A Review of Current Approaches to Evaluating and Reimbursing New Medicines in a Subset of OECD Countries.

OBJECTIVES: The aim of this study was to review the current evaluation and funding processes for new drugs in different developed countries, to provide a comparative framework with detailed, homogeneous, and up-to-date information. METHODS: Scientific publications, reports and websites were reviewed between July and December 2021 using PubMed, Google Scholar, and grey literature sources. The main items searched were actors and processes, including timelines, characteristics of clinical and economic evaluations, participation of stakeholders, elements of price and reimbursement decisions, cost-effectiveness thresholds and specific funds. The analysed 13 countries were Australia, Canada, England, France, Germany, Italy, Japan, the Netherlands, Portugal, Scotland, South Korea, Spain and Sweden. RESULTS: Eight countries perform the assessment process separated from the pricing decision. Countries measure each drug's added therapeutic value through multi-attribute value scales, algorithms, non-prescriptive lists of criteria, or quality-adjusted life years (QALYs). Health technology assessment (HTA) methodologies differ in their outcome measures, elicitation techniques, comparators, and perspectives. The criteria used for pricing and reimbursement include humanistic, clinical, and economic aspects. Only Scotland, England, the Netherlands, Canada and Portugal use explicit efficiency thresholds. Health care professionals participate in all assessment committees, and patients are becoming increasingly involved in most countries. The official time from marketing authorisation to the completion of the evaluation and pricing processes varied from 126 to 540 days. CONCLUSIONS: Most analysed countries show a trend towards value-based approaches that consider value for money to society, but also other economic, clinical, and humanistic criteria. Good practices included robustness, transparency, independence, and participation.

Performance of a New Rapid Point-of-Care Test for Infliximab Levels in Patients with Inflammatory Bowel Disease: A Comparison to ELISA.

BACKGROUND: Therapeutic drug monitoring of infliximab levels in patients with inflammatory bowel disease (IBD) optimizes patients' treatment. The reference technique is based on enzyme-linked immunosorbent assay (ELISA) although point of care (POC) assays are being developed. AIMS: To assess the performance of a new rapid immunochromatographic POC assay (Promonitor Quick IFX) compared with ELISA technique to measure infliximab levels in patients with IBD. METHODS: A prospective, observational, unicentric study was performed on capillary blood samples from patients with IBD before infliximab infusion (trough levels). Infliximab levels and anti-infliximab antibodies were measured using the ELISA technique (Promonitor IFX) and the POC assay. Correlation between both techniques was assessed by Pearson's coefficient. Quantitative differences were evaluated by Bland-Altman analysis. Samples were stratified according to infliximab therapeutic ranges (< 3 µg/mL, 3-8 µg/mL, and > 8 µg/mL). RESULTS: A total of 135 experimental samples were assessed. Infliximab levels showed a high correlation between POC and ELISA tests (r = 0.84, P < 0.001). The mean difference between tests was 1.46 µg/mL (P < 0.001), being minimal for concentrations < 8 µg/mL. POC and ELISA assays showed an overall concordance of 87.4%. Most samples were in the same therapeutic range, which lead to equivalent therapeutic decisions. POC and ELISA assays detected the presence of anti-infliximab antibodies in 2.2% and 3.7% of the samples, respectively. CONCLUSIONS: POC assay results in blood samples from patients with IBD were comparable to those obtained with the reference ELISA technique. The POC assay could be considered for routine testing based on its ease of use and rapidity.

Results of treatment with alemtuzumab in a Spanish cohort of patients with multiple sclerosis in the real world: The RealMS study.

