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Summary The International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here., The updated Guidelines for Stem Cell Research and Clinical Translation describe the ethical principles and best practices for basic, translational, and clinical research involving stem cells and human embryos. The updated Guidelines include new recommendations to address the recent scientific advances involving embryos, stem cell-based embryo models, chimeras, organoids, and genome editing.

Personalized medicine (PM) aims to harness a wave of ‘omics’ discoveries to facilitate research and discovery of targeted diagnostics and therapies and increase the efficiency of healthcare systems by predicting and treating individual predispositions to diseases or conditions. Despite significant investment, limited progress has been made bringing PM to market. We describe the major perceived regulatory, intellectual property, and reimbursement challenges to the development, translation, adoption, and implementation of PM products into clinical care. We conducted a scoping review to identify (i) primary challenges for the development and implementation of PM identified in the academic literature; (ii) solutions proposed in the academic literature to address these challenges; and (iii) gaps that exist in that literature. We identified regulatory barriers to PM development and recommendations in 344 academic papers. Regulatory uncertainty was a cross-cutting theme that appeared in conjunction with other themes including: reimbursement; clinical trial regulation; regulation of co-development; unclear evidentiary requirements; insufficient incentives for research and development; incompatible information systems; and different regulation of different diagnostics. To fully realize the benefits of PM for healthcare systems and patients, regulatory, intellectual property, and reimbursement challenges need to be addressed in lock step with scientific advances.

Global investments in cellular immunotherapies reflect their curative potential. Our landscape of clinical trials will aid developers, investors, adopters and payers in planning for adoption and implementation along realistic time horizons. Trend data enable stakeholders to adapt their business models and capacity to bring immunotherapies to the clinic. For cancer, trends suggest a shift from cancer vaccines to adoptive cellular transfer, alongside a focus on solid tumors. Academic centers, mainly in the USA, lead in early-phase clinical trials and target identification; but industry involvement has increased fourfold over the past two decades. Trends indicate an increasingly personalized approach to onco-immunology, which raises challenges for cost-effective manufacturing and delivery models. Overcoming these challenges provides opportunities for innovative biotechnology firms.

Summary We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials., Highlights • We assessed clinical trial publications of innovative cell-based interventions • Only 54.5% of completed trials reported results • Private clinics known to provide unproven stem cell therapies register “trials” • Trial reporting guidelines are needed, specific to early-phase clinical trials, Fung and colleagues assessed publication patterns of clinical trials of novel stem cell therapies. Trial results remain underreported and stem cell tourism clinics are promoting their clinic activities on trial registries. Clinical trial reporting guidelines specific to early-phase clinical trials are needed.

Editorial summary Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy.

Canada's Assisted Human Reproduction Act is long overdue for Parliamentary review. We argue that the current regulation of research using human reproductive materials is not proportionate, not responsive to the uncertain threats posed to human and environmental health and safety, and is not considerate of diverse values in a democratic society. We propose tailored regulatory carve-outs for in vitro research for currently prohibited activities, such as gene editing, and for the exercise of Ministerial Discretion for access by Canadians to experimental in vivo interventions that are currently prohibited, such as mitochondrial replacement therapy. Our recommendations are bounded by constitutional constraints that recognize political and practical challenges in keeping oversight of this research under Federal jurisdiction, whether conducted in academic or private sectors. The proposed nuanced regulatory scheme should be overseen by a new national Agency, modeled on a blend of the Canadian Stem Cell Oversight Committee and Assisted Human Reproduction Canada.

Background: To learn from the experiences of potential clinical trial participants, participants in a Phase 1 ocular gene therapy trial, and their partners to improve communications and tri...

We explore how principles predicting the success of a medical information commons (MIC) advantaged or disadvantaged three MIC initiatives in three Canadian provinces. Our MIC case examples demonstrate that practices and policies to promote access to and use of health information can help improve individual healthcare and inform a learning health system. MICs were constrained by heterogenous health information protection laws across jurisdictions and risk-averse institutional cultures. A networked approach to MICs would unlock even more potential for national and international data collaborations to improve health and healthcare.

