Cost-effectiveness of olaparib plus bevacizumab versus bevacizumab monotherapy in the maintenance of patients with homologous recombination deficiency-positive advanced ovarian cancer after response to first-line platinum-based chemotherapy.

OBJECTIVE: The PAOLA-1 trial confirmed that adding olaparib to bevacizumab significantly increased clinical benefit following response to platinum-based chemotherapy in homologous recombination deficiency-positive ovarian cancer. The objective of this analysis was to determine the cost-effectiveness of olaparib plus bevacizumab compared with bevacizumab alone as maintenance treatment for patients with homologous recombination deficiency-positive advanced ovarian cancer from the Spanish National Health System perspective. METHODS: A lifetime partitioned survival model with four health states (progression-free, post-progression 1, post-progression 2, and death) and monthly cycles was developed. Long-term survival, defined as 60 months, was included as a landmark to extrapolate progression-free survival from PAOLA-1. Weibull distribution was selected as the most accurate survival model for progression-free survival extrapolation. Time to second progression and overall survival were extrapolated using parametric survival models. Mortality was obtained from the overall survival and adjusted by Spanish women mortality rates. Health state utilities and utility decrements for adverse events were included. An expert panel validated data and assumptions. Direct costs (in 2021 euros (€)) were obtained from local sources and included drug acquisition and administration, subsequent therapies, monitoring costs, adverse events, and palliative care. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio was calculated as cost per quality-adjusted life-years (QALYs) gained. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Compared with bevacizumab alone, olaparib plus bevacizumab increased QALYs and life-years by 2.39 and 2.77, respectively, at an incremental cost of €58 295.31, resulting in an incremental cost-effectiveness ratio of €24 371/QALY. Probabilistic sensitivity analysis demonstrated that olaparib plus bevacizumab had a 49.5% and 90.3% probability of being cost-effective versus bevacizumab alone at a willingness-to-pay threshold of €25 000 and €60 000 per QALY gained, respectively. CONCLUSION: For patients with homologous recombination deficiency-positive advanced ovarian cancer, olaparib plus bevacizumab is a cost-effective maintenance therapy compared with bevacizumab alone in Spain.

Epidemiology of hepatitis C virus infection in a country with universal access to direct-acting antiviral agents: Data for designing a cost-effective elimination policy in Spain.

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost-effectiveness of a screen-and-treat strategy in the Spanish population. A population-based, cross-sectional study (PREVHEP-ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015-April 2017. Participants from three Spanish regions were selected using two-stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti-HCV antibodies/quantify HCV RNA. The cost-effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20-74 (58.4% females), the overall anti-HCV prevalence was 1.2% (95% CI 1.0-1.4), whereas the detectable HCV-RNA prevalence was 0.3% (0.2-0.4). Infection rates were highest in subjects aged 50-74 years [anti-HCV 1.6% (1.3-1.9), HCV RNA 0.4% (0.3-0.6]. Among the 147 anti-HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti-HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost-effective across all age cohorts, particularly in patients aged 50-54 (negative incremental cost-effectiveness ratio which indicates a cost-saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti-HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost-effective across all age cohorts.

Budgetary Impact Analysis of Reimbursement Varenicline for the Smoking-Cessation Treatment in Patients with Cardiovascular Diseases, Chronic Obstructive Pulmonary Disease or Type-2 Diabetes Mellitus: A National Health System Perspective.

AIMS: The study aimed to assess the budgetary impact (BI) of reimbursing varenicline in patients with chronic obstructive pulmonary disease (COPD), type-2 diabetes mellitus (t2-DM) or cardiovascular diseases (CVD). METHODS: The BI was estimated comparing the current non-reimbursed scenario versus a projected reimbursed scenario using the Spanish National Health System (SNHS) perspective. A hybrid model was developed using epidemiological data and Markov chains to estimate smoking cessation rates with varenicline during a 5-year horizon. Costs of cessation were considered in the reimbursement scenario only. Efficacy, expressed as a 1-year continuous abstinence rate, was derived from clinical trials. Cost savings due to smoking cessation were extracted from local cost-of-illness studies. Results are shown as incremental cost savings. Univariate sensitivity analysis was also applied. RESULTS: A total of 68,684 patients stopped smoking in the reimbursed scenario compared with 15,208 without reimbursement. In the reimbursed scenario, total savings accounted for €36.3 million, showing 14.6 million accumulated additional savings compared with the scenario without reimbursement. Sensitivity analyses showed results to be robust with monetary savings starting in the third year of modeling. CONCLUSION: Reimbursement of varenicline in smoking cessation is a cost-effective health policy in the SNHS in COPD, t2-DM or CVD, and could produce cost savings starting in the third year of implementation.

Assessing health-related quality of life in patients with breast cancer: a systematic and standardized comparison of available instruments using the EMPRO tool.

PURPOSE: The objective was to obtain a standardized evaluation of available specific and generic breast cancer health-related quality-of-life instruments. METHODS: We carried out systematic literature reviews in the PubMed and EMBASE databases to identify manuscripts which contained information regarding either the development process or metric properties of health-related quality-of-life instruments used among breast cancer patients. Each instrument was evaluated independently by two researchers, and occasionally a third one, using the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall score and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to best): concept and measurement model, reliability, validity, responsiveness, interpretability, burden, and alternative forms. RESULTS: FACT-B was the instrument with the best global performance, obtaining an overall EMPRO score of 79.27. It was also the most accurate instrument on the Concept and Measurement Model, Reliability, and Interpretability attributes. Four more instruments scored over 50 points on the overall score, which summarizes the five attribute-specific scores: EORTC BR-23, IBCSG, WHO-QOL BREF, and SF-36. An overall score of at least 50 points implies that the use of these instruments could be recommended for assessing health-related quality of life in breast cancer patients. CONCLUSION: The FACT-B scored the highest on overall on our EMPRO evaluation of instruments measuring health-related quality of life among breast cancer patients. However, depending on the purpose of the study, several instruments (EORTC BR-23, IBCSG, SF-36, and WHO-QOL BREF) have shown good performance in some of the specific individual dimensions included in the EMPRO.