Background: Alemtuzumab (ALZ) is a humanized monoclonal antibody approved for the treatment of patients with highly active relapsing-remitting multiple sclerosis (RRMS) administered in two annual courses. The objective of this study was to describe the effectiveness and safety data of ALZ and to report the health resource utilization in patients receiving this treatment. Methods: In this retrospective, non-interventional study, information was retrieved from patients' medical charts at one center in Spain. Included patients were ≥18 years old, and ALZ treatment was initiated between 1 March 2015 and 31 March 2019, according to routine clinical practice and local labeling. Results: Of 123 patients, 78% were women. The mean (standard deviation, SD) age of patients at diagnosis was 40.3 (9.1) years, and the mean time since diagnosis was 13.8 (7.3) years. Patients were previously treated with a median (interquartile range; IQR) number of two (2.0-3.0) disease-modifying treatments (DMTs). Patients were treated with ALZ for a mean (SD) of 29.7 (13.8) months. ALZ reduced the annualized relapse rate (ARR) (1.5 before vs. 0.05 after; p < 0.001) and improved the median EDSS (4.63 before vs. 4.00 after; p < 0.001). Most (90.2%) patients were relapse-free while receiving ALZ. The mean number of gadolinium-enhancing [Gd+] T1 lesions was reduced (1.7 before vs. 0.1 after; p < 0.001), and the mean number of T2 hyperintense lesions was maintained (35.7 before vs. 35.4 after; p = 0.392). A total of 27 (21.9%) patients reported 29 autoimmune diseases: hyperthyroidism (12), hypothyroidism (11), idiopathic thrombocytopenic purpura (ITP) (3), alopecia areata (1), chronic urticaria (1), and vitiligo (1). The mean number of health resources (outpatient visits, emergency room visits, hospital admissions, and tests performed in the hospital) used while patients were treated with ALZ progressively decreased from year 1 to year 4, except for a slight increase at year 2 of outpatient visits. Conclusion: The ReaLMS study provides real-world evidence that ALZ can promote clinical and magnetic resonance imaging disease remission, as well as disability improvement in patients with MS, despite several prior DMT failures. The ALZ safety profile was consistent with data available from clinical trials and other real-world studies. Healthcare resource use was reduced throughout the treatment period.

Budget impact analysis of bevacizumab biosimilars for cancer treatment in adult patients in Spain.

OBJECTIVE: To assess the economic impact of introducing biosimilars of bevacizumab for the management of cancer patients receiving systemic bevacizumab in the National Health System (SNHS) of Spain. METHODS: A 3-year budget impact analysis model was adapted to estimate the cost of introducing biosimilars of bevacizumab in the SNHS for the adult population who were candidates to receive treatment with bevacizumab. Values for the estimation of the population were obtained from the literature and were validated by an expert panel. In this analysis only pharmaceutical costs (€, year 2021) obtained from official databases were considered. A sensitivity analysis was performed to examine the robustness of the model. RESULTS: The introduction of bevacizumab biosimilars would generate an annual cost saving of €11 558 268 (-5.1%) for the first year with a penetration share of biosimilars from 30.0%, €29 126 373 (-8.5%) for the second year with a share of 50.0% and €52 361 778 (-13.6%) for the third year with a share of 80.0%. The total pharmaceutical costs of the scenario without biosimilars are €227 033 352 for the first year, €342 663 209 for the second year and €385 013 076 for the third year. In contrast, the pharmaceutical costs of the scenario with bevacizumab biosimilars are €215 475 084, €313 536 836 and €332 651 297 for years 1, 2 and 3, respectively. CONCLUSIONS: The introduction of biosimilars in the Spanish Health System would generate saving costs in the pharmacological budget to boost biological drugs from the first year.

Feasibility study to characterize price and reimbursement decision-making criteria for the inclusion of new drugs in the Spanish National Health System: the cefiderocol example.

