Cellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter transcriptome profiles and complicate molecular diagnostics. To investigate this effect, we characterized such pre-analytical effects in 143 non-malignant liver samples obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts treated either with the Pringle manoeuvre or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-PCR. We found 179 mutually deregulated genes which point to elevated cytokine signaling with NFκB as a dominant pathway in ischemia responses. In contrast to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NFκB and MAPK pathways. FOS and JUN were down-regulated in steatosis compared to their up-regulation in normal livers. Surprisingly, molecular signatures of underlying primary and secondary cancers were present in non-tumor tissue. The reported inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a set of 230 pre-analytically highly robust genes identified from histologically normal livers (<2% covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications.

Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions-notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country-related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval-and the role of real-world evidence in the process-and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework-starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients.

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.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. This paper sets out the potential of biomarker testing, the unfolding precision and range of possible diagnosis and prediction, and the many obstacles to adoption. It offers case studies of biomarker testing in breast, ovarian, prostate, lung, thyroid and colon cancers, and derives specific lessons as to the potential and actual use of each of them. It also draws lessons about how to improve access and alignment, and to remedy the data deficiencies that impede development. And it suggests solutions to outstanding issues – notably including funding and the tangled web of obtaining reimbursement or equivalent coverage that Europe’s fragmented health system implies. It urges a European evolution towards an initial minimum testing scenario, which would guarantee universal access to a suite of biomarker tests for the currently most common conditions, and, further into the future, to an optimum testing scenario in which a much wider range of biomarker tests would be introduced and become part of a more sophisticated health system articulated around personalised medicine. For exploiting genomics to the full, it argues the need for a new policy framework for Europe. Biomarker testing is not an issue that can be treated in isolation, since the purpose of testing is to improve health. Its use is therefore always closely linked to specific health challenges and needs to be viewed in the broader policy context in the EU and more widely. The paper is the result of extensive engagement with experts and decision makers to develop the framework, and consequently represents a wide consensus of views on how healthcare systems should respond from push and pull factors at local, national and cross-border and EU level. It contains strong views and clear recommendations springing from the convictions of patients, clinicians, academics, medicines authorities, HTA bodies, payers, the diagnostic, pharmaceutical and ICT industries, and national policy makers.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions. One of the paradigmatic examples is BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, development is impeded by data deficiencies, and lack of policy alignment on standards, approval – and the role of real-world evidence in the process - and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework – starting with an update to outdated recommendations.

Comparison of published biomedical studies shows that a large proportion are irreproducible, causing severe damage to society and creating an image of wasted investments. These observations are of course damaging to the biomedical research field, which is currently full of future promise. Precision medicine and disease prevention are successful, but are progressing slowly due to irreproducible study results. Although standardization is mentioned as a possible solution, it is not always clear how this could decrease or prevent irreproducible results in biomedical studies. In this article more insight is given into what quality, norms, standardization, certification, accreditation and optimized infrastructure can accomplish to reveal causes of irreproducibility and increase reproducibility when collecting biomaterials. CEN and ISO standards for the sample pre-analytical phase are currently being developed with the support of the SPIDIA4P project, and their role in increasing reproducibility in both biomedical research and diagnostics is demonstrated. In particular, it is described how standardized methods and quality assurance documentation can be exploited as tools for: 1) recognition and rejection of 'not fit for purpose' samples on the basis of detailed sample metadata, and 2) identification of methods that contribute to irreproducibility which can be adapted or replaced.

