Revised European Association for Palliative Care (EAPC) recommended framework on palliative sedation: An international Delphi study.

BACKGROUND: The European Association for Palliative Care (EAPC) acknowledges palliative sedation as an important, broadly accepted intervention for patients with life-limiting disease experiencing refractory symptoms. The EAPC therefore developed 2009 a framework on palliative sedation. A revision was needed due to new evidence from literature, ongoing debate and criticism of methodology, terminology and applicability. AIM: To provide evidence- and consensus-based guidance on palliative sedation for healthcare professionals involved in end-of-life care, for medical associations and health policy decision-makers. DESIGN: Revision between June 2020 and September 2022 of the 2009 framework using a literature update and a Delphi procedure. SETTING: European. PARTICIPANTS: International experts on palliative sedation (identified through literature search and nomination by national palliative care associations) and a European patient organisation. RESULTS: A framework with 42 statements for which high or very high level of consensus was reached. Terminology is defined more precisely with the terms suffering used to encompass distressing physical and psychological symptoms as well as existential suffering and refractory to describe the untreatable (healthcare professionals) and intolerable (patient) nature of the suffering. The principle of proportionality is introduced in the definition of palliative sedation. No specific period of remaining life expectancy is defined, based on the principles of refractoriness of suffering, proportionality and independent decision-making for hydration. Patient autonomy is emphasised. A stepwise pharmacological approach and a guidance on hydration decision-making are provided. CONCLUSIONS: This is the first framework on palliative sedation using a strict consensus methodology. It should serve as comprehensive and soundly developed information for healthcare professionals.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Access and quality of biomarker testing for precision oncology in Europe.

BACKGROUND: Predictive biomarkers are essential for selecting the best therapeutic strategy in patients with cancer. The International Quality Network for Pathology, the European Cancer Patient Coalition and the European Federation of Pharmaceuticals Industries and Associations evaluated the access to and quality of biomarker testing across Europe. METHODS: Data sources included surveys of 141 laboratory managers and 1.665 patients, and 58 in-depth interviews with laboratory managers, physicians and payers. Four access metrics (laboratory access, test availability, test reimbursement, test order rate) and three quality metrics (quality scheme participation, laboratory accreditation, test turnaround time) were applied to rank the results. RESULTS: The access to precision medicines is higher in countries with public national reimbursement processes in place. Lack of diagnostic laboratory infrastructure, inefficient organization and/or insufficient public reimbursement narrow the access to single biomarker tests in many European countries. In countries with limited public reimbursement, pharma and patients' out of pocket were the primary funding sources for testing. Uptake of multi-biomarker next generation sequencing (NGS) is highly varied, ranging from 0% to >50%. Financial constraints, a lack of NGS testing capabilities and the failure to include NGS testing in the guidelines represent the main barriers to NGS implementation. The quality of biomarker testing is highest in Western and Northern Europe, with more than 90% of laboratories participating in quality assurance schemes. CONCLUSIONS: Our data clearly indicate the need for a call to action to ensure the clinical implementation of precision medicine in Europe.

Towards Better Pharmaceutical Provision in Europe-Who Decides the Future?

Significant progress has been achieved in human health in the European Union in recent years. New medicines, vaccines, and treatments have been developed to tackle some of the leading causes of disease and life-threatening illnesses. It is clear that investment in research and development (R&D) for innovative medicines and treatments is essential for making progress in preventing and treating diseases. Ahead of the legislative process, which should begin by the end of 2022, discussions focus on how Europe can best promote the huge potential benefits of new science and technology within the regulatory framework. The challenges in European healthcare were spelled out by the panellists at the roundtable organised by European Alliance for Personalised Medicine (EAPM). Outcomes from panellists' discussions have been summarized and re-arranged in this paper under five headings: innovation, unmet medical need, access, security of supply, adapting to progress, and efficiency. Some of the conclusions that emerged from the panel are a call for a better overall holistic vision of the future of pharmaceuticals and health in Europe and a collaborative effort among all stakeholders, seeing the delivery of medicines as part of a broader picture of healthcare.

Cancer Biomarkers in the era of precision oncology: Addressing the needs of patients and health systems.

