Strategies to decrease inequalities in cancer therapeutics, care and prevention: Proceedings on a conference organized by the Pontifical Academy of Sciences and the European Academy of Cancer Sciences, Vatican City, February 23-24, 2023.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare.

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.

An experience- and preference-based EQ-5D-3L value set derived using 18 months of longitudinal data in patients who sustained a fracture: results from the ICUROS.

INTRODUCTION: EQ-5D-3L preference-based value sets are predominately based on hypothetical health states and derived in cross-sectional settings. Therefore, we derived an experience-based value set from a prospective observational study. METHODS: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) was a multinational study on fragility fractures, prospectively collecting EQ-5D-3L and Time trade-off (TTO) within two weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months thereafter. We derived an EQ-5D-3L value set by regressing the TTO values on the ten impairment levels in the EQ-5D-3L. We explored the potential for response shift and whether preferences for domains vary systematically with prior impairment in that domain. Finally, we compared the value set to 25 other EQ-5D-3L preference-based value sets. RESULTS: TTO data were available for 12,954 EQ-5D-3L health states in 4683 patients. All coefficients in the value set had the expected sign, were statistically significant, and increased monotonically with severity of impairment. We found evidence for response shift in mobility, self-care, and usual activities. The value set had good agreement with the only other experience- and preference-based value set, but poor agreement with all hypothetical value sets. CONCLUSIONS: We present an experience- and preference-based value set with high face validity. The study indicates that response shift may be important to account for when deriving value sets. Furthermore, the study suggests that perspective (experienced versus hypothetical) is more important than country setting or demographics for valuation of EQ-5D-3L health states.

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.

How to improve efficiency in cancer care: Dimensions, methods, and areas of evaluation.

Efficiency in healthcare is crucial since available resources are scarce, and the cost of inefficient allocation is measured in prior outcomes. This is particularly relevant for cancer. The aim of this paper is to gain a comprehensive overview of the areas and dimensions to improve efficiency, and establish the indicators, different methods, perspectives, and areas of evaluation, to provide recommendations for how to improve efficiency and measure gains in cancer care. METHODS: We conducted a two-phase design. First, a comprehensive scoping literature review was conducted, searching four databases. Studies published between 2000 and 2021 were included if they described experiences and cases of efficiency in cancer care or methods to evaluate efficiency. The results of the literature review were then discussed during two rounds of online consultation with a panel of 15 external experts invited to provide insight and comments to deliberate policy recommendations. RESULTS: 46 papers met the inclusion criteria. Based on the papers retrieved we identified six areas for achieving efficiency gains throughout the entire care pathway and, for each area of efficiency, we categorized the methods and outcomes used to measure efficiency gain. CONCLUSION: This is the first attempt to systemize a scattered body of literature on how to improve efficiency in cancer care and identify key areas of improvement. POLICY SUMMARY: There are many opportunities to improve efficiency in cancer care. We defined seven policy recommendations on how to improve efficiency in cancer care throughout the care pathway and how to improve the measurement of efficiency gains.

Multiple drivers of large-scale lichen decline in boreal forest canopies.

Thin, hair-like lichens (Alectoria, Bryoria, Usnea) form conspicuous epiphyte communities across the boreal biome. These poikilohydric organisms provide important ecosystem functions and are useful indicators of global change. We analyse how environmental drivers influence changes in occurrence and length of these lichens on Norway spruce (Picea abies) over 10 years in managed forests in Sweden using data from >6000 trees. Alectoria and Usnea showed strong declines in southern-central regions, whereas Bryoria declined in northern regions. Overall, relative loss rates across the country ranged from 1.7% per year in Alectoria to 0.5% in Bryoria. These losses contrasted with increased length of Bryoria and Usnea in some regions. Occurrence trajectories (extinction, colonization, presence, absence) on remeasured trees correlated best with temperature, rain, nitrogen deposition, and stand age in multinomial logistic regression models. Our analysis strongly suggests that industrial forestry, in combination with nitrogen, is the main driver of lichen declines. Logging of forests with long continuity of tree cover, short rotation cycles, substrate limitation and low light in dense forests are harmful for lichens. Nitrogen deposition has decreased but is apparently still sufficiently high to prevent recovery. Warming correlated with occurrence trajectories of Alectoria and Bryoria, likely by altering hydration regimes and increasing respiration during autumn/winter. The large-scale lichen decline on an important host has cascading effects on biodiversity and function of boreal forest canopies. Forest management must apply a broad spectrum of methods, including uneven-aged continuous cover forestry and retention of large patches, to secure the ecosystem functions of these important canopy components under future climates. Our findings highlight interactions among drivers of lichen decline (forestry, nitrogen, climate), functional traits (dispersal, lichen colour, sensitivity to nitrogen, water storage), and population processes (extinction/colonization).