Canadian academic and industry stakeholders are concerned about the inclusion of "virus-like particles or sub-viral particles" in the definition of New Substances Notification Regulations for Organisms (NSNR(O)) which impacts clinical cell and gene therapy and commercialization. The requirement of an independent 120 days Environment and Climate Change Canada (ECCC) review preceding a Health Canada review on quality and environmental concerns places an additional burden on Sponsors submitting clinical trial applications (CTA) and/or New Drug Submissions (NDS). A workshop initiated by CellCAN and BIOTECanada with participants from Environment and Climate Change Canada, Health Canada, the Public Health Agency of Canada and Innovation, Science and Economic Development (Ottawa, March 19, 2018) with invited stakeholders discussed approaches to streamline the environmental review process. The following main recommendations were the focus of the workshop: A regulatory policy to clarify Canadian Environmental Protection Act (CEPA)'s definition of "living organism." This is currently defined as "a substance that is an animate product of biotechnology." A regulatory policy could potentially exempt "human cells touched by biotechnology for use in human medicinal products" from this definition to clarify any unintended overreach of CEPA, particularly as it applies to non-genetically modified cell therapies.A guidance document to better interpret NSNR(O) Schedule 1 requirements by CTA/NDS sponsors to satisfy the environmental review process.An amendment at the level of regulations, to the NSNR (O) to create a deferment to postpone environmental assessment of micro-organisms used in the manufacturing during investigational clinical trials (pre-market stage). The regulations would apply at the time of market authorization evaluation and review, when sufficient clinical data on vector shedding has been collected, as part of the investigational clinical trials.Amendment to Schedule 4 of the CEPA to include the Food and Drugs Act and Regulations (Food and Drugs Act /FDR) as an exclusion to the application of CEPA. This would remove the current dual regulation of cell and gene therapies by both CEPA and Food and Drugs Act /FDR. These recommendations and other options were discussed at the workshop. These recommendations if adopted will significantly streamline the current regulatory burden and harmonize environmental assessment requirements with other jurisdictions.

Paul Hebert and colleagues first described DNA barcoding in 2003, which led to international efforts to promote and coordinate its use. Since its inception, DNA barcoding has generated considerable media coverage. We analysed whether this coverage reflected both the scientific and social mandates of international barcoding organizations. We searched newspaper databases to identify 900 English-language articles from 2003 to 2013. Coverage of the science of DNA barcoding was highly positive but lacked context for key topics. Coverage omissions pose challenges for public understanding of the science and applications of DNA barcoding; these included coverage of governance structures and issues related to the sharing of genetic resources across national borders. Our analysis provided insight into how barcoding communication efforts have translated into media coverage; more targeted communication efforts may focus media attention on previously omitted, but important topics. Our analysis is timely as the DNA barcoding community works to establish the International Society for the Barcode of Life.

Bio-repositories and databases for biomedical research enable the efficient community-wide sharing of reagents and data. These archives play an increasingly prominent role in the generation and dissemination of bioresources and data essential for fundamental and translational research. Evidence suggests, however, that current funding and governance models, generally short-term and nationally focused, do not adequately support the role of archives in long-term, transnational endeavours to make and share high-impact resources. Our qualitative case study of the International Knockout Mouse Consortium and the International Mouse Phenotyping Consortium examines new governance mechanisms for archive sustainability. Funders and archive managers highlight in interviews that archives need stable public funding and new revenue-generation models to be sustainable. Sustainability also requires archives, journal publishers, and funders to implement appropriate incentives, associated metrics, and enforcement mechanisms to ensure that researchers use archives to deposit reagents and data to make them publicly accessible for academia and industry alike.

