Organs-on-chip: The way forward.

Organ-on-chip (OoC) technology is thriving thanks to stem cells availability and international OoC programs. Concerted standardization, qualification, and independent testing of devices are needed to coherently develop OoC technology further and fulfill its potential in drug development, disease modeling, and personalized medicine. The OoC roadmap can lead the way forward.

Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development

The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Here, 46 leading experts from all stakeholders - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - worldwide have analyzed existing challenges and hurdles along the MPS-based assay life cycle in a second workshop of this kind in June 2019. They identified that the level of qualification of MPS-based assays for a given context of use and a communication gap between stakeholders are the major challenges for industrial adoption by end-users. Finally, a regulatory acceptance dilemma exists against that background. This t4 report elaborates on these findings in detail and summarizes solutions how to overcome the roadblocks. It provides recommendations and a roadmap towards regulatory accepted MPS-based models and assays for patients' benefit and further laboratory animal reduction in drug development. Finally, experts highlighted the potential of MPS-based human disease models to feedback into laboratory animal replacement in basic life science research.

Impact of organ-on-a-chip technology on pharmaceutical R&D costs.

Healthcare systems are faced with the challenge of providing innovative treatments, while shouldering high drug costs that pharmaceutical companies justify by the high costs of R&D. An emergent technology that could transform R&D efficiency is organ-on-a-chip. The technology bridges the gap between preclinical testing and human trials through better predictive models, significantly impacting R&D costs. Here, we present an expert survey on the future role of organ-on-a-chip in drug discovery and its potential quantitative impact. We find that the technology has the potential to reduce R&D costs significantly, driven by changes in direct costs, success rates and the length of the R&D process. Finally, we discuss regulatory challenges to efficiency improvements.

EUROCOURSE lessons learned from and for population-based cancer registries in Europe and their programme owners: Improving performance by research programming for public health and clinical evaluation.

UNLABELLED: Population-based cancer registries (CRs) in Europe have played a supportive, sometimes guiding, role in describing geographic variation of cancer epidemics and comparisons of oncological practice and preventive interventions since the 1950s for all types of cancer, separate and simultaneously. This paper deals with historical and longitudinal developments of the roughly 160 CRs and their programme owners (POs) that emerged since 1927 and accelerating since the late 70s especially in southern and continental Europe. About 40 million newly diagnosed patients were recorded since the 1950s out of a total of 100 million of whom almost 20 million are still alive and about 10% annually dying from cancer. The perception of unity in diversity and suboptimal comparability in performance and governance of CRs was confirmed in the EUROCOURSE (EUROpe against cancer: Optimisation of the Use of Registries for Scientific Excellence in research) European Research Area (ERA)-net coordination FP7 project of the European Commission (EU) which explored best practices, bottlenecks and future challenges of CRs. Regional oncologic and public health changes but also academic embedding of CRs varied considerably, although Anno 2012 optimal cancer surveillance indeed demanded intensive collaboration with professional and institutional stakeholders in two major areas (public health and clinical research) and five minor overlapping cancer research domains: aetiologic research, mass screening evaluation, quality of care, translational prognostics and survivorship. Each of these domains address specific study questions, mixes of disciplines, methodologies, additional data-sources and funding mechanisms. POs tended to become more and more public health institutes, Health ministries, but also comprehensive cancer centres and cancer societies through more and more funding at project or programme basis. POs were not easy to pin down because of their multiple, sometimes competitive (funding) obligations and increasing complexity of cancer surveillance. But they also rather seemed to need guiding principles for Governance of 'their' CR(s) as well as to appreciate value of collaborative research in Europe and shield CRs against unreasonable data protection in case of linkages. Despite access to specialised care related shortcomings, especially of survival cohort studies, European databases for studies of incidence and survival (such as ACCIS and EUREG on the one hand and EUROCARE and RARECARE on the other hand) have proved to be powerful means for comparative national or regional cancer surveillance. Pooling of comparable data will exhibit much instructive variation in time and place. If POs of CRs would consider multinational European studies of risk and prognosis of cancer more to serve their own regional or national interest, then progress in this field will accelerate and lead to more consistent funding from the EU. The current 20 million cancer survivors and their care providers are likely to appreciate more feedback. CONCLUSION: Most CRs remain uniquely able to report on progress against cancer by studies of variation in incidence (in time and place), detection and survival, referral and treatment patterns and their (side) effects in unselected patients, the latter especially in the (very) elderly. Programming and profiling its multiple and diverse clinical and prevention research is likely to promote involvement of public health and clinical stakeholders with a population-based research interest, increasingly patient groups and licensed 'buyers' of oncologic services.

EUROCOURSE recipe for cancer surveillance by visible population-based cancer RegisTrees in Europe: From roots to fruits.

Currently about 160 population-based cancer registries (CRs) in Europe have extensive experience in generating valid information on variation in cancer risk and survival with time and place. Most CRs cover all cancers, but some are confined to specific cancers or to children. They cover 15-55% of the populations in all of the larger member states of the European Union (EU), except the United Kingdom (UK), and 100% coverage in 80% of those with populations below 20 million. The EU FP 7 EUROCOURSE project, which operated in 2009-2013, explored the essential role of CRs in cancer research and public health, and also focused attention on their programme owners (POs) and stakeholders (e.g. cancer societies, oncological professionals, cancer patient groups, and planners, providers and evaluators of cancer care and mass screening). Generally, all CRs depended on their regional and/or national oncological context and were increasingly involved in population-based studies of quality of cancer care, long-term prognosis and quality of life, one third being very active. Within the public health domain, CRs, in addition to describing the variety of environmental and lifestyle-related cancer epidemics, have also contributed actively to aetiologic research by a European databases that showed wide discrepancies in cancer risk and survival across the EU, and in more depth by follow-up of cohorts and recruitment for case-control studies. CRs were also actively contributing to independent evaluation of mass screening as an intervention which affects quality of care and cancer mortality. The potential of CRs for clinical evaluation has grown substantially through interaction with clinical stakeholders and more incidentally biobanks, also with greater involvement of patient groups - with a special focus on elderly patients who generally do not take part in clinical trials. Whereas 25-35% of CRs are active in a range of cancer research areas, the rest have a low profile and usually provide only incidence and survival data. If they are unable to do so because POs and stakeholders do not demand it, they might also be inhibited by data protection restrictions, especially in German and French speaking countries. The value of population-based studies of quality of oncologic care and mass screening and the flawless reputation with regard to data protection of intensively used CRs in the northwest of Europe offered a sharp contrast, although they also follow the 1995 EU guideline on data protection. CRs thus offer a perfect example of what can be done with sensitive and minimal data, also when enriched by linkages to other databases. Intensive use of the data has allowed CR research departments to take on a visible expertise-based profile but a neutral in many public controversies in preventive oncology. Their management and fundability also appeared to benefit from externally classifying the wide array of tumour- or tract-specific intelligence and research activities for the various users in oncology and public health and also patients - who are the source of the data - are better informed. Transparency on what CRs enable may also improve through programmes of research have been deemed essential to our funding POs (ministries, cancer charities, cancer centres or public health institutes) who might benefit from some guidance to - often suboptimal -governance. Therefore, a metaphoric RegisTree has been developed for self-assessment and to clarify CR working methods and domain-specific performance to stakeholders and funding agencies, showing much room for development in many CRs. All in all, CRs are likely to remain unique sources of independent expert information on the burden of cancer, indispensable for cancer surveillance, with increased attention to cancer survivors, up to 4% of the population. Investments in the expanding CR network across Europe offer an excellent way forward for comparative future cancer surveillance with so many epidemiologic and clinical changes ahead.