OBJECTIVES: The reimbursement of medicines by the Spanish National Health System (NHS) is based on a set of criteria included in the Royal Legislative Decree 1/2015 (RDL 1/2015). The Interministerial Committee on Pricing of Medicines and Healthcare Products (CIPM) is responsible for the final price and reimbursement (P&R) decision, including on its resolutions the criteria listed in the law by which the reimbursement of a drug is approved or denied. Nevertheless, the information behind its reasoning is not provided. The present study aims to characterize the P&R criteria of the RDL 1/2015 through criteria definitions from other countries to improve the P&R evaluation in Spain. RESULTS: A multidisciplinary experts panel with relevant experience in drug evaluation and decision making at national, regional, and local level in Spain was selected for this study. A literature review to characterize the criteria listed in the RDL 1/2015 was performed based on the most relevant and recognized Health Technology Assessment (HTA) agencies in Europe, UK, and Canada. Eventually, a feasibility study was performed to evaluate the novel drug cefiderocol using the characterized criteria, including a reflective discussion of the results. CONCLUSIONS: Consensus was reached among the multidisciplinary experts on the characterization of the criteria set by the law. The feasibility of their application to a new drug was exploratory, notwithstanding it showed the potential to improve the transparency as well as to offer a more structured rationale for the CIPM to evaluate the inclusion of new drugs in the Spanish NHS.

Real clinical impact of drug-drug interactions of immunosuppressants in transplant patients.

The main objective was to determine the prevalence of real drug-drug interactions (DDIs) of immunosuppressants in transplant patients. We conducted a prospective, observational 1-year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi-Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The causality of DDIs was determined using Drug Interaction Probability Scale. The data were analyzed using Statistical Package for Social Sciences v. 25.0. A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18-79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with antifungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n = 5), followed by hypertension (1.3%; n = 4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non-steroidal anti-inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System.

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems.

Potential clinical biomarkers in rheumatoid arthritis with an omic approach.

OBJECTIVE: To aid in the selection of the most suitable therapeutic option in patients with diagnosis of rheumatoid arthritis according to the phase of disease, through the review of articles that identify omics biological markers. METHODS: A systematic review in PubMed/Medline databases was performed. We searched articles from August 2014 to September 2019, in English and Spanish, filtered by title and full text; and using the terms "Biomarkers" AND "Rheumatoid arthritis". RESULTS: This article supplies an exhaustive review from research of objective measurement, omics biomarkers and how disease activity appraise decrease unpredictability in treatment determinations, and finally, economic, and clinical outcomes of treatment options by biomarkers' potential influence. A total of 122 articles were included. Only 92 met the established criteria for review purposes and 17 relevant references about the topic were included as well. Therefore, it was possible to identify 196 potential clinical biomarkers: 22 non-omics, 20 epigenomics, 33 genomics, 21 transcriptomics, 78 proteomics, 4 glycomics, 1 lipidomics and 17 metabolomics. CONCLUSION: A biomarker is a measurable indicator of some, biochemical, physiological, or morphological condition; evaluable at a molecular, biochemical, or cellular level. Biomarkers work as indicators of physiological or pathological processes, or as a result of a therapeutic management. In the last five years, new biomarkers have been identified, especially the omics, which are those that proceed from the investigation of genes (genomics), metabolites (metabolomics), and proteins (proteomics). These biomarkers contribute to the physician choosing the best therapeutic option in patients with rheumatoid arthritis.

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study).

BACKGROUND: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). METHODS: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders' preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. RESULTS: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%). CONCLUSION: The reimbursement of OMPs in Spain should be determined by its effect on patient's HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs.

The impact of implementing a pharmacy technician role as part of a nursing team in an acute admissions unit.

Background: The National Patient Safety Agency reported over 20 000 safety incidents over a 3-year period, including 68 severe harms and 27 deaths. Dose delays and omissions persistently contributed to more than 50% of the reported incidents. Methods: A pilot was designed and data were collected before and after to measure how these ward-based technician roles affected the reporting of omitted or delayed doses, time efficiency, cost implications and the general productivity of the ward. Results: Three months after the start of the pilot, omitted doses were reduced from 14% to 5% and no incidents of harm had been reported. The 'perfect medication ward round' with no interruptions lasted 23 min compared with the longest medication ward round which lasted 116 min and was interrupted 11 times. Conclusions: The pilot shows that the introduction of pharmacy technicians results in fewer omitted doses and also addresses persistent staffing issues by ensuring better use of nursing time.

