A multi-criteria decision analysis on the value of nintedanib for interstitial lung diseases.

OBJECTIVES: Our aim was to assess the value of nintedanib for non-idiopathic progressive fibrosing interstitial lung disease (non-IPF PF-ILD) and systemic sclerosis-associated ILD (SSc-ILD) in the Spanish context, using a multi-criteria decision analysis (MCDA). METHODS: Following an adaptation of the Evidence and Value: Impact on DEcision Making (EVIDEM) MCDA methodology, the estimated value of nintedanib was obtained by means of an additive linear model that combined individual weights (100-points distribution) of criteria with the individual scoring of nintedanib in each criterion for every indication, assigned by a multidisciplinary committee of twelve clinicians, patients, pharmacists, and decision-makers. To assess the reproducibility, an alternative weighting method was applied, as well as a re-test of weights and scores at a different moment of time. RESULTS: The experts committee recognized nintedanib as an intervention with a positive value contribution in comparison to placebo for the treatment of non-IPF PF-ILD (0.50 ± 0.16, on a scale from -1 to 1) and SSc-ILD (0.40 ± 0.12), diseases which were considered as very severe and with high unmet needs. The drug was perceived as a treatment that provides an added therapeutic benefit for patients (0.06-0.07), given its proven clinical efficacy (0.05-0.06), slight improvements in patient-reported outcomes (0.01-0.02), and similar safety profile than placebo (-0.04-0.00), which will likely be positioned as a recommended therapy in the next clinical practice guidelines updates. CONCLUSIONS: Under this increasingly used methodology, nintedanib has shown to provide a positive value estimate for non-IPF PF-ILD and SSc-ILD when compared to placebo in Spain.

Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population.

BACKGROUND: Eribulin's clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. PATIENTS AND METHODS: This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. RESULTS: A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1-11.4) and 2.8 months (95% confidence interval: 2.5-3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3-4.5) versus triple negative: 2.0 (95%confidence interval: 1.7-2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6-12.5 vs. 4.8 months, 95% confidence interval: 3.4-6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1-16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8-5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. CONCLUSION: Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature.

BACKGROUND: Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. METHODS: PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000-2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. RESULTS: Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. DISCUSSION: ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. CONCLUSIONS: ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.

Recent Advances in the Management of Patients with Non-Muscle-Invasive Bladder Cancer Using a Multidisciplinary Approach: Practical Recommendations from the Spanish Oncology Genitourinary (SOGUG) Working Group.

On the basis of the discussion of the current state of research on relevant topics of non-muscle-invasive bladder cancer (NMIBC) among a group of experts of the Spanish Oncology Genitourinary (SOGUG) Working Group, recommendations were proposed to overcome the challenges posed by the management of NMIBC in clinical practice. A unified definition of the term 'microhematuria' and the profile of the patient at risk are needed. Establishing a 'hematuria clinic' would contribute to a centralized and more efficient evaluation of patients with this clinical sign. Second or repeated transurethral resection (re-TUR) needs to be defined, including the time window after the first procedure within which re-TUR should be performed. Complete tumor resection is mandatory when feasible, with specification of the presence or absence of muscle. Budding should be used as a classification system, and stratification of T1 tumors especially in extensive and deep tumors, is advisable. The percentage of the high-grade component should always be reported, and, in multiple tumors, grades should be reported separately. Luminal and basal subtypes can be identified because of possibly different clinical outcomes. Molecular subtypes and immunotherapy are incorporated in the management of muscle-invasive bladder cancer but data on NMIBC are still preliminary.

Cost of Venous Thromboembolic Disease in Patients with Lung Cancer: Costecat Study.

BACKGROUND: Patients with lung cancer (LC) are at significantly higher risk of developing venous thromboembolism (VTE), which may lead to increased use of health resources and the cost of management. The main aim of the study was to determine the cost of the management of VTE events in patients with LC treated with Low Molecular Weight Heparins (LMWH) in Spain. METHODS: Costecat was an, observational, ambispective pharmacoeconomic study. Patients with LC, with a first episode of VTE (symptomatic or incidental) in treatment with LMWH, were recruited from six third-level hospitals and followed up for six months. Sociodemographic, clinical and resource use variables of VTE-related implications and its treatment were collected. Direct healthcare costs and direct non-healthcare costs were recorded. Data collection was documented in an electronic case report. Unit costs were obtained from national databases. Costs (€2018) were estimated from the healthcare perspective. Statistical analysis was performed using the statistical program R 3.4.3 version (30 November 2017). RESULTS: Forty-seven patients were included. Mean age was 65.4 years, 66.0% were male. The percentage of patients with LC who had metastatic disease was 78.7%. Twenty-three patients (48.9%) needed hospital admissions due to thromboembolic episode. Total average cost of patients with cancer associated VTE (CAT) was €109,696.6 per patient/semester. The hospitalizations represent 65.8% of total costs (7207.3 € SD 13,996.9 €), followed by LMWH therapy which represents 18.6% (2033.8 € SD:630.5 €). CONCLUSIONS: Venous thromboembolism episodes induce an economic impact on patients and healthcare systems. Direct healthcare costs are the major burden of the total cost, in which hospitalizations are the main drivers of cost.

MULTI-CRITERIA DECISION ANALYSIS AS A DECISION-SUPPORT TOOL FOR DRUG EVALUATION: A PILOT STUDY IN A PHARMACY AND THERAPEUTICS COMMITTEE SETTING.

