Biomodifying the 'natural': from Adaptive Regulation to Adaptive Societal Governance.

Biomodifying technologies-such as gene editing, induced pluripotent stem cells, and bioprinting-are being developed for a wide range of applications, from pest control to lab-grown meat. In medicine, regulators have responded to the challenge of evaluating modified 'natural' material as a therapeutic 'product' by introducing more flexible assessment schemes. Attempts have also been made to engage stakeholders across the globe on the acceptable parameters for these technologies, particularly in the case of gene editing. Regulatory flexibility and stakeholder engagement are important, but a broader perspective is also needed to respond to the potential disruption of biomodification. Our case-study technologies problematize basic ideas-such as 'nature', 'product', and 'donation'-that underpin the legal categories used to regulate biotechnology. Where such foundational concepts are rendered uncertain, a socially responsive and sustainable solution would involve exploring evolutions in these concepts across different societies. We suggest that the global observatory model is a good starting point for this 'Adaptive Societal Governance' approach, in which a self-organizing network of scholars and interested parties could carry out the multi-modal (meta)analyses needed to understand societal constructions of ideas inherent to our understanding of 'life'.

Digital readiness in 3D bioprinting: software, governance and hospitals' proto-clinical interfaces.

Aim: To understand the process through which some hospitals have become ready to assimilate the digital technologies required for 3D bioprinting. By enhancing their digital readiness, hospitals will be able to develop the current proto-clinical potentialities of bioprinting. Materials & methods: We conducted interviews with bioprinting researchers, entrepreneurs and regulators in three countries (United Kingdom, Italy and Brazil). We analyzed bioprinting papers in which hospital-based researchers participated. We also analyzed the international bioprinting market. Results: Digital readiness is more advanced in some hospitals and countries, which have noticed the strategic relevance of bioprinting. Furthermore, it is strengthened by the reformulation of the relations between hospitals and other institutions, a phenomenon that is here interpreted with the concept of interfaces.

Promissory and protective imaginaries of regenerative medicine: Expectations work and scenario maintenance of disease research charities in the United Kingdom.

This article draws upon recent scholarship on technoscientific imaginaries and the sociology of technology expectations to reveal the mediating roles played by a number of disease-focused research charities in the United Kingdom. We examine the expectations they deal with about regenerative medicine research, and how they develop strategies to support and 'protect' potential medical scenarios for new therapies for dread diseases. In so doing, we develop and detail a concept of scenario maintenance to denote the strategic discursive and practical work of preserving stakeholders' faith in specific disease research pathways in the face of obstacles. Semi-structured in-depth interviews (N = 10) of research managers at nine research charities were qualitatively analysed, alongside a variety of charities' documentary data. Our analysis yielded three themes: managing and moderating media expectations; specifying expectations about disease-specific appropriateness of regenerative medicine; and maintaining scenarios of possible pathways for future success taking challenges into account.

Beyond the orthodox/CAM dichotomy: Exploring therapeutic decision making, reasoning and practice in the therapeutic landscapes of elite sports medicine.

Elite athletes face extreme challenges to perform at peak levels. Acute and chronic musculoskeletal injuries are an occupational hazard while pressures to return to play post-injury are commonplace. Therapeutic options available to elite athletes range from novel 'cutting edge' biomedical therapies, established biomedical and surgical techniques, and physiotherapy, to a variety of non-orthodox therapies. Little is known about how different treatment options are selected, evaluated, nor how their uses are negotiated in practice. We draw on data from interviews with 27 leading sports medicine physicians working in professional football and cycling in the UK, collected 2014-16. Using idea of the 'therapeutic landscape' as a conceptual frame, we discuss how non-orthodox tools, technologies and/or techniques enter the therapeutic landscape of elite sports medicine, and how the boundaries between orthodox and non-orthodox therapy are conceptualised and navigated by sports medicine practitioners. The data provide a detailed and nuanced examination of heterogenous therapeutic decision -making, reasoning and practice. Our data show that although the biomedical paradigm remains dominant, a wide range of non-orthodox therapies are frequently used, or authorised for use, by sports medicine practitioners, and this is achieved in complex and contested ways. Moreover, we situate debates around nonorthodox medicine practices in elite sports in ways that critically inform current theories on Complementary and Alternative Medicine (CAM)/biomedicine. We argue that existing theoretical concepts of medical pluralism, integration, diversity and hybridisation, which are used to explain CAMs through their relationships with biomedicine, do not adequately account for the multiplicity, complexity and contestation that characterise contemporary forms of CAM use in elite sport.