Cancer Biomarkers are the key to unlocking the promise of precision oncology, selecting which patients will respond to a more personalised treatment while sparing non-responders the therapy-related toxicity. In this paper, we highlight the primacy of cancer biomarkers, but focus on their importance to patients and to health systems. We also highlight how cancer biomarkers represent value for money. We emphasise the need for cancer biomarkers infrastructure to be embedded into European health systems. We also highlight the need to deploy multiple biomarker testing to deliver the optimal benefit for patients and health systems and consider cancer biomarkers from the perspective of cost, value and regulation. Cancer biomarkers must also be situated in the context of the upcoming In Vitro Diagnostics Regulation, which may pose certain challenges (e.g. non-compliance of laboratory developed tests, leading to cancer biomarker shortages and increased costs) that need to be overcome. Cancer biomarkers must be embedded in the real world of oncology delivery and testing must be implemented across Europe, with the intended aim of narrowing, not widening the inequity gap for patients. Cancer patients must be placed firmly at the centre of a cancer biomarker informed precision oncology care agenda.

Towards a cancer mission in Horizon Europe: recommendations.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice.

Behind the numbers and the panic of a viral pandemic: fixed restrictive oncology guidance may jeopardize patients' survival.

To protect cancer patients from COVID-19 exposure, prioritization strategies are being implemented at global level. Measures include use of tele-health services, deferring elective surgeries, delaying non life-saving therapies, interrupting maintenance and supportive care regimens and suspending screening and regular follow-up visits. Nonetheless, the risk of infection may not always outweigh oncology treatment benefit. Lives of most oncology patients depend on their ability to receive medical, surgical and radiotherapy care. Postponing screening, follow-up and radical surgeries increase patients' risk of developing metastatic disease. A viral pandemic lasts long time and exhibits seasonal and geographical variations. Though vaccines will be available only in the 2021, a global, aggressive, all-embracing and protracted slowdown of oncologic activities will severely jeopardize patients' outcomes. A present international oncologists' panel, ECPC and FAVO, strongly suggest that Hospital measures in a specific geographical area/Nation should be in line with the local epidemic, and restrictions adopted should be adapted and stratified over time.

What could be a cancer mission objective if we join our forces in the fight against cancer?

The European cancer burden is growing rapidly, with an estimated 2 million deaths a year according to the latest research. As almost half of cancers are diagnosed after the age of 65, and considering the aging European population, a tidal wave of cancer cases will sweep across Europe within the coming decades. Without major action, the additional number of annual cancer cases is expected to rise from 4.2 million to 5.2 million by 2040. If we are to reach plateauing numbers by 2040 (as a minimum goal), this would require 0.75% annual reduction in risk and 1% reduction in risk of death. These challenges call for attack from various angles, coordinated efforts, rational strategies, initiatives throughout the cancer trajectory, activities to reduce inequities, and implementation of evidence-based measures. In order to defeat the societal challenges of cancer through innovation, Europe will need to join forces and connect the European Commission and the member states, politicians and citizens, industries and patient associations. A cancer mission should thus unite the public and patient viewpoint to the perspective of cancer professionals. The authors describe a plan that has been agreed upon among some of the major European Cancer organizations and associations. This plan uses a cancer mission as a tool and must deliver robust medical evidence to patients and doctors through high-quality research delivering sustainable and affordable strategies for prevention, treatment, and follow-up.

The ENCePP Code of Conduct: A best practise for scientific independence and transparency in noninterventional postauthorisation studies.

PURPOSE: The ENCePP Code of Conduct provides a framework for scientifically independent and transparent pharmacoepidemiological research. Despite becoming a landmark reference, practical implementation of key provisions was still limited. The fourth revision defines scientific independence and clarifies uncertainties on the applicability to postauthorisation safety studies requested by regulators. To separate the influence of the funder from the investigator's scientific responsibility, the Code now requires that the lead investigator is not employed by the funding institution. METHOD: To assess how the revised Code fits the ecosystem of noninterventional pharmacoepidemiology research in Europe, we first mapped key recommendations of the revised Code against ISPE Good Pharmacoepidemiology Practices and the ADVANCE Code of Conduct. We surveyed stakeholders to understand perceptions on its value and practical applicability. Representatives from the different stakeholders' groups described their experience and expectations. RESULTS: Unmet needs in pharmacoepidemiological research are fulfilled by providing unique guidance on roles and responsibilities to support scientific independence. The principles of scientific independence and transparency are well understood and reinforce trust in study results; however, around 70% of survey respondents still found some provisions difficult to apply. Representatives from stakeholders' groups found the new version promising, although limitations still exist. CONCLUSION: By clarifying definitions and roles, the latest revision of the Code sets a new standard in the relationship between investigators and funders to support scientific independence of pharmacoepidemiological research. Disseminating and training on the provisions of the Code would help stakeholders to better understand its advantages and promote its adoption in noninterventional research.

