too much risk, too little benefit.

(1) The first-line treatment for women with stress urinary incontinence consists of pelvic floor exercises, which are risk-free and effective in two-thirds to three-quarters of cases. (2) Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the first drug to be marketed in France for the treatment of moderate to severe stress urinary incontinence, after receiving European marketing authorization. (3) A dose-ranging study and three placebo-controlled trials lasting no more than three months showed that duloxetine reduced the frequency of stress incontinence by a median of one episode a day as compared with placebo. The tangible impact of duloxetine on quality of life is doubtful, with a maximum gain of five points on a 100-point scale. (4) A trial lasting 36 weeks showed that duloxetine was no more effective than placebo. (5) One trial compared a combination of physiotherapy and duloxetine versus each treatment alone and placebo. The published report of this trial is restricted to the duloxetine-placebo comparison, which raises doubts as to the possible benefit of the combination of duloxetine and physiotherapy. (6) About one-quarter of patients enrolled in clinical trials stopped taking duloxetine after less than three months because of adverse effects. More than 40 different types of adverse effects have been reported, including suicide attempts and potentially severe hepatic disorders. (7) Duloxetine is metabolised by the cytochrome P450 isoenzymes CYP 1A2 and CYP 2D6, creating a risk of interactions with other drugs that follow these metabolic pathways. (8) In practice, purely symptomatic treatments that have no documented efficacy but many adverse effects should not be used, especially when there is an alternative treatment with a positive risk-benefit balance.

A retrospective claims analysis of the direct costs of stress urinary incontinence.

The aim of this study was to evaluate direct expenditures associated with urinary incontinence and overall medical expenditures incurred by women diagnosed with stress urinary incontinence (SUI). The study design was a retrospective analysis of administrative claims data. We identified women with a diagnosis of SUI and no stress, urge or mixed urinary incontinence in the preceding 12 months using the MarketScan 1996-1999 databases. Total expenditures, as well as urinary incontinence-related expenditures, were summarized during the 12 months before and after the initial SUI diagnosis. We also compared expenditures for SUI patients receiving surgical treatment to expenditures for those who did not. There were 8126 patients who met the eligibility criteria. Total healthcare expenditures in the year prior to the initial SUI diagnosis were approximately half of those in the year following the initial diagnosis ($4478 vs $9147). For the subset of patients treated with surgery there was a threefold increase ($4575 vs $14129) in costs. A sensitivity analysis in patients with no comorbid urinary diagnoses found somewhat lower costs but a similar rate of increase in costs between the pre-period and the study period ($3884 vs $7075). Among women with no comorbid urinary diagnoses, approximately 11% ($769; SD $1180) of total mean regression-adjusted annual expenditures ($6892; SD $5067) was attributable to UI. Predicted total expenditures for surgery patients without comorbid urinary diagnoses were $13 212 (SD $7967), 28% of which ($3640;SD $681) were for UI-related costs. We concluded that after diagnosis, annual expenditures for patients were roughly twice those in the year prior to diagnosis. Multivariate analysis suggests that in the year after SUI diagnosis, UI treatment costs represented approximately 10% of total expenditures for all SUI patients, and 26%-28% of total expenditures for the subset of surgically treated patients.

Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency.

Menopause and the accompanying reduction in estrogen production may cause a number of symptoms in women which include hot flushes, sweating, mood and sleep disturbances, fatigue and urogenital dysfunction. The effectiveness of estrogen-based hormone replacement therapy (HRT) in ameliorating these symptoms, and in preventing long term sequelae such as osteoporosis, is well established. Comparative trials indicate that oral conjugated estrogens 0.625mg, oral ethinyl estradiol 0.02mg and transdermal estradiol 0.05mg have equivalent efficacy in relief of mild to moderate menopausal symptoms and prevention of bone mineral loss. Concomitant progestogen therapy is usually prescribed for women with intact uteri to protect against endometrial hyperplasia and carcinoma. The addition of progestogen maintains and may even enhance the bone-conserving effects of estrogen, and continuous regimens appear to reduce the incidence of irregular menses. Adverse reactions are predominantly local skin irritation with transdermal preparations (14% of patients) and systemic effects common to most forms of HRT including breast tenderness, flushing, headache and irregular bleeding, occurring in less than or equal to 2% of patients. Data concerning the effect of HRT on quality of life are limited, but most analyses have assigned utility values of 0.99 for mild and 0.95 for severe menopausal symptoms. However, recent clinical data suggest that these utility values may underestimate the impact of menopausal symptoms on quality of life. The cost benefit and cost effectiveness of HRT in the treatment of menopausal symptoms have not been fully researched, although preliminary results suggest that conjugated estrogens and transdermal estradiol compare well with alternative therapies such as veralipride and Chinese medicines. A Swedish study using a prevalence-based approach estimated that estriol treatment in all women with urinary incontinence aged greater than or equal to 65 years resulted in monetary savings compared with treating 20% of women. Cost-utility data indicated that the change in quality-adjusted life years (QALYs) with HRT was always positive, but the degree of change was determined by the baseline assumptions. Estimated changes in QALYs with HRT ranged from 0.006 for 5 years of treatment with unopposed estrogen in women with intact uteri, to 0.5 for 10 years of the same treatment in women with severe menopausal symptoms following hysterectomy. Compliance with HRT is suboptimal as 5 to 50% of women withdraw from therapy, thereby increasing costs per year of life saved.(ABSTRACT TRUNCATED AT 400 WORDS)