Audit of a multidisciplinary approach to improve management of community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a frequent cause of morbidity, mortality and hospital admission worldwide. An adequate choice of empirical antibiotic treatment and appropriate severity assessment of the disease are key aspects in the management of CAP. OBJECTIVE: To audit the adherence to standards of care, such as empirical prescribing of antibiotics, and evaluate the current multidisciplinary approach to the management of CAP. METHOD: Records of patients with CAP were identified and examined for CURB65 score documentation, discussion notes with microbiology and prescribed antibiotic treatments. RESULTS: Out of the 62 patients identified, 32 had a CURB65 score documented in their medical notes and 59 had documented chest X-ray findings. 85.5% of cases were compliant with antibiotic prescribing guidelines. CONCLUSION: The multidisciplinary approach has considerably improved compliance with most of the standards, especially adherence to empirical antibiotic guidelines, and ultimately the standard of care for patients with CAP.

Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar (CT-P13) in patients with inflammatory bowel disease.

BACKGROUND: Infliximab original has changed the natural history of inflammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM: To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD. METHODS: An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. RESULTS: 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION: The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.

Propuesta para la creación de una Estrategia Nacional sobre Medicina de Precisión en Cáncer: posicionamiento de la SEOM, SEAP y SEFH / Proposal of the SEOM, SEAP and SEFH for the creation of a National Strategy for Precision Medicine in Cancer

La medicina de precisión es un enfoque emergente para el tratamiento y prevención de las enfermedades que tiene en cuenta la variabilidad individual en los genes, el medio ambiente y el estilo de vida de cada persona. La medicina de precisión está transformando la investigación clínica y biomédica así como la asistencia sanitaria, tanto desde un punto de vista conceptual como metodológico, ofertando oportunidades extraordinarias para mejorar la salud pública y reducir los costes del sistema sanitario. Sin embargo, la implementación de la medicina de precisión supone un reto a nivel ético-legal, regulatorio, organizativo y de conocimiento. Sin una estrategia nacional, la medicina de precisión, que se implantará en cualquier caso, lo podría hacer sin la adecuada planificación que permita garantizar la calidad técnica, la equidad de los ciudadanos en el acceso a las mejores prácticas, vulnerando los derechos de pacientes y profesionales y arriesgando la solvencia del sistema de salud. Con este artículo de las sociedades españolas de Oncología Médica (SEOM), Anatomía Patológica (SEAP) y Farmacia Hospitalaria (SEFH), señalamos la necesidad de establecer una estrategia nacional consensuada para el desarrollo de la medicina de precisión en nuestro país, revisamos el contexto nacional e internacional, comentamos las oportunidades y los retos para la implementación de la medicina de precisión, y delineamos los objetivos de una estrategia nacional sobre medicina de precisión en cáncer

Precision medicine is an emerging approach to the prevention and treatment of disease that takes into account variability in genes, environment and lifestyle for each individual. Precision medicine is transforming clinical and biomedical research, as well as health care itself, from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges. Without a national strategy, precision medicine -which eventually will be implemented one way or another- could take place without the appropriate planning to guarantee technical quality and equal access to the best practices for all citizens, thus violating the rights of patients and professionals as well as jeopardizing the solvency of the healthcare system. This paper from the Spanish Societies of Medical Oncology (SEOM), Pathology (SEAP) and Hospital Pharmacy (SEFH), highlights the need to institute a consensual national strategy for the development of precision medicine in our country, reviews the national and international context, comments on the opportunities and challenges for implementing precision medicine and outlines the objectives of a national strategy on precision medicine in cancer

[Proposal of the SEOM, SEAP and SEFH for the creation of a National Strategy for Precision Medicine in Cancer]. / Propuesta para la creación de una Estrategia Nacional sobre Medicina de Precisión en Cáncer: posicionamiento de la SEOM, SEAP y SEFH.

