S. Aballea

Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison.

CONTEXT Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3-adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms. OBJECTIVE To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 mg versus antimuscarinics in patients with OAB. EVIDENCE ACQUISITION A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision). EVIDENCE SYNTHESIS Overall, 44 RCTs involving 27,309 patients were included. The MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics. CONCLUSIONS Mirabegron 50 mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.

Quality of life is predictive of relapse in schizophrenia

BackgroundThe objective of this study was to evaluate whether quality of life (QoL), as measured by the SF36 and the Quality of Life Interview (QoLI), is predictive of relapse for patients with schizophrenia.MethodsUsing data from a multicenter cohort study conducted in France, Germany, and the United-Kingdom (EuroSC), we performed Cox proportional-hazards models to estimate the associations between QoL at baseline and the occurrence of relapse over a 24-month period, with adjustment for age; gender; positive, negative and general psychopathology PANSS factors; functioning (GAF); medication; side-effects; and compliance measures.ResultsOur sample consisted of 1,024 patients; 540 (53%) had at least one period of relapse, and 484 (47%) had no relapse. QoL levels were the most important features predicting relapse. We found that a higher level of QoL predicts a lower rate of relapse at 24 months: HR = 0.82 (0.74; 0.91), p < 0.001 for the SF36-Physical Composite Score; and HR = 0.88 (0.81; 0.96), p = 0.002 for the SF36-Mental Composite Score. These results were not confirmed using the QoLI: HR = 0.91 (0.81; 1.01), p = 0.083. To a lesser extent, older age, better functioning, and a higher compliance score also predict a lower rate of relapse at 24 months (HRs from 0.97 to 0.98; p < 0.05).ConclusionsQoL, as assessed by the SF36, is an independent predictor of relapse at a 24-month follow-up in schizophrenia. This finding may have implications for future use of the QoL in psychiatry. Moreover, our findings may support the development and monitoring of complementary therapeutic approaches, such as ‘recovery-oriented’ combined with traditional mental health cares to prevent relapse.

A critical literature review of health economic evaluations of rotavirus vaccination

Two licensed vaccines are available to prevent RVGE in infants. A worldwide critical review of economic evaluations of these vaccines was conducted. The objective was to describe differences in methodologies, assumptions and inputs and determine the key factors driving differences in conclusions. 68 economic evaluations were reviewed. RV vaccination was found to be cost-effective in developing countries, while conclusions varied between studies in developed countries. Many studies found that vaccination was likely to be cost-effective under some scenarios, such as lower prices scenarios, inclusion of herd protection, and/or adoption of a societal perspective. Other reasons for variability included uncertainty around healthcare visits incidence and lack of consensus on quality of life (QoL) valuation for infants and caregivers. New evidence on the vaccination effectiveness in real-world, new ways of modeling herd protection and assessments of QoL in children could help more precisely define the conditions under which RV vaccination would be cost-effective in developed countries.

Analyse coût-efficacité d’un test prédictif de la chimiothérapie dans le cancer du sein (Oncotype DX®) en France

BACKGROUND In breast cancer, adjuvant chemotherapy is often prescribed as a precautionary measure and sometimes unnecessarily. A diagnostic test based on estimating the risk of recurrence at 10 years for women with breast cancer in early stage has been developed (Oncotype DX(®)). METHOD A Markovs model was adapted to evaluate the long-term effect of this test in terms of costs and life-years gained in French clinical practice for patients with ER+, HER2-, node-negative early-stage breast cancer. Input data were obtained from an international meta-analysis evaluating the proportions of patients in which the genetic test led to changes in the oncologists decision. Costs and epidemiological data were specific to France. The analysis was conducted in accordance with methodological recommendations from the Haute Autorité de santé. RESULTS The test is associated with net cost savings of €570 per patient (€1,600 with productivity loss) from societal perspective and gains of 0.15 life-years and 0.14 quality-adjusted life-years per patient. CONCLUSIONS The use of the test represents efficient use of health care resources in French practice. This test provides an opportunity to optimize treatment prescription by avoiding unnecessary chemotherapies and by prescribing chemotherapy to women who would not have received it based on standard decision criteria.

