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.

Propelling Healthcare with Advanced Therapy Medicinal Products: A Policy Discussion.

Recent advances in biomedicine are opening the door to new approaches, and treatment and prevention are being transformed by novel medicines based on genetic engineering, innovative cell-based therapies and tissue-engineered products, and combinations of a medical device with embedded cell or tissue components. These advanced therapy medicinal products (ATMPs) hold one of the keys to making a reality of genuinely personalised medicine. There are an estimated 450 companies across the globe working on the development of gene therapies and more than 1,000 clinical trials underway worldwide, and some 20-30 new ATMPs filings are expected in Europe annually over the next 5 years. But challenges confront the sector, complicating the translation from research into patient access. Scientific, clinical development and regulatory issues are compounded by limited experience with clinical and commercial use, limited manufacturing know-how, high costs, and difficulties in accessing development funding and investment. Pricing and reimbursement and market access issues are an additional challenge, particularly in Europe, where unfamiliarity with the technology and uncertainty over the use of real-world evidence induce caution among clinicians, health technology assessment bodies and payers. There is a need for a review of the suitability of the regulatory and market access framework for these products, focused development of data, public/private partnerships, and fuller collaboration governments, doctors, insurers, patients, and pharmaceutical companies. This paper makes specific recommendations for all stakeholders, ranging from early dialogue on potential products, linking of clinical data and patient registries or standardisation of control frameworks, to a comprehensive approach to evidence generation, assessment, pricing, and payment for ATMPs.

BBMRI-ERIC as a resource for pharmaceutical and life science industries: the development of biobank-based Expert Centres.

Biological resources (cells, tissues, bodily fluids or biomolecules) are considered essential raw material for the advancement of health-related biotechnology, for research and development in life sciences, and for ultimately improving human health. Stored in local biobanks, access to the human biological samples and related medical data for transnational research is often limited, in particular for the international life science industry. The recently established pan-European Biobanking and BioMolecular resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC) aims to improve accessibility and interoperability between academic and industrial parties to benefit personalized medicine, disease prevention to promote development of new diagnostics, devices and medicines. BBMRI-ERIC is developing the concept of Expert Centre as public-private partnerships in the precompetitive, not-for-profit field to provide a new structure to perform research projects that would face difficulties under currently established models of academic-industry collaboration. By definition, Expert Centres are key intermediaries between public and private sectors performing the analysis of biological samples under internationally standardized conditions. This paper presents the rationale behind the Expert Centres and illustrates the novel concept with model examples.

Chronotype and sleep duration: the influence of season of assessment.

Little is known about human entrainment under natural conditions, partly due to the complexity of human behavior, torn between biological and social time and influenced by zeitgebers (light-dark cycles) that are progressively "polluted" (and thereby weakened) by artificial light. In addition, data about seasonal variations in sleep parameters are scarce. We, therefore, investigated seasonal variation in cross-sectional assessments of sleep/wake times of 9765 subjects from four European populations (EGCUT = Estonian Genome Centre, University of Tartu in Estonia; KORA = Cooperative Health Research in the Region of Augsburg in Germany; KORCULA = The Korcula study in Croatia; and ORCADES = The Orkney Complex Disease Study in Scotland). We identified time-of-year dependencies for the distribution of chronotype (phase of entrainment assessed as the mid-sleep time point on free days adjusted for sleep deficit of workdays) in cohorts from Estonia (EGCUT) and Germany (KORA). Our results indicate that season (defined as daylight saving time - DST and standard zonetime periods - SZT) specifications of photoperiod influence the distribution of chronotype (adjusted for age and sex). Second, in the largest investigated sample, from Estonia (EGCUT; N = 5878), we could detect that seasonal variation in weekly average sleep duration was dependent on individual chronotype. Later chronotypes in this cohort showed significant variation in their average sleep duration across the year, especially during DST (1 h advance in social time from the end of March to end of October), while earlier chronotypes did not. Later chronotypes not only slept less during the DST period but the average chronotype of the population assessed during this period was earlier than during the SZT (local time for a respective time zone) period. More in detail, hierarchical multiple regression analyses showed that, beyond season of assessment (DST or SZT), social jetlag (SJl; the discrepancy between the mid sleep on free and work days - which varied with age and sex) contributed to a greater extent to the variation in sleep duration than chronotype (after taking into account factors that are known to influence sleep duration, i.e. age, sex and body mass index). Variation in chronotype was also dependent on age, sex, season of assessment and SJl (which is highly correlated with chronotype - SJl was larger among later chronotypes). In summary, subjective assessments of sleep/wake times are very reliable to assess internal time and sleep duration (e.g. reproducing sleep duration and timing tendencies related to age and sex across the investigated populations), but season of assessment should be regarded as a potential confounder. We identified in this study photoperiod (seasonal adaptation) and SJl as two main factors influencing seasonal variation in chronotype and sleep duration. In conclusion, season of assessment, sex and age have an effect on epidemiological variation in sleep duration, chronotype and SJl, and should be included in studies investigating associations between these phenotypes and health parameters, and on the development of optimal prevention strategies.

Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies.

OBJECTIVE: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. METHODS: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(-5) were considered significant. RESULTS: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(-5) , OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(-5) , OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. CONCLUSION: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated.