Value appropriation in hepatitis C.

BACKGROUND: In 2015, the Swedish government in an unprecedented move decided to allocate 150 million € to provide funding for new drugs for hepatitis C. This was triggered by the introduction of the first second generation of direct-acting antivirals (DAAs) promising higher cure rates and reduced side effects. The drugs were cost-effective but had a prohibitive budget impact. Subsequently, additional products have entered the market leading to reduction in prices and expansions of the eligible patient base. METHODS: We estimated the social surplus generated by the new DAAs in Stockholm, Sweden, for the years 2014-2019. The actual use and cost of the drugs was based on registry data. Effects on future health care costs, indirect costs and QALY gains were estimated using a Markov model based primarily on Swedish data and using previous generations of interferon-based therapies as the counterfactual. RESULTS: A considerable social surplus was generated, 15% of which was appropriated by the producers whose share fell rapidly over time as prices fell. Most of the consumer surplus was generated by QALY gains, although 10% was from reduced indirect costs. QALY gains increased less rapidly than the number of treated patients as the eligibility criteria was loosened. CONCLUSIONS: The transfer of funds from the government to the regions helped generate substantial surplus for both consumers and producers with indirect costs playing an important role. The funding model may serve as a model for the financing of innovative treatments in the future.

The Porto European Cancer Research Summit 2021.

Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high-quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures - namely translational research, clinical/prevention trials and outcomes research - were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next-generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health-related quality-of-life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU-wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost.

Perspectives on the Classical Enzyme Carbonic Anhydrase and the Search for Inhibitors.

Carbonic anhydrase (CA) is a thoroughly studied enzyme. Its primary role is the rapid interconversion of carbon dioxide and bicarbonate in the cells, where carbon dioxide is produced, and in the lungs, where it is released from the blood. At the same time, it regulates pH homeostasis. The inhibitory function of sulfonamides on CA was discovered some 80 years ago. There are numerous physiological-therapeutic conditions in which inhibitors of carbonic anhydrase have a positive effect, such as glaucoma, or act as diuretics. With the realization that several isoenzymes of carbonic anhydrase are associated with the development of several types of cancer, such as brain and breast cancer, the development of inhibitor drugs specific to those enzyme forms has exploded. We would like to highlight the breadth of research on the enzyme as well as draw the attention to some problems in recent published work on inhibitor discovery.

Propelling Health Care into the Twenties.

The scope and potential of personalised health care are underappreciated and underrealised, often because of resistance to change. The consequence is that many inadequacies of health care in Europe persist unnecessarily, and many opportunities for improvement are neglected. This article identifies the principal challenges, outlines possible approaches to resolving them, and highlights the benefits that could result from greater adoption of personalised health care. It locates the discussion in the context of European policy, focusing particularly on the most recent and authoritative reviews of health care in the EU Member States, and on the newly acquired spirit of readiness and pragmatism among European officials to embrace change and innovative technologies in a new decade. It highlights the attention now being given by policymakers to incentives, innovation, and investment as levers to improve European citizens' prospects in a rapidly evolving world, and how these distinct and disruptive themes contribute to a renaissance in thinking about delivering optimal health care in Europe. It explores the chances offered to patients by specific initiatives in health domains such as cancer and antimicrobial resistance, and by innovative science, novel therapies, earlier diagnosis tools, and deeper understanding of health promotion and prevention. And it reflects on how health care providers could benefit from a shift towards better primary care and towards deploying health data more effectively, including the use of artificial intelligence, coupled with a move to a smoother organisational/regulatory structure and realigned professional responsibilities. The conclusion is that preparing Europe's health care systems for the inevitable strains of the coming years is both possible and necessary. A more courageous approach to embracing personalised health care could guarantee the sustainability of Europe's health care systems before rising demands and exponential costs overwhelm them - an exercise in future-proofing, in ensuring that they are equipped to withstand whatever lies ahead. A focus on the potential and implementation of personalised care would permit more efficient use of resources and deliver better quality health-preserving care.