Relapse according to antipsychotic treatment in schizophrenic patients: a propensity-adjusted analysis.

ObjectiveTo compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period.MethodsUsing data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy).ResultsOur sample consisted in 183 patients; 50 patients (27.3%) had at least one period of relapse and 133 had no relapse (72.7%). Thirty-eight (37.7) percent of the patients received polypharmacy. The most severely ill patients were given polypharmacy: the age at onset of illness was lower in the polypharmacy group (p = 0.03). Patients that received polypharmacy also presented a higher general psychopathology PANSS subscore (p = 0.04) but no statistically significant difference was found in the PANSS total score or the PANSS positive or negative subscales. These patients were more likely to be given prescriptions for sedative drugs (p < 0.01) and antidepressant medications (p = 0.03). Relapse was found in 23.7% of patients given monotherapy and 33.3% given polypharmacy (p = 0.16). After stratification according to quintiles of the propensity score, which eliminated all significant differences for baseline characteristics, antipsychotic polypharmacy was not statistically associated with an increase of relapse: HR = 1.686 (0.812; 2.505).ConclusionAfter propensity score adjustment, antipsychotic polypharmacy is not statistically associated to an increase of relapse. Future randomised studies are needed to assess the impact of antipsychotic polypharmacy in schizophrenia.

Estimating EQ-5D and OAB-5D health state utilities for patients with overactive bladder

BackgroundLimited utility data on patients suffering from overactive bladder (OAB) are available in the literature. The objectives of this study were to estimate utility values in patients with OAB using the generic EQ-5D questionnaire and the OAB-5D disease specific questionnaire, to investigate the relationship between utilities and symptoms, and to evaluate the sensitivity of the two instruments to changes in symptom severity.MethodsAnalyses were based on pooled data from three large multicenter randomized 12-week placebo-controlled trials (SCORPIO, ARIES, CAPRICORN). Patients completed a micturition diary, EQ-5D and OAB-q (a quality of life questionnaire from which OAB-5D is derived) at baseline and at weeks 4, 8 and 12. Time trade-off tariffs elicited from UK population were applied to obtain utilities from both instruments. Repeated measures regressions were used to estimate EQ-5D and OAB-5D utilities by micturition frequency and incontinence severity level. As a test of sensitivity of the instruments, utility changes from baseline to week 12 were estimated by symptomatic response (improvement, stable or worsening).ResultsThe sample included 4427 patients. Mean utilities (± standard deviation) across all visits were 0.82 (±0.21) for EQ-5D and 0.86 (±0.09) for OAB-5D. Correlation between EQ-5D and OAB-5D was 0.34 (p < 0.0001). Both OAB-5D and EQ-5D utilities increased as OAB symptoms improved. Utility values were similar for severe levels of symptoms, but higher with OAB-5D than with EQ-5D for mild cases. Micturitions and incontinence had similar impact on EQ-5D utilities, but micturitions had greater impact on OAB-5D utilities than incontinence. Changes from baseline in OAB-5D utilities differed significantly according to symptomatic response. Changes in EQ-5D utilities were not significantly associated with changes in micturition frequency and weakly associated with changes in incontinence severity among patients with mild symptoms at baseline.ConclusionsThis study showed that both EQ-5D and OAB-5D can detect changes in severity of OAB, especially in severe cases. However, OAB-5D is more sensitive than EQ-5D in measuring differences between treatments in milder cases. Both OAB-5D and EQ-5D–although leading to different results–may be useful to derive utilities from clinical trial data and perform cost-effectiveness analyses.Trial registrationClinical Trials NCT00689104, NCT00662909, NCT00912964.

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom

BACKGROUND Mirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB). OBJECTIVES To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective. METHODS A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed. RESULTS Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity. CONCLUSIONS Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.