Purpose: To discuss progress in research on choroideremia (CHM) and related retinopathies with special emphasis on gene therapy approaches.Methods: Biomedical and clinical researchers from across the world as well as representatives of the social science research community were convened to the 2nd International Scientific Symposium for Choroideremia in Denver, Colorado in June 2014 to enhance our understanding of CHM and accelerate the translation of research to clinical application for the benefit of those affected by CHM.Results: Pre-clinical research using cell and animal models continues to further our understanding in the pathogenesis of CHM as well as to demonstrate proof-of-concept for gene transfer strategies. With the advent of modern imaging technology, better outcome measures are being defined for upcoming clinical trials. Results from the first gene therapy trial in CHM show promise, with sustained visual improvement over 6 months post-treatment. Current and next-generation gene transf...

Background: The process of translating preclinical findings into a clinical setting takes decades. Previous studies have suggested that only 5-10% of the most promising preclinical studies are successfully translated into viable clinical applications. The underlying determinants of this low success rate (e.g. poor experimental design, suboptimal animal models, poor reporting) have not been examined in an empirical manner. Our study aims to determine the contemporary success rate of preclinical-to-clinical translation, and subsequently determine if an association between preclinical study design and translational success/failure exists. Methods: Established systematic review methodology will be used with regards to the literature search, article screening and study selection process. Preclinical, basic science studies published in high impact basic science journals between 1995 and 2015 will be included. Included studies will focus on publicly available interventions with potential clinical promise. The primary outcome will be successful clinical translation of promising therapies - defined as the conduct of at least one Phase II trial (or greater) with a positive finding. A case-control study will then be performed to evaluate the association between elements of preclinical study design and reporting and the likelihood of successful translation. Discussion: This study will provide a comprehensive analysis of the therapeutic translation from the laboratory bench to the bedside. Importantly, any association between factors of study design and the success of translation will be identified. These findings may inform future research teams attempting preclinical-to-clinical translation. Results will be disseminated to identified knowledge users that fund/support preclinical research.

Whereas biological materials were once transferred freely, there has been a marked shift in the formalisation of exchanges involving these materials, primarily through the use of Material Transfer Agreements (MTAs). This paper considers how risk aversion dominates MTA negotiations and the impact it may have on scientific progress. Risk aversion is often based on unwarranted fears of incurring liability through the use of a material or loss of control or missing out on commercialisation opportunities. Evidence to date has suggested that complexity tends to permeate even straightforward transactions despite extensive efforts to implement simple, standard MTAs. We argue that in most cases, MTAs need do little more than establish provenance, and any attempt to extend MTAs beyond this simple function constitutes stifling behaviour. Drawing on available examples of favourable practice, we point to a number of strategies that may usefully be employed to reduce risk-averse tendencies, including the promotion of simplicity, education of those engaged in the MTA process, and achieving a cultural shift in the way in which technology transfer office (TTO) success is measured in institutions employing MTAs.

International audience; High-throughput sequencing (HTS) of immunoglobulin (B-cell receptor, antibody) and T-cell receptor repertoires has increased dramatically since the technique was introduced in 2009 (1–3). This experimental approach explores the maturation of the adaptive immune system and its response to antigens, pathogens, and disease conditions in exquisite detail. It holds significant promise for diagnostic and therapy-guiding applications. New technology often spreads rapidly, sometimes more rapidly than the understanding of how to make the products of that technology reliable, reproducible, or usable by others. As complex technologies have developed, scientific communities have come together to adopt common standards, protocols, and policies for generating and sharing data sets, such as the MIAME protocols developed for microarray experiments. The Adaptive Immune Receptor Repertoire (AIRR) Community formed in 2015 to address similar issues for HTS data of immune repertoires. The purpose of this perspective is to provide an overview of the AIRR Community’s founding principles and present the progress that the AIRR Community has made in developing standards of practice and data sharing protocols. Finally, and most important, we invite all interested parties to join this effort to facilitate sharing and use of these powerful data sets (join@airr-community.org).