Cost of non-alcoholic steatohepatitis in Europe and the USA: The GAIN study.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) leads to cirrhosis and is associated with a substantial socioeconomic burden, which, coupled with rising prevalence, is a growing public health challenge. However, there are few real-world data available describing the impact of NASH. METHODS: The Global Assessment of the Impact of NASH (GAIN) study is a prevalence-based burden of illness study across Europe (France, Germany, Italy, Spain, and the UK) and the USA. Physicians provided demographic, clinical, and economic patient information via an online survey. In total, 3,754 patients found to have NASH on liver biopsy were stratified by fibrosis score and by biomarkers as either early or advanced fibrosis. Per-patient costs were estimated using national unit price data and extrapolated to the population level to calculate the economic burden. Of the patients, 767 (20%) provided information on indirect costs and health-related quality of life using the EuroQOL 5-D (EQ-5D; n = 749) and Chronic Liver Disease Questionnaire - Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) (n = 723). RESULTS: Mean EQ-5D and CLDQ-NAFLD index scores were 0.75 and 4.9, respectively. For 2018, the mean total annual per patient cost of NASH was €2,763, €4,917, and €5,509 for direct medical, direct non-medical, and indirect costs, respectively. National per-patient cost was highest in the USA and lowest in France. Costs increased with fibrosis and decompensation, driven by hospitalisation and comorbidities. Indirect costs were driven by work loss. CONCLUSIONS: The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in Europe and the USA, showing a substantial burden on health services and individuals. LAY SUMMARY: There has been little research into the socioeconomic burden associated with non-alcoholic steatohepatitis (NASH). The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in five European countries (UK, France, Germany, Spain, and Italy) and the USA. Mean total annual per patient cost of NASH was estimated at €2,763, €4,917, and €5,509 for the direct medical, direct non-medical, and indirect cost categories, respectively.

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.

The cost of cancer in Europe 2018.

BACKGROUND: Cancer care is evolving rapidly, and costs and value of new treatments are frequently debated. Up-to-date evidence on the total cost of cancer is needed to inform policy decisions. This study estimates the cost of cancer in Europe in 2018 and extends a previous analysis for 1995-2014. METHODS: Cancer-specific health expenditure were derived from national estimates. Data on cancer drug sales were obtained from IQVIA. The productivity loss from premature mortality was estimated from data from Eurostat and the World Health Organization. Estimates of the productivity loss from morbidity and informal care costs were based on previous studies. FINDINGS: The total cost of cancer was €199 billion in Europe (EU-27 plus Iceland, Norway, Switzerland, and the United Kingdom) in 2018. Total costs ranged from €160 per capita in Romania to €578 in Switzerland (after adjustment for price differentials). Health expenditure on cancer care were €103 billion, of which €32 billion were spent on cancer drugs. Informal care costs were €26 billion. The total productivity loss was €70 billion, composed of €50 billion from premature mortality and €20 billion from morbidity. INTERPRETATION: Health expenditure on cancer care were of a similar magnitude as the sum of non-health-care costs in 2018. Over the last two decades, health spending on cancer has increased faster than the increase in cancer incidence. The productivity loss from premature mortality has decreased because of reductions in mortality in the working-age population. Trends in informal care costs and productivity loss from morbidity are uncertain because of lack of comparable data.