Validation of the first quality-of-life measurement for patients with Huntington's disease: The Huntington quality of life instrument

Health-related quality-of-life instruments are critical for assessing disease burdens. Generic tools allow comparison between diseases but do not discriminate between disease severities. Specific tools also tend to be more sensitive. No specific tool is available to assess quality of life in patients with Huntington’s disease (HD). In the context of the European study on HD burden, a specific tool was created: the Huntington Quality of Life Instrument (H-QoL-I). The aim of this study was to optimize the content and validate the H-QoL-I. After a semistructured interview with patients, caregivers and HD specialists, we conducted a patient focus group. A self-reported questionnaire was then developed in French and Italian. A total of 252 patients were recruited to answer the questionnaire. Face, internal and external validities were examined using a variety of methods. The shortened H-QoL-I that resulted from the successive analyses comprises 11 items, which are divided into three dimensions: motor functioning (four items), psychology (four items) and socializing (three items). These three domains were identified as being essential to cover the full domain of the quality of life for patients affected by HD. The H-QoL-I showed an acceptable reliability (Cronbach’s &agr;>0.84). Factor analyses demonstrated satisfactory construct validity. Moreover, the item internal consistency and item discriminant validity criteria were fulfilled. No differential item functioning was detected. External validity supported the scale’s robustness. These data support the validity of the H-QoL-I in patients with HD.

A prospective study of health care resource utilisation and selected costs of schizophrenia in France

BackgroundSchizophrenia is among the most burdensome and costly illnesses worldwide. To estimate the cost of schizophrenia in France, a longitudinal study was carried out between 1998 and 2002. The main objective of this study was to describe and update the cost of schizophrenia in a longitudinal, representative sample of French patients. The second objective was to identify cost drivers in the treatment of schizophrenia.MethodsBased on a cohort of 288 French schizophrenic patients during 2 years of prospective follow-up, this study collected clinical, patient reported outcomes, quality of life, functioning, patient management, care giver involvement and resource utilisation data every 6 months. For each service, information was collected on the type of service, the frequency of attendance and type of intervention provided to the patient. Unit costs were based on available French databases. Mean service use and costs over the five time points were estimated using between-effects regression models.ResultsIn the total sample of 288 patients aged 18-64 years, the mean total cost (€ 3 534) was mainly accounted for by the cost of inpatient treatment (€ 1 390) and day care (€ 1 331). The estimate of the annual cost for direct medical health care for all French schizophrenic patients was € 1 581 million, including € 621 million for inpatient treatment and € 595 million for day care (77%). The costs for medication accounted for 16.1% of total annual costs. The remaining costs (6.9%) included visits to psychiatrists, general practitioners, other physicians and psychologists. The direct resource allocation showed inpatient treatment as the main direct cost. Unemployment was identified as a major indirect cost of schizophrenia treatment. Positive and depressive schizophrenia symptoms at baseline and relapse occurrence during the follow-up period were associated with a higher cost of treatment. Health satisfaction or negative symptoms of schizophrenia at baseline were associated with lower costs.ConclusionSeveral cost drivers were identified. Based on the results obtained in France, we suggest further analysis of mechanisms that influence the service-specific costs for schizophrenia in other areas of the world.

A comparison of HAS & NICE guidelines for the economic evaluation of health technologies in the context of their respective national health care systems and cultural environments

Background Health technology assessment (HTA) has been reinforced in France, notably with the introduction of economic evaluation in the pricing process for the most innovative and expensive treatments. Similarly to the National Institute for Clinical Excellence (NICE) in England, the National Authority for Health (HAS), which is responsible for economic evaluation of new health technologies in France, has published recommendations on the methods of economic evaluation. Since economic assessment represents a major element of HTA in England, exploring the differences between these methodological guidelines might help to comprehend both the shape and the role economic assessment is intended to have in the French health care system. Methods Methodological guidelines for economic evaluation in France and England have been compared topic-by-topic in order to bring out key differences in the recommended methods for economic evaluation. Results The analysis of both guidelines has revealed multiple similarities between France and England, although a number of differences were also noted regarding the elected methodology of analysis, the comparison of studies’ outcomes with cost-effectiveness thresholds, the study population to consider, the quality of life valuation methods, the perspective on costs, the types of resources considered and their valuation, the discount rates to apply in order to reflect the present value of interventions, etc. To account for these differences, modifications will be required in order to adapt economic models from one country to the other. Conclusions Changes in HTA assessment methods occur in response to different challenges determined by the different philosophical and cultural considerations surrounding health and welfare as well as the political considerations regarding the role of public policies and the importance of their evaluation.