The emerging landscape of reimbursement of regenerative medicine products in the UK: publications, policies and politics.

AIM: This paper aims to map the trends and analyze key institutional dynamics that constitute the policies for reimbursement of regenerative medicine (RM), especially in the UK. MATERIALS & METHODS: Two quantitative publications studies using Google Scholar and a qualitative study based on a larger study of 43 semi-structured interviews. RESULTS: Reimbursement has been a growing topic of publications specific to RM and independent from orphan drugs. Risk-sharing schemes receive attention among others for dealing with RM reimbursement. Trade organizations have been especially involved on RM reimbursement issues and have proposed solutions. CONCLUSION: The policy and institutional landscape of reimbursement studies in RM is a highly variegated and conflictual one and in its infancy.

Where biomedicalisation and magic meet: Therapeutic innovations of elite sports injury in British professional football and cycling.

Injury is a conspicuous feature of the practice and public spectacle of contemporary elite sports. The paper argues that the 'biomedicalisation' thesis (medico-industrial nexus, techno-scientific drivers, medical optimisation, biologisation, the rise of evidence and health surveillance) goes some way to capturing the use in elite sports injury of some highly specialised mainstream therapies and some highly maverick biological therapies, which are described. Nevertheless, these main strands of biomedicalisation do not capture the full range of these phenomena in the contexts of sports medicine and athletes' practices in accessing innovative, controversial therapies. Drawing on multi-method qualitative research on top-level professional football and cycling in the UK, 2014-2016, we argue that concepts of 'magic' and faith-based healing, mediated by notions of networking behaviour and referral systems, furnish a fuller explanation. We touch on the concept of 'medical pluralism', concluding that this should be revised in order to take account of belief-based access to innovative bio-therapies amongst elite sportspeople and organisations.

Promissory identities: Sociotechnical representations & innovation in regenerative medicine.

The field of regenerative medicine (RM) is championed as a potential source of curative treatments and economic wealth, and initiatives have been launched in several countries to facilitate innovation within the field. As a way of examining the social dimensions of innovation within regenerative medicine, this paper explores the sociotechnical representations of RM technologies in the UK, and the tensions, affordances and complexities these representations present for actors within the field. Specifically, the paper uses the Science and Technology Studies-inspired notions of 'technology identity' and 'development space' to examine how particular technologies are framed and positioned by actors, and how these positionings subsequently shape innovation pathways. Four developing RM technologies are used as case studies: bioengineered tracheas; autologous chondrocyte implantation; T-cell therapies; and a 'point-of-care' cell preparation device. Using these case studies we argue that there are particular identity aspects that have powerful performative effects and provide momentum to innovation projects, and we argue that there are particular stakeholders in the UK RM landscape who appear to have considerable power in shaping these technology identities and thus innovation pathways.

Opening the gateways to market and adoption of regenerative medicine? The UK case in context.

Regenerative medicine is a site for opposing forces of gatekeeping and innovation. This applies both to regulation of market entry and to clinical adoption. Key gateways include the EU's Advanced Therapy Medicinal Products Regulation, technology assessment body NICE and commissioning/service contractor National Health Service England. The paper maps recent gatekeeping flexibilities, describing the range of gateways to market and healthcare adoption seen as alternatives to mainstream routes. The initiatives range from exemptions in pharmaceutical and ATMP regulations, through 'adaptive pathways' and 'risk-based' approaches, to special designation for promising innovation, value-based assessment and commissioner developments. Future developments are considered in the UK's 'accelerated access review'. Caution is urged in assessing the impact of these gateway flexibilities and their market and public health implications.

Comparing national home-keeping and the regulation of translational stem cell applications: An international perspective.

A very large grey area exists between translational stem cell research and applications that comply with the ideals of randomised control trials and good laboratory and clinical practice and what is often referred to as snake-oil trade. We identify a discrepancy between international research and ethics regulation and the ways in which regulatory instruments in the stem cell field are developed in practice. We examine this discrepancy using the notion of 'national home-keeping', referring to the way governments articulate international standards and regulation with conflicting demands on local players at home. Identifying particular dimensions of regulatory tools - authority, permissions, space and acceleration - as crucial to national home-keeping in Asia, Europe and the USA, we show how local regulation works to enable development of the field, notwithstanding international (i.e. principally 'western') regulation. Triangulating regulation with empirical data and archival research between 2012 and 2015 has helped us to shed light on how countries and organisations adapt and resist internationally dominant regulation through the manipulation of regulatory tools (contingent upon country size, the state's ability to accumulate resources, healthcare demands, established traditions of scientific governance, and economic and scientific ambitions).