Biopreservation and BiobankingVol. 17, No. 6 The Experts SpeakA Review of International Biobanks and Networks: Success Factors and Key Benchmarks—A 10-Year Retrospective ReviewEdited by Daniel Catchpoole, Authors: Lisa Devereux, Peter H. Watson, Anne-Marie Mes-Masson, Francisco Luna-Crespo, Gerry Thomas, Helen Pitman, Valerie Speirs, Andrew G. Hall, Nicole Bollinger, Manuel Posada, Hanns Lochmüller, Heather Thorne, Chon Boon Eng, Peter H.J. Riegman, Wayne Ng, and Alison Parry-JonesEdited by Daniel CatchpooleTumour Bank, Children's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Westmead, Australia.Search for more papers by this author, Authors: Lisa DevereuxLifepool and CASCADE-BROCADE, Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, Melbourne, Australia.Search for more papers by this author, Peter H. WatsonOffice of Biobank Education and Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.Biobanking and Biospecimen Research Services, Deeley Research Centre, BC Cancer Victoria Center, British Columbia, Canada.Search for more papers by this author, Anne-Marie Mes-MassonCentre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Institut du cancer de Montréal, Department of Medicine, Université de Montréal, Montreal, Canada.Search for more papers by this author, Francisco Luna-CrespoSpanish Cancer Research Centre—CNIO, Madrid, Spain.Search for more papers by this author, Gerry ThomasChernobyl Tissue Bank, London, United Kingdom.Search for more papers by this author, Helen PitmanNational Cancer Research Institute, London, United Kingdom.Search for more papers by this author, Valerie SpeirsUniversity of Aberdeen, United Kingdom.Search for more papers by this author, Andrew G. HallUniversity of Newcastle, Newcastle upon Tyne, United Kingdom.Search for more papers by this author, Nicole BollingerCHTN Central Coordinator, Cooperative Human Tissue Network (CHTN), Rockville, Maryland.Search for more papers by this author, Manuel PosadaDirector of the Institute of Rare Diseases Research, Director of the Spanish National Rare Diseases Biobank, Coordinator of EuroBioBank, President of the International Conference on Rare Diseases and Orphan Drugs (ICORD), Instituto de Salud Carlos III, Madrid, Spain.Search for more papers by this author, Hanns LochmüllerCHEO Institute, Ottawa, ON, Canada.Search for more papers by this author, Heather ThornekConFab National Manager, Research Department, Peter MacCallum Cancer Centre, Melbourne, Australia.Search for more papers by this author, Chon Boon EngThe National University of Singapore, Singapore, Singapore.Search for more papers by this author, Peter H.J. RiegmanHead Erasmus MC Tissue Bank, Erasmus MC Rotterdam, Rotterdam, The Netherlands.Search for more papers by this author, Wayne NgVictoria Cancer Biobank, Melbourne, Australia.Search for more papers by this author, and Alison Parry-JonesCardiff University School of Medicine, College of Biomedical and Life Sciences, Cardiff, United Kingdom.Search for more papers by this authorPublished Online:11 Dec 2019https://doi.org/10.1089/bio.2019.29060.djc.SIAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byEconomics of Biobanking: Business or Public Good? Literature Review, Structural and Thematic Analysis30 June 2022 | Social Sciences, Vol. 11, No. 7Finding the Value in Biobanks: Enhancing the CTRNet Locator Lise A. Matzke, Tamsin E. Tarling, Brent Gali, Simon Dee, Jodi LeBlanc, Suzanne Vercauteren, and Peter H. Watson19 April 2022 | Biopreservation and Biobanking, Vol. 20, No. 2Prospective Real-World Gynaecological Cancer Clinical Registry with Associated Biospecimens: A Collaborative Model to Promote Translational Research between GEICO and the Spanish Biobank Network13 April 2022 | Cancers, Vol. 14, No. 8The Importance of Cancer Biobanks in Low- and Middle-Income Countries16 March 2022Druggable genome and precision medicine in cancer: current challenges19 March 2021 | The FEBS Journal, Vol. 288, No. 21National Biobank Networking: The Case of Spain26 August 2021Moving with the Times: The Health Science Alliance (HSA) Biobank, Pathway to Sustainability27 March 2021 | Biomarker Insights, Vol. 16 Volume 17Issue 6Dec 2019 InformationCopyright 2019, Mary Ann Liebert, Inc., publishersTo cite this article:Edited by Daniel Catchpoole, Authors: Lisa Devereux, Peter H. Watson, Anne-Marie Mes-Masson, Francisco Luna-Crespo, Gerry Thomas, Helen Pitman, Valerie Speirs, Andrew G. Hall, Nicole Bollinger, Manuel Posada, Hanns Lochmüller, Heather Thorne, Chon Boon Eng, Peter H.J. Riegman, Wayne Ng, and Alison Parry-Jones.A Review of International Biobanks and Networks: Success Factors and Key Benchmarks—A 10-Year Retrospective Review.Biopreservation and Biobanking.Dec 2019.512-519.http://doi.org/10.1089/bio.2019.29060.djc.SIPublished in Volume: 17 Issue 6: December 11, 2019Online Ahead of Print:December 2, 2019PDF download