The European Cancer Patient Coalition and its central role in connecting stakeholders to advance patient-centric solutions in the mission on cancer.

There is an urgent need for solutions to the economic and social inequalities in cancer care that still exist in many European countries. Patient preferences, 'big data', mobile digital technology and molecular and genomic profiling are among the innovative research topics that connect cancer patients to comprehensive cancer centres, and link translational research to cancer diagnosis, treatment and care. The question is whether Europe can deliver the complex infrastructure needed for universal coverage and equitable access to cancer care. The European Cancer Patient Coalition (ECPC), the leading 'umbrella' cancer patient organisation in Europe, has a central role in bringing the unmet needs of patients with cancer to the forefront of cancer policy, care and research. The ECPC is a respected and reliable partner in the oncology community and has effectively collaborated with institutional stakeholders and organisations, as well as with the European Commission, on cancer research projects and in the development of tools to advance health care and cancer policies at the European and national level. The ECPC believes that innovation cannot emerge and grow without patient involvement and is fully committed to increasing patient education and contribution in cancer research through its active participation in various European cancer research programmes and educational resources. The ECPC is expected to play a major role in the mission on cancer, given its previous achievements in policy and research to help overcome the inequalities in cancer prevention, treatment, rehabilitation and survivorship care. The mission on cancer will be facilitated by active collaboration between patient organisations and scientists, clinicians, politicians and industry, with the aim of identifying important research questions regarding quality of life and social issues for cancer patients of all ages.

Congruence Between Latent Class and K-Modes Analyses in the Identification of Oncology Patients With Distinct Symptom Experiences.

CONTEXT: Risk profiling of oncology patients based on their symptom experience assists clinicians to provide more personalized symptom management interventions. Recent findings suggest that oncology patients with distinct symptom profiles can be identified using a variety of analytic methods. OBJECTIVES: The objective of this study was to evaluate the concordance between the number and types of subgroups of patients with distinct symptom profiles using latent class analysis and K-modes analysis. METHODS: Using data on the occurrence of 25 symptoms from the Memorial Symptom Assessment Scale, that 1329 patients completed prior to their next dose of chemotherapy (CTX), Cohen's kappa coefficient was used to evaluate for concordance between the two analytic methods. For both latent class analysis and K-modes, differences among the subgroups in demographic, clinical, and symptom characteristics, as well as quality of life outcomes were determined using parametric and nonparametric statistics. RESULTS: Using both analytic methods, four subgroups of patients with distinct symptom profiles were identified (i.e., all low, moderate physical and lower psychological, moderate physical and higher Psychological, and all high). The percent agreement between the two methods was 75.32%, which suggests a moderate level of agreement. In both analyses, patients in the all high group were significantly younger and had a higher comorbidity profile, worse Memorial Symptom Assessment Scale subscale scores, and poorer QOL outcomes. CONCLUSION: Both analytic methods can be used to identify subgroups of oncology patients with distinct symptom profiles. Additional research is needed to determine which analytic methods and which dimension of the symptom experience provide the most sensitive and specific risk profiles.

Learning from data to predict future symptoms of oncology patients.

Effective symptom management is a critical component of cancer treatment. Computational tools that predict the course and severity of these symptoms have the potential to assist oncology clinicians to personalize the patient's treatment regimen more efficiently and provide more aggressive and timely interventions. Three common and inter-related symptoms in cancer patients are depression, anxiety, and sleep disturbance. In this paper, we elaborate on the efficiency of Support Vector Regression (SVR) and Non-linear Canonical Correlation Analysis by Neural Networks (n-CCA) to predict the severity of the aforementioned symptoms between two different time points during a cycle of chemotherapy (CTX). Our results demonstrate that these two methods produced equivalent results for all three symptoms. These types of predictive models can be used to identify high risk patients, educate patients about their symptom experience, and improve the timing of pre-emptive and personalized symptom management interventions.

The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer.

INTRODUCTION: While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients. METHODS AND ANALYSIS: A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes). ETHICS AND DISSEMINATION: Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts. TRIAL REGISTRATION NUMBER: NCT02356081.