Cost-Utility Analysis of Adjuvant Olaparib for Germline BRCA1/2-Mutated, High-Risk HER2-Negative Early Breast Cancer in Spain.

OBJECTIVE: Here we estimate the cost-effectiveness of olaparib in the Spanish National Health Service (SNHS) as adjuvant treatment of early germline mutations in the BRCA1/2 genes (gBRCAm) HER2-negative (HER2neg) breast cancer (BC) with high risk of recurrence. METHODS: A semi-Markov model was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a lifetime horizon. Two scenarios were compared: receiving olaparib versus standard of care (SoC) treatment. The model comprised five health states and included the clinical results of the OlympiA trial, along with the direct healthcare costs associated with the use of early BC and subsequent treatment resources (€2023). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was carried out. RESULTS: The introduction of olaparib as adjuvant treatment for patients with early gBRCAm HER2neg BC with high risk of recurrence could involve an incremental cost of €44,273 and €50,164, with an improvement of 1.14 and 1.28 quality-adjusted life years (QALYs) for hormone receptor-positive (HR+) and triple-negative (TN) patients, respectively. Therefore, adjuvant olaparib could be cost-effective for early gBRCAm HER2neg BC, with an incremental cost-effectiveness ratio of €38,839/QALY and €39,084/QALY for HR+ and TN patients, respectively. The results from the PSA showed that 75.7% and 82.2% of the simulations fell below the €60,000/QALY threshold. CONCLUSIONS: Olaparib as adjuvant treatment could be cost-effective in gBRCAm patients with early HER2neg BC in Spain.

Waveform load analysis for fatigue in the printed PLA.

Additive manufacturing is fast becoming a key process to manufacture a customized design with complex geometry and one process usually employed is based on the fused filament fabrication. Up to now this method is typically employed for rapid prototyping, it is therefore their mechanical strength is lower than the components manufactured using conventional casting process. It is well known that most failures are happened under repeated loads; therefore, a functional component mandatory needs to reach endurance strength under cyclic loads. Hence, this study set out to clarify several aspects of filament fused test specimens to determine their effect on accumulated damage to then predict component life under repeated loads. In this study is considered three waveforms such as sinusoidal, triangular and square, where it is observed that the square waveform provides the most severe loads. This study therefore makes a major contribution to research on the fatigue properties of parts manufactured using fused filament by reporting their fatigue behaviour under different fatigue load conditions. It would give a better understanding to improve the mechanical prediction of PLA, thereby it might be used to manufacture a functional component instead of only a prototype or spare part.

Evaluación de la aptitud clínica al egreso de la Licenciatura de Medicina / Assessment of the clinical aptitude of Medicine Bachelor's degree graduate

OBJETIVO: Analizar la aptitud clínica y su relación con el promedio general (final) en los egresados de la licenciatura de medicina de una institución del sector privado. MÉTODOS: Mediante un estudio transversal y prospectivo se estudiaron a 58 alumnos egresados de la Licenciatura de Medicina. La aptitud clínica se definió operacionalmente como la medición que se obtiene al aplicar un instrumento que explora esta parte de la competencia clínica, basado en casos clínicos reales. La validación del instrumento fue realizada por los profesores de la propia escuela de medicina, quedando la versión definitiva en 320 reactivos. Se exploraron seis indicadores como: identificación de factores de riesgo, reconocimiento de datos clínicos, integración diagnóstica, utilización e interpretación de estudios de laboratorio, decisiones terapéuticas y medidas de seguimiento. Para el análisis de los resultados, se utilizó estadística descriptiva y para obtener la relación entre variables cuantitativas, se realizó el coeficiente de correlación de Pearson. Además se calculó la calificación esperada por azar. RESULTADOS: La consistencia interna del instrumento de medición utilizado fue de 0,82. La correlación del promedio final de la carrera y el nivel de aptitud clínica alcanzada por los alumnos recién egresados de la Licenciatura de Medicina fue de 0,42 (p< 0,01). CONCLUSIONES: Aunque el grado de desarrollo de la aptitud clínica no es el deseable, existe cierto grado de correlación entre el promedio final de la carrera y la aptitud clínica al término del octavo semestre.

OBJECTIVE: To analyze the clinical aptitude and its relation to general average (final) in the graduates of Medicine Bachelor's degree from a private institution. METHODS: A cross-sectional and prospective study was applied in 58 graduate students of Medicine Bachelor's degree. The clinical aptitude was defined operationally as the measurement is obtained by applying an instrument to explore this part of clinical competence, based on real clinical cases. Tool validation was made by professor of the same Medicine school where the definitive version remained in 320 reactives. Six indicators were explored: identification of risk factors, recognition of clinical data, diagnostic integration, use and interpretation of laboratory studies, therapeutical decisions and follow-up measures. For the results analysis we used the descriptive statistics and to obtain the relation among the quantitative variables we performed the Pearson's correlation coefficient. Also, we estimated the random expected qualification. RESULTS: The internal consistency of measurement tool used was of 0,82. Final average correlation of the career and the clinical aptitude level achieved by the newly graduate students of Medicine Bachelor's degree was of 0,42 (p < 0,01). CONCLUSIONS: Although the development level of the clinical aptitude isn't the desirable one, there is come level of correlation between final average of the career and the clinical aptitude at the end of eighth semester.