Optimal preservation and biobanking of renal tissue is vital for good diagnostics and subsequent research. Optimal cutting temperature (OCT) compound is a commonly used embedding medium for freezing tissue samples. However, due to interfering polymers in OCT, analysis as mass spectrometry (MS) is difficult. We investigated if the replacement of OCT with Cryo-Gel as embedding compound for renal biopsies would enable proteomics and not disturb other common techniques used in tissue diagnostics and research. For the present study, fresh renal samples were snap-frozen using Cryo-Gel, OCT and without embedding compound and evaluated using different techniques. In addition, tissue samples from normal spleen, skin, liver and colon were analyzed. Cryo-Gel embedded tissues showed good morphological preservation and no interference in immunohistochemical or immunofluorescent investigations. The quality of extracted RNA and DNA was good. The number of proteins identified using MS was similar between Cryo-Gel embedded samples, samples without embedding compound and OCT embedded samples. However, polymers in the OCT disturbed the signal in the MS, while this was not observed in the Cryo-Gel embedded samples. We conclude that embedding of renal biopsies in Cryo-Gel is an excellent and preferable alternative for OCT compound for both diagnostic and research purposes, especially in those cases where proteomic analysis might be necessary.

In May 2017, the European In Vitro Diagnostic Regulation (IVDR) entered into force and will apply to in vitro diagnostics from May 26th, 2022. This will have a major impact on the in vitro diagnostics (IVD) industry as all devices falling under the scope of the IVDR will require new or re-certification. It will also affect health institutions developing and using in-house devices. The IVDR also has implications with respect to product performance validation and verification including the pre-analytics of biological samples used by IVD developers and diagnostic service providers. In parallel to the IVDR, a series of standards on pre-analytical sample processing has been published by the International Organization for Standardization (ISO) and the European Committee for Standardization (CEN). These standards describe pre-analytical requirements for various types of analyses in various types of biospecimens. They are of relevance for IVD product developers in the context of (re)certification under the IVDR and to some extent also to devices manufactured and used only within health institutions. This review highlights the background and the rational for the pre-analytical standards. It describes the procedure that leads to these standards, the major implications of the standards and the requirements on pre-analytical workflows. In addition, it discusses the relationship between the standards and the IVDR.

Biobanks provide a critical infrastructure to support research in human health. Biospecimens and their accompanying data are increasingly needed to support biomedical research and clinical care. The original text was initially published in the Handbook for Cancer Research in Africa. The value of this publication is great as it underlines the importance of biobanks in Africa as a key resource to increase quality scientific research and participate in global health research. Therefore, a revision to extend these principles to other low resource contexts, to include updated material and references and add the topic of biobank sustainability were relevant.

The decision to use 10% neutral buffered formalin fixed, paraffin embedded (FFPE) archival pathology material may be dictated by the cancer research question or analytical technique, or may be governed by national ethical, legal and social implications (ELSI), biobank, and sample availability and access policy. Biobanked samples of common tumors are likely to be available, but not all samples will be annotated with treatment and outcomes data and this may limit their application. Tumors that are rare or very small exist mostly in FFPE pathology archives. Pathology departments worldwide contain millions of FFPE archival samples, but there are challenges to availability. Pathology departments lack resources for retrieving materials for research or for having pathologists select precise areas in paraffin blocks, a critical quality control step. When samples must be sourced from several pathology departments, different fixation and tissue processing approaches create variability in quality. Researchers must decide what sample quality and quality tolerance fit their specific purpose and whether sample enrichment is required. Recent publications report variable success with techniques modified to examine all common species of molecular targets in FFPE samples. Rigorous quality management may be particularly important in sample preparation for next generation sequencing and for optimizing the quality of extracted proteins for proteomics studies. Unpredictable failures, including unpublished ones, likely are related to pre-analytical factors, unstable molecular targets, biological and clinical sampling factors associated with specific tissue types or suboptimal quality management of pathology archives. Reproducible results depend on adherence to pre-analytical phase standards for molecular in vitro diagnostic analyses for DNA, RNA and in particular, extracted proteins. With continuing adaptations of techniques for application to FFPE, the potential to acquire much larger numbers of FFPE samples and the greater convenience of using FFPE in assays for precision medicine, the choice of material in the future will become increasingly biased toward FFPE samples from pathology archives. Recognition that FFPE samples may harbor greater variation in quality than frozen samples for several reasons, including variations in fixation and tissue processing, requires that FFPE results be validated provided a cohort of frozen tissue samples is available.

Healthcare innovation has never been more prevalent than it is today. But these innovations are only very slowly being embedded into Europe's healthcare systems. There is a huge capacity here in the EU to improve the health and quality of life of all citizens, but the extent to which it is happening is far from optimal. What is ringing out like a bell is that there is a clear need for better focus from policy makers, as this article explains. A policy bridge is required and a conscious decision among the powers-that-be in Europe needs to find a way to harmonise multiple strands of activity and responsibility in the health arena. The end goal will be for the EU to more effectively integrate the incredible advances in science into healthcare systems, for the benefit of all patients.