Precision medicine is an emerging approach to the prevention and treatment of disease that takes into account variability in genes, environment and lifestyle for each individual. Precision medicine is transforming clinical and biomedical research, as well as health care itself, from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges. Without a national strategy, precision medicine -which eventually will be implemented one way or another- could take place without the appropriate planning to guarantee technical quality and equal access to the best practices for all citizens, thus violating the rights of patients and professionals as well as jeopardizing the solvency of the healthcare system. This paper from the Spanish Societies of Medical Oncology (SEOM), Pathology (SEAP) and Hospital Pharmacy (SEFH), highlights the need to institute a consensual national strategy for the development of precision medicine in our country, reviews the national and international context, comments on the opportunities and challenges for implementing precision medicine and outlines the objectives of a national strategy on precision medicine in cancer.

Defining a set of standardised outcome measures for newly diagnosed patients with multiple myeloma using the Delphi consensus method: the IMPORTA project.

OBJECTIVE: To define a standard set of outcomes and the most appropriate instruments to measure them for managing newly diagnosed patients with multiple myeloma (MM). METHODS: A literature review and five discussion groups facilitated the design of two-round Delphi questionnaire. Delphi panellists (haematologists, hospital pharmacists and patients) were identified by the scientific committee, the Spanish Program of Haematology Treatments Foundation, the Spanish Society of Hospital Pharmacies and the Spanish Community of Patients with MM. Panellist's perception about outcomes' suitability and feasibility of use was assessed on a seven-point Likert scale. Consensus was reached when at least 75% of the respondents reached agreement or disagreement. A scientific committee led the project. RESULTS: Fifty-one and 45 panellists participated in the first and second Delphi rounds, respectively. Consensus was reached to use overall survival, progression-free survival, minimal residual disease and treatment response to assess survival and disease control. Panellists agreed to measure health-related quality of life, pain, performance status, fatigue, psychosocial status, symptoms, self-perception on body image, sexuality and preferences/satisfaction. However, panellist did not reach consensus about the feasibility of assessing in routine practice psychosocial status, symptoms, self-perception on body image and sexuality. Consensus was reached to collect patient-reported outcomes through the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core questionnaire 30 (C30), three items from EORTC-QLQ-Multiple Myeloma (MY20) and EORTC-QLQ-Breast Cancer (BR23), pain Visual Analogue Scale, Morisky-Green and ad hoc questions about patients' preferences/satisfaction. CONCLUSIONS: A consensual standard set of outcomes for managing newly diagnosed patients with MM has been defined. The feasibility of its implementation in routine practice will be assessed in a future pilot study.

Propuesta para la creación de una Estrategia Nacional sobre Medicina de Precisión en Cáncer: posicionamiento de la SEOM, SEAP y SEFH / Proposal for the Creation of a National Strategy for Precision Medicine in Cancer: a position statement of SEOM, SEAP and SEFH

La medicina de precisión es un enfoque emergente para el tratamiento y prevención de las enfermedades que tiene en cuenta la variabilidad individual en los genes, el medio ambiente y el estilo de vida de cada persona. La medicina de precisión está transformando la investigación clínica y biomédica así como la asistencia sanitaria, tanto desde un punto de vista conceptual como metodológico, ofertando oportunidades extraordinarias para mejorar la salud pública y reducir los costes del sistema sanitario. Sin embargo, la implementación de la medicina de precisión supone un reto a nivel ético-legal, regulatorio, organizativo y de conocimiento. Sin una estrategia nacional, la medicina de precisión, que se implantará en cualquier caso, lo podría hacer sin la adecuada planificación que permita garantizar la calidad técnica, la equidad de los ciudadanos en el acceso a las mejores prácticas, vulnerando los derechos de pacientes y profesionales y arriesgando la solvencia del sistema de salud. Con este artículo de las sociedades españolas de Oncología Médica (SEOM), Anatomía Patológica (SEAP) y Farmacia Hospitalaria (SEFH) señalamos la necesidad de establecer una estrategia nacional consensuada para el desarrollo de la medicina de precisión en nuestro país, revisamos el contexto nacional e internacional, comentamos las oportunidades y los retos para la implementación de la medicina de precisión, y delineamos los objetivos de una estrategia nacional sobre medicina de precisión en el cáncer (AU)

