Study to determine relevant health outcome measures in opioid use disorder: Multicriteria decision analysis. / Estudio para la determinación de medidas de resultados en salud relevantes en el trastorno por consumo de opiáceos. Análisis de decisión multicriterio.

The aim of the current study was to establish the most relevant health outcomes to assess opioid substitution treatment programmes (OSP) in patients with opioid use disorder (OUD) in Spain. A multicriteria decision analysis was applied in 3 phases: 1) concepts and criteria definitions; 2) criteria screening and weighting by means of a discrete choice experiment; 3) deliberative process. Criteria established in phase 1 were: substance use (opioids, alcohol, tobacco, stimulants and cannabis), other mental disorders (affective/anxiety disorder, psychosis, attention deficit hyperactivity disorder, borderline personality disorder, antisocial personality disorder, gambling disorder and other impulse control disorders), level of disability, adherence, medical illnesses (medical comorbidities, risk behaviours, infectious and sexually transmitted diseases), psychosocial aspects (hostile and/or violent behaviour and work problems), functional disability (quality of life, treatment and service satisfaction, social functionality). In phase 2, the most relevant factors in OSP were determined, and subsequently assessed in the deliberative process: remission of substance use (opioids, alcohol and stimulants), improvement of other mental disorders (psychosis and borderline personality disorder), improvement in comorbidity management, and improvement in social functionality, with a weighting of 56.5%, 21.9%, 11.0%, and 10.7%, respectively. The current analysis defines the main health outcomes in OSP in patients with OUD in Spain, supporting decision making and socio-health management of existing resources.

El objetivo fue establecer los resultados en salud con mayor relevancia en la evaluación de programas de tratamiento de sustitución de opiáceos (PTSO) en pacientes con trastorno por consumo de opiáceos (TCO) en España. Se realizó un análisis de decisión multicriterio con 3 fases: 1) definición de conceptos y criterios a evaluar; 2) cribado y ponderación de criterios mediante un experimento de elecciones discretas; 3) proceso deliberativo. Los criterios de la fase 1 fueron: consumo de sustancias (opiáceos, alcohol, tabaco, estimulantes y cannabis), trastornos mentales (trastorno afectivo ansioso, psicosis, trastorno por déficit de atención e hiperactividad, trastorno límite de personalidad, trastornos de personalidad antisocial, trastorno por juego y otras alteraciones del control de los impulsos), nivel de discapacidad, adherencia, enfermedades médicas (comorbilidades, conductas de riesgo, enfermedades infecciosas y de transmisión sexual), aspectos psicosociales (conducta hostil y/o violenta, presencia de problemas laborales), discapacidad funcional (calidad de vida, satisfacción con el tratamiento y servicio, funcionamiento social). En la fase 2 se determinaron los factores fundamentales en la elección de un PTSO, revisados en el proceso deliberativo: remisión del consumo de sustancias (opiáceos, alcohol y estimulantes), mejoría en el manejo de otros trastornos mentales (psicosis y trastorno límite de la personalidad), mejoría en manejo de comorbilidades médicas y mejoría en el funcionamiento social, con un peso del 56,5%, 21,9%, 11,0% 10,7% respectivamente. Este análisis define los resultados sanitarios más relevantes en PTSO en pacientes con TCO en España, favoreciendo la toma de decisiones y la gestión socio-sanitaria de los recursos existentes.

Effect of a Mobile App on Preoperative Patient Preparation for Major Ambulatory Surgery: Protocol for a Randomized Controlled Trial.