National and international public–private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership. This article describes eight core principles proposed by a diverse group of expert stakeholders to guide the formation of a successful, sustainable MIC. These principles promote formation of an ethically sound, inclusive, participant-centric MIC and provide a framework for advancing the policy response to data-sharing opportunities and challenges.

Les technologies de modification du génome promettent des avancées dans le traitement des maladies génétiques. Les auteurs abordent les enjeux éthiques et sociaux que soulèvent ces technologies, y compris leur utilisation dans des recherches précliniques, leur potentiel à résoudre les mutations somatiques et leur potentiel à modifier les lignées germinales qui peuvent être transmises aux prochaines générations. Ils demandent une réponse modérée de la part des leaders en santé, reposant sur une évaluation réaliste des avantages, des risques et des délais d’application clinique.

Genome editing technologies promise therapeutic advances for genetic diseases. We discuss the ethical and societal issues raised by these technologies, including their use in preclinical research, their potential to address mutations in somatic cells, and their potential to make germ line alterations that may be passed to subsequent generations. We call for a proportionate response from health leaders based on a realistic assessment of benefits, risks, and timelines for clinical translation.

Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterise novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-related toxicities; and (3) the need to develop efficient production/manufacturing processes to reduce costs. Here we discuss whether these challenges might better be addressed through forms of public-private research collaborations, including public-private partnerships, or whether these challenges are best addressed by way of standard market transactions. We analysed fourteen public-private relationships and 25 underlying agreements for the clinical development of cancer cellular immunotherapies in the United States. Most were based on bi-lateral research agreements and pure market transactions in the form of service contracts and technology licenses, which is representative of commercialization focus of the field. We make the strategic case that multi-party public-private partnerships may better advance cancer antigen discovery and characterization and improved cell processing/manufacturing and related activities. In the rush towards the competitive end of the translational continuum for cancer cellular immunotherapy and the attendant focus on commercialization, many gaps have appeared in our understanding of cellular biology, immunology, and bio-engineering. We conclude that the model of bi-lateral agreements between leading research institutions and the private sector may be inadequate to efficiently harness the interdisciplinary skills and knowledge of the public and private sectors to bring these promising therapies to the clinic for the benefit of cancer patients.

Life sciences research that uses genetic resources is increasingly collaborative and global, yet collective action remains a significant barrier to the creation and management of shared research resources. These resources include sequence data and associated metadata, and biological samples, and can be understood as a type of knowledge commons. Collective action by stakeholders to create and use knowledge commons for research has potential benefits for all involved, including minimizing costs and sharing risks, but there are gaps in our understanding of how institutional arrangements may promote such collective action in the context of global genetic resources. We address this research gap by examining the attributes of an exemplar global knowledge commons: The DNA barcode commons. DNA barcodes are short, standardized gene regions that can be used to inexpensively identify unknown specimens, and proponents have led international efforts to make DNA barcodes a standard species identification tool. Our research examined if and how attributes of the DNA barcode commons, including governance of DNA barcode resources and management of infrastructure, facilitate global participation in DNA barcoding efforts. Our data sources included key informant interviews, organizational documents, scientific outputs of the DNA barcoding community, and DNA barcode record submissions. Our research suggested that the goal of creating a globally inclusive DNA barcode commons is partially impeded by the assumption that scientific norms and expectations held by researchers in high income countries are universal. We found scientific norms are informed by a complex history of resource misappropriation and mistrust between stakeholders. DNA barcode organizations can mitigate the challenges caused by its global membership through creating more inclusive governance structures, developing norms for the community are specific to the context of DNA barcoding, and through increasing awareness and knowledge of pertinent legal frameworks.

As US President Barack Obama noted in his 2015 State of the Union address, precision medicine promises to deliver ‘the right treatments, at the right time, every time to the right person’ which ‘gives us one of the greatest opportunities for new medical breakthroughs that we have ever seen’.1 These comments were a prelude to a $215 million funding commitment by the President to his Precision Medicine Initiative, the aim of which is to ‘pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients’.2 The objectives include an undertaking to modernize the current regulatory landscape.