The growing interest in the molecular subclassification of colorectal cancers is increasingly facilitated by large multicenter biobanking initiatives. The quality of tissue sampling is pivotal for successful translational research. This study shows the quality of fresh frozen tissue sampling within a multicenter cohort study for colorectal cancer (CRC) patients. Each of the seven participating hospitals randomly contributed ten tissue samples, which were collected following Standard Operating Procedures (SOP) using established techniques. To indicate if the amount of intact RNA is sufficient for molecular discovery research and prove SOP compliance, the RNA integrity number (RIN) was determined. Samples with a RIN < 6 were measured a second time and when consistently low a third time. The highest RIN was used for further analysis. 91% of the tissue samples had a RIN ≥ 6 (91%). The remaining six samples had a RIN between 5 and 6 (4.5%) or lower than 5 (4.5%). The median overall RIN was 7.3 (range 2.9–9.0). The median RIN of samples in the university hospital homing the biobank was 7.7 and the median RIN for the teaching hospitals was 7.3, ranging from 6.5 to 7.8. No differences were found in the outcome of different hospitals ( p = 0.39). This study shows that the collection of high quality fresh frozen samples of colorectal cancers is feasible in a multicenter design with complete SOP adherence. Thus, using basic sampling techniques large patient cohorts can be organized for predictive and prognostic (bio)marker research for CRC.

The challenges faced in developing value-based diagnostics has resulted in few of these tests reaching the clinic, leaving many treatment modalities without matching diagnostics to select patients for particular therapies. Many patients receive therapies from which they are unlikely to benefit, resulting in worse outcomes and wasted health care resources. The paucity of value-based diagnostics is a result of the scientific challenges in developing predictive markers, specifically: (1) complex biology, (2) a limited research infrastructure supporting diagnostic development, and (3) the lack of incentives for diagnostic developers to invest the necessary resources. Better access to biospecimens can address some of these challenges. Methodologies developed to evaluate biomarkers from biospecimens archived from patients enrolled in randomized clinical trials offer the greatest opportunity to develop and validate high-value molecular diagnostics. An alternative opportunity is to access high-quality biospecimens collected from large public and private longitudinal observational cohorts such as the UK Biobank, the US Million Veteran Program, the UK 100,000 Genomes Project, or the French E3N cohort. Value-based diagnostics can be developed to work in a range of samples including blood, serum, plasma, urine, and tumour tissue, and better access to these high-quality biospecimens with clinical data can facilitate biomarker research.

In recent years, biobanks have emerged as vital research infrastructures with the aim of providing facilities, resources, and services to the scientific community in an open, transparent, and generous manner, enhancing excellence in biomedical research while guarding participants' rights and confidentiality. In this review, the authors present an overview of the general aspects of biobanking: from general operating procedures, ethical issues, and governance mechanisms to the importance of a robust information management system to track data. Moreover, the authors describe the importance of biobanks in epigenetic and epigenomic studies. In the context of human diseases, there is an increasing need to find new biomarkers to improve the accuracy of diagnosis, predict prognosis, and monitor the response to therapies. To overcome these needs, the scientific community must be provided with high-quality biological samples, along with associated data, in a manner that guarantees an individual's rights. In this framework, biobanks play a crucial role becoming the first step in the development of personalized medicine.

AimsCold ischaemic and formalin fixation time (CIT and FFT) are considered to be crucial parameters for intralaboratory variation in immunohistochemistry (IHC). Here we describe a new method to optimize IHC, by using control tissue blocks with known pre-analytical history and comparing the IHC outcome with digitized reference slides.Methods and resultsTissue specimens (two per tissue type) were divided into eight samples, which were subjected to different CIT and FFT. Immunohistochemistry was performed with 34 routinely used antibodies, following standard operating procedures. Relative staining intensity of four sections per slide was scored. Of the antibodies studied, seven were influenced by CIT, 13 by FFT and five by both parameters. IHC protocols were adapted until most sections on the slide showed the same intensity. Changing the antibody dilution for 10 protocols and the antigen retrieval method for six protocols improved the consistency of the IHC staining. Nine protocols could not be optimized. The optimized staining results were compared to reference slides and were found to be of adequate quality.ConclusionsIt was possible to optimize most IHC protocols by adapting the analytical, rather than the pre-analytical, phase. If global references can be established, this method could decrease interlaboratory variation, preceding standardization of the pre-analytical workflow.