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology (SEOM), Pathology (SEAP), and Hospital Pharmacy (SEFH) we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cáncer (AU)

Proposal for the Creation of a National Strategy for Precision Medicine in Cancer: a position statement of SEOM, SEAP and SEFH.

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology (SEOM), Pathology (SEAP), and Hospital Pharmacy (SEFH) we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer.

La medicina de precisión es un enfoque emergente para el tratamiento y prevención de las enfermedades que tiene en cuenta la variabilidad individual en los genes, el medio ambiente y el estilo de vida de cada persona. La medicina de precisión está transformando la investigación clínica y biomédica así como la asistencia sanitaria, tanto desde un punto de vista conceptual como metodológico, ofertando oportunidades extraordinarias para mejorar la salud pública y reducir los costes del sistema sanitario. Sin embargo, la implementación de la medicina de precisión supone un reto a nivel ético-legal, regulatorio, organizativo y de conocimiento. Sin una estrategia nacional, la medicina de precisión, que se implantará en cualquier caso, lo podría hacer sin la adecuada planificación que permita garantizar la calidad técnica, la equidad de los ciudadanos en el acceso a las mejores prácticas, vulnerando los derechos de pacientes y profesionales y arriesgando la solvencia del sistema de salud. Con este artículo de las sociedades españolas de Oncología Médica (SEOM), Anatomía Patológica (SEAP) y Farmacia Hospitalaria (SEFH) señalamos la necesidad de establecer una estrategia nacional consensuada para el desarrollo de la medicina de precisión en nuestro país, revisamos el contexto nacional e internacional, comentamos las oportunidades y los retos para la implementación de la medicina de precisión, y delineamos los objetivos de una estrategia nacional sobre medicina de precisión en el cáncer.

Liquid chromatography tandem mass spectrometric determination of triterpenes in human fluids: Evaluation of markers of dietary intake of olive oil and metabolic disposition of oleanolic acid and maslinic acid in humans.

Olive oil is rich in several minor components like maslinic (MA) and oleanolic (OA) acids which have cardioprotective, antitumor, and anti-inflammatory properties. In order to assess the health benefits in humans provided by the olive oil triterpenes (MA and OA), suitable analytical methods able to quantify the low concentrations expected in human fluids are required. In this study, the LC-MS/MS quantification of both OA and MA in plasma and urine has been evaluated. The plasmatic method is based on the direct determination of the analytes. The urinary detection requires more sensitivity which was reached by derivatization with 2-picolylamine. Additionally, the urinary species present after MA and OA ingestion were evaluated by the direct detection of several phase II metabolites previously synthesized. Our results showed that OA is metabolized as both sulfate and glucuronide conjugates whereas MA is mainly excreted as glucuronide. Based on this information, the method for the urinary detection of MA and OA involved an enzymatic hydrolysis. Both plasmatic and urinary methods were validated with suitable precision and accuracy at all tested levels. Required sensitivity was achieved in both matrices. Up to our knowledge, this is the first method able to quantify the low concentration levels of triterpenes present in urine. Samples from two healthy volunteers who received virgin olive oils with different triterpenes content were analyzed. Some preliminary clues on the metabolic disposition of OA and MA after olive oil intake are provided.

The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils.

BACKGROUND: Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO). METHODS/DESIGN: A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion. DISCUSSION: For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition. TRIAL REGISTRATION: The Trial has been registered in ClinicalTrials.gov ID: NCT02520739 .