Feasibility of innovative dietary assessment in epidemiological studies using the approach of combining different assessment instruments.

OBJECTIVE: To assess the feasibility of combining short-term and long-term dietary assessment instruments as new concept for improving usual dietary intake assessment on the individual level. DESIGN: Feasibility study of completing three 24 h dietary recalls (24-HDR) and a self-administered food propensity questionnaire (FPQ). The 24-HDR was conducted by monthly telephone interviews, using EPIC-SOFT software. The FPQ was completely standardized across cohorts and offered either as a web-based tool or in paper format. SETTING: Random sample derived from five ongoing European cohort studies (EPIC-San Sebastian, EPIC-Florence, EPIC-Potsdam, Estonia Genome Center (EGC) and Norwegian Women and Cancer study (NOWAC)). SUBJECTS: A total of 400 participants. RESULTS: Overall, the total participation rate for the present study was 65.3 % (n 261). On average, completion of the 24-HDR was highest for the first 24-HDR (63.0 %) and decreased slightly for the second (60.3 %) and third 24-HDR (56.3 %). The proportions of selecting the web-based FPQ varied among the study centres, with the highest in EGC (92.9 %) and NOWAC (70.0 %) and the lowest in EPIC-San Sebastian (25.5 %) and EPIC-Potsdam (33.9 %). Web users rarely requested support and were younger and more highly educated than those who completed the paper format. CONCLUSIONS: The present study supports the feasibility of a combined application of three 24-HDR and an FPQ in culturally different populations. The varying acceptance of the web-based instrument across populations requires a flexible application of assessment instruments.

Quality, quantity and harmony: the DataSHaPER approach to integrating data across bioclinical studies.

BACKGROUND: Vast sample sizes are often essential in the quest to disentangle the complex interplay of the genetic, lifestyle, environmental and social factors that determine the aetiology and progression of chronic diseases. The pooling of information between studies is therefore of central importance to contemporary bioscience. However, there are many technical, ethico-legal and scientific challenges to be overcome if an effective, valid, pooled analysis is to be achieved. Perhaps most critically, any data that are to be analysed in this way must be adequately 'harmonized'. This implies that the collection and recording of information and data must be done in a manner that is sufficiently similar in the different studies to allow valid synthesis to take place. METHODS: This conceptual article describes the origins, purpose and scientific foundations of the DataSHaPER (DataSchema and Harmonization Platform for Epidemiological Research; http://www.datashaper.org), which has been created by a multidisciplinary consortium of experts that was pulled together and coordinated by three international organizations: P³G (Public Population Project in Genomics), PHOEBE (Promoting Harmonization of Epidemiological Biobanks in Europe) and CPT (Canadian Partnership for Tomorrow Project). RESULTS: The DataSHaPER provides a flexible, structured approach to the harmonization and pooling of information between studies. Its two primary components, the 'DataSchema' and 'Harmonization Platforms', together support the preparation of effective data-collection protocols and provide a central reference to facilitate harmonization. The DataSHaPER supports both 'prospective' and 'retrospective' harmonization. CONCLUSION: It is hoped that this article will encourage readers to investigate the project further: the more the research groups and studies are actively involved, the more effective the DataSHaPER programme will ultimately be.

Manifesto for a European anxiety disorders research network.

Despite the size, burden and costs of anxiety disorders, many patients remain unrecognised, and the effectiveness of evidence-based interventions in routine clinical practice can be disappointing. The European College of Neuropsychopharmacology (ECNP) has established the ECNP Network Initiative (ECNP-NI) to help meet the goal of extending current understanding of the causes of central nervous system disorders, thereby contributing to improvements in clinical outcomes and reducing the associated societal burden. The Anxiety Disorders Research Network (ADRN) has been adopted within the ECNP-NI: this consensus statement summarises its overall aims and objectives.

Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: a new approach for newborn screening follow-up.

OBJECTIVE: The advent of universal newborn hearing screening in the United States and other countries, together with the identification of genes involved in the process of hearing, have led to an increase in both the need and opportunity for accurate molecular diagnosis of patients with hearing loss. Deafness and hearing impairment have a genetic cause in at least half the cases. The molecular genetic basis for the majority of these patients remains obscure, however, because of the absence of associated clinical features in approximately 70% (ie, nonsyndromic hearing loss) of patients, genetic heterogeneity, and the lack of molecular genetic tests that can evaluate a large number of mutations across multiple genes. DESIGN: We report on the development of a diagnostic panel with 198 mutations underlying sensorineural (mostly nonsyndromic) hearing loss. This panel, developed on a microarray, is capable of simultaneous evaluation of multiple mutations in 8 genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5 and the mitochondrial genes encoding 12S rRNA and tRNA-Ser[UCN]). RESULTS: The arrayed primer extension array for sensorineural hearing loss is based on a versatile platform technology and is a robust, cost-effective, and easily modifiable assay. Because hearing loss is a major public health concern and common at all ages, this test is suitable for follow-up after newborn hearing screening and for the detection of a genetic etiology in older children and adults. CONCLUSIONS: Comprehensive and relatively inexpensive genetic testing for sensorineural hearing loss will improve medical management for affected individuals and genetic counseling for their families.