BACKGROUND: Inadequate preoperative patient preparation causes organizational, economic, and emotional problems to patients and professionals. In Spain, no current evidence is available on either the rate of compliance or the impact of good compliance with preoperative recommendations by patients in the ambulatory setting. However, it is known that around 25% of surgical cancellations in the major ambulatory surgery (MAS) are due to poor compliance with these recommendations and, therefore, avoidable. Introducing innovative tools based on mobile health (mHealth) apps may help patients meet the preoperative recommendations and, consequently, reduce the rate of cancellations in the ambulatory setting. OBJECTIVE: The objective of this study was to evaluate the effectiveness of the Listeo+ mHealth app as a tool for improving compliance with preoperative recommendations in MAS versus standard of care (SOC). METHODS: A multicenter, randomized, open-label clinical trial that compares SOC with the additional use of Listeo+, a specific mHealth app for MAS preoperative patient monitoring, is being conducted. The study will include patients aged ≥18 years with surgical indication for MAS who meet the necessary technological and connectivity requirements. Patients in the control group will receive written preoperative recommendations, while those in the intervention group will additionally use the Listeo+ mHealth app. There will be a competitive recruitment of 790 patients during 6 months in 4 hospitals in Andalusia (Spain) that belong to the National Health System. The primary efficacy outcome is the level of compliance with preoperative recommendations. Secondary outcomes include the rate of cancellations, associated resource consumption, and perceived usability and utility with Listeo+ by participants of the intervention group. Simple randomization 1:1 procedure will be used to allocate patients to each study group. RESULTS: The technological development of Listeo+ and the integration and interoperability of information systems was completed in September 2017. Subsequently, simulation tests were performed with Listeo+, and a pilot study was initiated with real patients that concluded successfully in October 2017. Patient recruitment began in December 2017 in the 4 participating centers. After an intermediate analysis performed 10 months after the start of the recruitment phase, the data collection and cleaning phases are estimated to be completed in April 2019, and the analysis with the final results will be conducted in July 2019. CONCLUSIONS: Progress in the integration and interoperability of information systems represents a major step forward in the field of mHealth. The app will allow health professionals to monitor in real-time patients' preparation and critical preoperative recommendations fulfillment. We expect a reduction in avoidable preoperative cancellations due to a lack of or a poor patient preparation. Self-assessed Web-based questionnaires and focus group will provide important information about the perceived usability and utility of Listeo+ app among patients and health care professionals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10938.

Healthcare value of implementing hepatitis C screening in the adult general population in Spain.

BACKGROUND: Elimination of hepatitis C virus (HCV) infection requires high diagnostic rates and universal access to treatment. Around 40% of infected individuals are unaware of their infection, which indicates that effective screening strategies are needed. We analyzed the efficiency (incremental cost-utility ratio, ICUR) of 3 HCV screening strategies: a) general population of adults, b) high-risk groups, and c) population with the highest anti-HCV prevalence plus high-risk groups. METHODS: An analytical decision model, projecting progression of the disease over a lifetime, was used to establish the candidate population for HCV screening. HCV data were obtained from the literature: anti-HCV prevalence (0.56%-1.54%), viremic patients (31.5%), and percentage of undiagnosed persons among those with viremia (35%). It was assumed that most patients would be treated and have HCV therapy response (98% SVR); transition probabilities, utilities, and disease management annual costs were obtained from the literature. Efficiency over the life of patients under the National Health System perspective was measured as quality-adjusted life years (QALY) and total cost (screening, diagnosis, pharmacological and disease management). A discount rate of 3% was applied to costs and outcomes. RESULTS: Screening of the adult population would identify a larger number of additional chronic hepatitis C cases (N = 52,694) than screening the highest anti-HCV prevalence population plus high-risk groups (N = 42,027) or screening high-risk groups (N = 26,128). ICUR for the general population vs. high-risk groups was €8914/QALY gained per patient (€18,157 incremental cost and 2.037 QALY). ICUR for the general population vs. population with highest anti-HCV prevalence plus high-risk groups was €7,448/QALY gained per patient (€7,733 incremental cost and 1.038 QALY). These ICUR values are below the accepted efficiency threshold (€22,000-€30,000). CONCLUSION: HCV screening and treatment of the general adult population is cost-effective compared to screening of high-risk groups or the population with the highest anti-HCV prevalence plus high-risk groups.

Análisis de decisión multicriterio en programas de tratamiento de sustitución de opiáceos en trastornos por consumo de opiáceos. / Análisis de decisión multicriterio en programas de tratamiento de sustitución de opiáceos en trastornos por consumo de opiáceos.

Editorial.

Editorial.