OBJECTIVES: The aim of this study was to develop and to assess a specific Multi-Criteria Decision Analysis (MCDA) framework to evaluate new drugs in an hospital pharmacy and therapeutics committee (P&TC) setting. METHODS: A pilot criteria framework was developed based on the EVIDEM (Evidence and Value: Impact on DEcisionMaking) framework, together with other relevant criteria, and assessed by a group of P&TC's members. The weighting of included criteria was done using a 5-point weighting technique. Two drugs were chosen by evaluation: an orphan-drug for Gaucher disease, and a nonorphan drug for the treatment of inflammatory bowel disease. Evidence matrices were developed, and value contribution of each drug was evaluated by P&TC's members. An agreed final framework was obtained through a discussion between the P&TC's members. RESULTS: After criteria assessment, the pilot framework included eight quantitative criteria: "disease severity," "unmet needs," "comparative efficacy/effectiveness," "comparative safety/tolerability," "comparative patient-reported outcomes," "comparative cost consequences-cost of treatment," "comparative cost consequences-other medical costs," and "quality of evidence"; and one contextual criterion: "opportunity costs and affordability." The most valued criteria were: "comparative safety/tolerability," "disease severity," and "comparative efficacy/effectiveness." When assessing the drugs most valued characteristics of the MCDA were the possibility that all team may contribute to drug assessment by means of scoring the matrices and the discussion to reach a consensus in drug positioning and value decision making. CONCLUSIONS: The reflective MCDA would integrate quantitative and qualitative criteria relevant for a P&TC setting, allowing reflective discussions based on the criteria weighting score.

Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I.

The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients' leucocytes were studied: enzyme activity at 15 min. post-infusion (Act75 ) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act75-0 ) indicates the total drug exposure during infusion. The clinical response was evaluated based on criteria established by Pastores et al. and Gaucher Severity Score Index. Statistical analysis included ROC analysis and area under the curve test. Act75 and Act75-0 were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act75 was 0.733 and Act75-0 was 0.817). Act75-0 showed statistical significance in its discriminative capacity (p < 0.05) for obtaining an optimal response to ERT. The cut-off point was 58% (RR = 1.800; 95% CI: 1.003-3.229; p < 0.05). Moreover, Act75 showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act75 and Act75-0 presented a significant correlation with residual enzyme activity at diagnosis. Markers based on glucocerebrosidase activity have a good correlation with clinical response to ERT. Therefore, it could provide supporting clinical data for dose management in GD1 patients.

[Oral chemotherapy: food-drug interactions]. / Administración de citostáticos vía oral: interacciones fármaco-alimento.

INTRODUCTION: oral chemotherapy is increasingly used in Oncology. It has important advantages. such as patient comfort. but it also brings new challenges which did not exist with the intravenous therapy. Some of these drugs have interactions with food. leading to changes in their bioavailability. As they are drugs of narrow therapeutic margin. this can lead to alterations in their efficacy and/or toxicity. OBJECTIVES: A. Assessing the level of knowledge on the administration of oral cytostatics that present restrictions with meals (drugs that have to be taken with/without food) among the outpatients. B. Minimizing the incorrect administration and the risk of food-drug interactions. providing patients with information as to how and when drugs have to be administrated. METHODS: once the oral cytostatics with food restrictions were identified. we asked the patients in treatment about the information they had received from the doctor and the way they were taking the medication. We provided those who were taking the drug incorrectly with the right information. In the following visit. it was confirmed if the patients that had been previously taking the cytostatic incorrectly. were taking them in a correct way (intervention accepted/not accepted). RESULTS AND CONCLUSIONS: 40% of the patients interviewed used to take the drug incorrectly. We detected a great diversity depending on the dispensed drug. 95% of the 39 interventions made were accepted. The data obtained suggest the need to reinforce the information that the patient receives. It is important to make sure that the patient understands how and when the oral cytostatic should be administered.

Introducción: el uso de citostáticos orales está cada vez más extendido en oncología. Presenta ventajas importantes, como la comodidad para el paciente, pero también supone nuevos retos que no se planteaban con la terapia intravenosa. Algunos de estos fármacos presentan interacciones con los alimentos, dando lugar a cambios en su biodisponibilidad. Al tratarse de fármacos de estrecho margen terapéutico, pueden dar lugar a alteraciones en su eficacia y/o toxicidad. Objetivos: evaluar el nivel de conocimiento sobre el modo de administración por parte de los pacientes que acuden a la consulta de pacientes externos de oncohematología del hospital de aquellos citostáticos orales que presentan alguna restricción respecto a su consumo con alimentos (deben tomarse o bien en ayunas. o bien con alimentos). Minimizar al máximo la administración incorrecta de los citostáticos dispensados y el riesgo de que se produzcan interacciones con los alimentos, proporcionando información a los pacientes acerca del modo correcto de administración. Material y métodos: una vez identificados los citostáticos orales con restricciones respecto a su consumo con alimentos, además de la información aportada por farmacia, se preguntó a los pacientes la información que habían recibido por parte del médico acerca de cómo debía administrarse el fármaco, el modo en que se lo tomaban finalmente y, en caso de no hacerlo adecuadamente, se les reforzó la información pertinente. En el siguiente ciclo se confirmó si efectivamente el paciente se lo administraba correctamente, en caso de hacerlo previamente de forma incorrecta (intervención aceptada/no aceptada). Resultados y conclusiones: un 40% de los pacientes entrevistados se administraban el fármaco incorrectamente. Los resultados muestran una gran diversidad en función del fármaco dispensado. Se realizaron un total de 39 intervenciones, que fueron aceptadas en un 95%. Los datos obtenidos sugieren la necesidad de reforzar la información que el paciente recibe más allá de la primera visita para asegurarnos de que ha comprendido las condiciones en las que el fármaco debe administrarse.