Mission-oriented translational cancer research - health economics.

Health economics is an integrated aspect of all phases of mission-oriented translational cancer research and should be considered an intrinsic component of any study aimed at improving outcomes for patients and intervention costs. Information about value and value for money of new options for prevention and treatment is needed for decisions about their adoption and use by healthcare systems.

Landscape trajectory of natural boreal forest loss as an impediment to green infrastructure.

Loss of natural forests by forest clearcutting has been identified as a critical conservation challenge worldwide. This study addressed forest fragmentation and loss in the context of the establishment of a functional green infrastructure as a spatiotemporally connected landscape-scale network of habitats enhancing biodiversity, favorable conservation status, and ecosystem services. Through retrospective analysis of satellite images, we assessed a 50- to 60-year spatiotemporal clearcutting impact trajectory on natural and near-natural boreal forests across a sizable and representative region from the Gulf of Bothnia to the Scandinavian Mountain Range in northern Fennoscandia. This period broadly covers the whole forest clearcutting period; thus, our approach and results can be applied to comprehensive impact assessment of industrial forest management. The entire study region covers close to 46,000 km2 of forest-dominated landscape in a late phase of transition from a natural or near-natural to a land-use modified state. We found a substantial loss of intact forest, in particular of large, contiguous areas, a spatial polarization of remaining forest on regional scale where the inland has been more severely affected than the mountain and coastal zones, and a pronounced impact on interior forest core areas. Salient results were a decrease in area of the largest intact forest patch from 225,853 to 68,714 ha in the mountain zone and from 257,715 to 38,668 ha in the foothills zone, a decrease from 75% to 38% intact forest in the inland zones, a decrease in largest patch core area (assessed by considering 100-m patch edge disturbance) from 6114 to 351 ha in the coastal zone, and a geographic imbalance in protected forest with an evident predominance in the mountain zone. These results demonstrate profound disturbance of configuration of the natural forest landscape and disrupted connectivity, which challenges the establishment of functional green infrastructure. Our approach supports the identification of forests for expanded protection and conservation-oriented forest landscape restoration.

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare.

BACKGROUND: Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. OBJECTIVES: To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology-specifically economic evaluation methods-in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. METHODS: An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. RESULTS: Three key topics were identified and prioritised for discussion-uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. CONCLUSIONS: ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. CLASSIFICATION CODE: I.

Cost of Cancer: Healthcare Expenditures and Economic Impact.

Healthcare expenditures for cancer account for a low share of total healthcare expenditures, compared to the relative burden of the disease. The share has also not changed very much over the last decades. Cost for cancer drugs has increased as a share of total expenditures, but this has been offset by a reduction of inpatient hospital care for cancer. Accounting for the cost of cancer should not be limited to healthcare expenditures. Resources are also used for public and private care of cancer patients outside the healthcare sector, for example for palliative care. Informal care by family and friends is an important complement to professional care, and estimates indicate that this amounts to between half and one-third of the costs of formal care. Indirect costs related to the loss of production for persons with cancer are estimated to be of the same magnitude as the direct healthcare expenditures. Indirect costs related to premature mortality dominate the estimate of indirect costs, but those costs have declined over time, despite increasing incomes, due to the reduction in mortality due to cancer in the economically active age groups. Estimates of indirect costs due to morbidity are uncertain and vary significantly between published studies. A full accounting of the costs of cancer should include an estimate of the health burden of cancer. Loss of quality-adjusted life expectancy (QALY) can be measured and valued based on the willingness to pay for a QALY. Such estimates are possible to derive from decisions about allocating resources for cancer. There are few estimates of these costs, but available studies indicate that the intangible costs of lost QALY are by far the dominating cost of cancer. The value for policy-making of costs of cancer estimates increases when results with consistent methods and data are available that allow comparisons between countries and over time. The evidence about the cost of cancer is still limited, but when current scientific progress produces an increasing number of new options for prevention, diagnosis and treatment, studies of the cost of cancer become increasingly important to inform decisions about resource allocation.