Análisis de decisión multicriterio en programas de tratamiento de sustitución de opiáceos en trastornos por consumo de opiáceos / Multicriteria decision analysis in opioid substitution treatment programs in opioid use disorders

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Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

BACKGROUND: Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. OBJECTIVE: The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. METHODS: A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. RESULTS: Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. CONCLUSION: First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost savings and higher health benefits for the Spanish NHS.

Cost analysis of glatiramer acetate vs. fingolimod for the treatment of patients with relapsing-remitting multiple sclerosis in Spain.

BACKGROUND: Fingolimod is an innovative drug with a significant budget impact in the treatment of MS in Spain. The aim of this study was to calculate the direct cost comparison of glatiramer acetate and fingolimod for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) in Spain. METHODS: A cost analysis model was developed to compare glatiramer acetate and fingolimod, based on a 1-year time horizon. In addition to the pharmacological costs, resource use was estimated for glatiramer acetate (1 hour of training with nursing staff in self-injection techniques for subcutaneous administration) and fingolimod (vaccination for varicella-zoster virus in 5% of patients, 3 complete blood counts per year, 3 ophthalmology visits for prevention of macular edema, 3 transaminase tests to monitor liver function, and cardiovascular monitoring consisting of 1 ECG before the first fingolimod dose and at 6 hours; 1 day outpatients-hospital visit for cardiological monitoring during 6 hours on the day of the first fingolimod dose, with follow-up of blood pressure and heart rate every hour). The pharmacological costs were calculated based on the ex-factory price of the drugs evaluated, using the doses recommended in the respective Summary of Products Characteristics (SmPC). Total invoicing volume was discounted by 7.5%, as laid down in Spanish Royal Decree 8/2010. Unit costs were obtained from the e-Salud database and the drug catalog. Costs in the model are expressed in €2012. RESULTS: The cost of annual treatment was €9,439.42 for glatiramer acetate and €19,602.18 for fingolimod, yielding a cost difference of €10,162.76. Assuming a fixed budget of €100,000.00, approximately 10 patients could be treated with glatiramer acetate, compared to 5 with fingolimod. CONCLUSIONS: Fingolimod therapy requires twice the investment as glatiramer acetate.

Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain.

BACKGROUND: Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial µ-opiod agonist and a κ-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. METHODS: A budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros (€, 2010). RESULTS: The number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is €85,766,129; €79,855,471 and €79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be €86,589,210; €80,398,259 and €79,708,964 in the first, second and third year of the analyses. Incremental cost/patient comparing the addition of the B/N combination to the scenario only with methadone is €10.58; €6.98 and €7.34 in the first, second and third year respectively. CONCLUSION: Addition of B/N combination would imply a maximum incremental yearly cost of €10.58 per patient compared to scenario only with methadone and would provide additional benefits.

Cost effectiveness of prostacyclins in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is considered an orphan disease. Prostacyclins are the keystone for PAH treatment. Choosing between the three available prostacyclin therapies could be complicated because there are no comparison studies, so the final decision must be driven by factors such as efficacy, administration route, safety profile and economic aspects. OBJECTIVE: This study provides a cost-effectiveness and cost-utility comparison of initiating prostacyclin therapy with three different treatment alternatives (inhaled iloprost [ILO], intravenous epoprostenol [EPO] and subcutaneous treprostinil [TRE]) for patients with PAH. The goal of this work is to help physicians with their therapeutic decision-making. METHODS: A Markov model was built to simulate a patient cohort with class III PAH according to the classification of the New York Heart Association (NYHA). Four health states corresponding with the NYHA classes plus death were allowed for patients in the model. Changing the treatment was possible when patients worsened from functional class III to IV. The time horizon was 3 years, allowing patients to transition between health states on a 12-week cycle basis. The study perspective was that of the National Health System (NHS) [only direct medical costs were included]. Unitary costs were obtained from the Drug Catalogue and e-Salud Database in 2009 and are given in euros (€). Data on health resources and treatment pathways were informed by a four-member expert panel. Efficacy was obtained from pivotal clinical trials of ILO, EPO and TRE, the latter used in Spain as a foreign medication. Utilities for each health state were obtained from the literature. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). Costs and effects were discounted at a 3% rate. To check for the robustness of the results, sensitivity analyses were performed. RESULTS: At the end of the 3 years, in the base case of the deterministic analysis, initiating prostacyclin therapy with iloprost was the less costly strategy (€132,840), followed by treprostinil (€359,869) and epoprostenol (€429,775). Epoprostenol has shown the best efficacy results with 2.73 LYG and 1.78 QALY, followed by iloprost (2.69 LYG and 1.74 QALY) and treprostinil (2.69 LYG and 1.73 QALY). Incremental cost-effectiveness ratios (ICER) and cost-utility ratios (ICUR) of epoprostenol versus iloprost and treprostinil were much above the €30,000 per LYG or QALY threshold commonly used in Spain. Iloprost was dominant compared with treprostinil. In the probabilistic analysis, epoprostenol, when compared with iloprost, was a dominant strategy in 15% of the simulations, but it was not a cost-effective option in 83% of the cases. When compared with treprostinil, epoprostenol was dominant in 43% of the simulations. Iloprost was dominant compared with treprostinil in 45% of the cases and it was a cost-effective alternative in 39% of the simulations. CONCLUSIONS: Initiating prostacyclin treatment with iloprost in patients with PAH, functional class III of the NYHA, is the less costly alternative for the NHS in Spain, with a good efficacy profile when compared with the other alternatives.

Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients.

UNLABELLED: Abstract Objective: The aim of this study was to assess cost-effectiveness of the different Disease Modifying Drugs (DMD) used as first-line treatments (interferons IM IFNß-1a, SC IFNß-1a, SC IFNß-1b, and glatiramer acetate, GA) in Remitting-Relapsing Multiple Sclerosis (RRMS) in Spain. METHODS: A Markov model was developed to simulate the progression of a cohort of patients with RRMS, during a period of 10 years. Seven health states, defined by the Expanded Disability Status Scale (EDSS), were considered in the model. Patients with an EDSS score less than 6.0 were assumed to be treated with one of the DMD. In addition, all patients were assumed to receive symptomatic treatment. The monthly transition probabilities of the model were obtained from the literature. The analysis was performed from the societal perspective, in which both direct and indirect (losses in productivity) healthcare costs (€, 2010) were included. A discount rate of 3% was applied to both costs and efficacy results. RESULTS: GA was the less costly strategy (€322,510), followed by IM IFNß-1a (€329,595), SC IFNß-1b (€ 333,925), and SC IFNß-1a (€348,208). IM IFNß-1a has shown the best efficacy results, with 4.176 quality-adjusted life years (QALY), followed by SC IFNß-1a (4.158 QALY), SC IFNß-1b (4.157 QALY), and GA (4.117 QALY). Incremental costs per QALY gained with IM IFNß-1a were €-1,005,194/QALY, €-223,397/QALY, and €117,914/QALY in comparison to SC IFNß-1a, SC IFNß-1b, and GA, respectively. CONCLUSIONS: First-line treatment with GA is the less costly strategy for the treatment of patients with RRMS. Treatment with IM IFNß-1a is a dominant strategy (lower cost and higher QALY) compared with SC IFNß-1a and SC IFNß-1b. However, IM IFNß-1a is not a cost-effective strategy vs GA, because incremental cost per QALY gained with IM IFNß-1a exceeds the €30,000 per QALY threshold commonly used in Spain. LIMITATIONS: The highly-restrictive inclusion criteria of clinical trials limits generalization of the results on efficacy to all patients with multiple sclerosis. Availability of data for head-to-head comparisons is associated with the use of information from clinical trials.

Análisis del impacto presupuestario del tratamiento en primera línea de la esclerosis múltiple remitente recurrente en España / Budget impact analysis of the first-line treatment of relapsing remitting multiple sclerosis in Spain

Objetivo. Estimar el impacto presupuestario de los tratamientos en primera línea de la esclerosis múltiple remitente recurrente (EMRR) con interferones y acetato de glatiramero desde la perspectiva del Sistema Nacional de Salud en España. Pacientes y métodos. Se diseñó un modelo de análisis del impacto presupuestario para comparar durante cinco años, según diferentes porcentajes de administración de cada uno de los medicamentos, los costes de un escenario de referencia (caso base) en el que se incluyen los tratamientos en primera línea (interferones y acetato de glatiramero), frente a cinco escenarios alternativos en el que se excluyen cada uno de estos tratamientos. La evaluación de los costes (en euros del año 2010) incluyó los recursos médicos directos (medicación, administración, manejo de la enfermedad, tratamientos concomitantes, visitas, pruebas diagnósticas). Los datos de costes unitarios se tomaron de la base de datos de costes sanitarios e-Salud y del Catálogo de Medicamentos. Resultados. Considerando una cohorte de 22.255 pacientes con EMRR, el impacto global promedio por año sería de 260.775.470 euros en el caso base. El escenario alternativo en el que se produce un mayor incremento del impacto total es cuando se excluye acetato de glatiramero, aumentando en un 3,23% (372 euros por paciente y año). El coste farmacológico supone la mayor parte del coste global (90%). Conclusión. La utilización de acetato de glatiramero en el tratamiento de primera línea de pacientes con EMRR es una estrategia que conlleva un ahorro de costes, lo que permitiría una disminución del impacto presupuestario desde la perspectiva del Sistema Nacional de Salud en España (AU)

Aim. To assess the budget impact of the treatment for relapsing remitting multiple sclerosis (RRMS), interferons, and glatiramer acetate, from the National Health System perspective in Spain. Patients and methods. A budget impact model was designed to compare the cost of RRMS treatment in different settings,using a five year time-horizon, considering different percentages of administration of each medication. A reference setting o base case using all the available first line treatments (interferons and glatiramer acetate) was compared with five alternatives scenarios excluding each one of these treatments. The cost analysis (euros, year 2010) includes direct medical resources (drugs, administration, visits, disease management, diagnostic tests). Unitary cost data was obtained from the health costs database e-Salud and drugs catalogue. Results. Considering a cohort of 22 255 patients with RRMS, the mean global budget impact per year would be 260 775 470 euros in the base case. The setting that excluded glatiramer acetate increases the budget impact in a 3.23% (372 euros per patient per year). Pharmacological costs were the key drivers of total cost (90%). Conclusion. The use of glatiramer acetate in the first-line-treatment of RRMS patients is a cost-saving strategy, which may decrease the budget impact from the National Health System perspective in Spain (AU)

Efficacy of taxanes as adjuvant treatment of breast cancer: a review and meta-analysis of randomised clinical trials.

OBJECTIVES: To evaluate the magnitude of benefit obtained by taxanes as adjuvant treatment of breast cancer and to assess the best method for their administration. MATERIAL AND METHODS: We performed a systematic search of phase III randomised clinical trials that included patients with non-metastatic breast cancer in whom comparisons were chemotherapy (CT) containing a taxane (docetaxel or paclitaxel) vs. CT without taxanes (first-generation trials), or CT with taxane in both treatment arms (second-generation trials), administered after surgery. The parameters of efficacy evaluated were disease-free survival (DFS) and overall survival (OS). The data obtained in the first-generation trials (number of relapses and deaths) were submitted to a meta-analysis. The odds ratio (OR) combined with DerSimonian and Laird (OR DL) and 95% confidence interval (95% CI) were calculated. Further, an analysis was performed of those trials that included only patients with nodal involvement (N+). In both cases, the results were also analysed as a function of the taxane used, and with indirect comparisons between the two. The second-generation trials were analysed to assess the optimum method of administration. RESULTS: A total of 17 trials were selected for the meta-analysis (30,672 patients). The OR DL was 0.82 (95%CI: 0.76-0.88) for DFS and 0.83 (95% CI: 0.75-0.91) for OS. In N+ patients the results were 0.80 (95% CI: 0.74-0.86) and 0.79 (95% CI: 0.69-0.89), respectively. Docetaxel and paclitaxel significantly increased the DFS and OS. In our indirect comparison, the benefit of docetaxel on OS was significantly superior to that obtained with paclitaxel in N+ patients (OR: 0.79; 95% CI: 0.63-0.98). CONCLUSIONS: The administration of adjuvant CT-based taxanes reduces the risk of relapse and death. This reduction is superior in clinical trials that included only N+ patients. With the available evidence, it would appear that the best method of administering paclitaxel is weekly and for docetaxel tri-weekly.