Are there specific translational challenges in regenerative medicine? Lessons from other fields.

There is concern that translation 'from bench to bedside' within regenerative medicine (RM) will fail to materialize, or will be dismally slow, due to various challenges arising from the highly novel and disruptive nature of RM. In this article, we provide a summary of these challenges, and we critically engage with the notion that such challenges are specific to RM. It is important, we argue, not to overstate the exceptional nature of RM, as valuable lessons can be learned from elsewhere in medicine. Using several examples of technology adoption, we suggest that emerging RM products and procedures will have to work hard to find or create an adoption space if translation into the clinic is to be successful.

Law's performativities: shaping the emergence of regenerative medicine through European Union legislation.

The paper undertakes a textual and documentary analysis of the Advanced Therapy Medicinal Products Regulation, which was passed into law in the European Union (EU) in 2007. This law is significant for the development of regenerative medicine in the EU and globally. Regulatory texts such as this one provide significant material for addressing key concerns in recent theorising about innovative technologies in socio-legal studies, innovation studies, and science and technology studies. These concerns include expectations about future technologies and economic sector-building. By revisiting philosopher J.L. Austin's well-known work on How to Do Things with Words, this paper deploys his concepts of performative utterances to inform its analysis. Pursuing Austin's and later commentators' analysis of performatives in language use, and drawing on Lindsay Prior's application of actor-network theory to documents, the analysis shows two different types of performativity at work in and through the document. These are termed 'generative' and 'enactive' performativity. The 'enactive' type includes 'legislative' and 'social' forms. In addition, a more conventional content analysis reveals a range of actions, both legislative and discursive, in the regulatory document. The analysis shows a tension between standardisation and imprecision in the conceptual detailing of the document. Legislative texts produced through established politico-legal conventions are a special class of document that should be accorded a more prominent place in understanding the role of political governance processes in shaping emergent technoscientific fields and sectors.

Governing biological material at the intersection of care and research: the use of dried blood spots for biobanking.

A series of governance issues currently surrounds the multiple uses and multiple users of dried blood spots (DBS) for research purposes. Internationally there is a discussion on storing DBS resulting from newborn screening for public health and using them as the basis for large biobank-like collections to facilitate biomedical research. If such a transformation were to be formalized, then DBS would sit at the intersection of care (ie, public health) and research, with the mechanisms through which such a collection could be managed not totally self-evident. What is more, a DBS collection raises questions about the fuzzy boundaries between privacy and anonymity; how to control or define quality control uses of DBS; medical vs nonmedical uses; as well as benefit sharing and stakeholder involvement. Our goal here is to explore some of the key questions relating to DBS governance by way of the bio-objects and bio-objectification concepts. By embracing - rather than resisting to - the blurring of boundaries and problems in categorization that have come to characterize bio-objects and bio-objectification processes recently described in this journal, we attempt to highlight some issues that might not be currently considered, and to point to some possible directions to go (or avoid). Building from our knowledge of the current DBS situation in the Netherlands, we outline questions concerning the uses, management, collection, and storage of DBS.

The legal landscape for advanced therapies: material and institutional implementation of European Union rules in France and the United Kingdom.

In 2007, the European Union adopted a lex specialis, Regulation (EC) No. 1394/2007 on advanced therapy medicinal products (ATMPs), a new legal category of medical product in regenerative medicine. The regulation applies to ATMPs prepared industrially or manufactured by a method involving an industrial process. It also provides a hospital exemption, which means that medicinal products not regulated by EU law do not benefit from a harmonized regime across the European Union but have to respect national laws. This article describes the recent EU laws, and contrasts two national regimes, asking how France and the United Kingdom regulate ATMPs which do and do not fall under the scope of Regulation (EC) No. 1394/2007. What are the different legal categories and their enforceable regimes, and how does the evolution of these highly complex regimes interact with the material world of regenerative medicine and the regulatory bodies and socioeconomic actors participating in it?

Resisting the screening imperative: patienthood, populations and politics in prostate cancer detection technologies for the UK.

The introduction of mass screening programmes in the UK has been controversial. It is instructive to examine medical conditions for which screening has been actively considered but not introduced, such as prostate cancer. Incidence of the disease has escalated during the last 20 years, partly due to the upsurge in use of PSA (prostate-specific antigen) detection technology. The controversy is moving into a new phase, associated with the development of new molecular genetic biomarkers and tests derived from genome-association studies. The paper outlines the most recent scientific and technological developments for the three types of detection technology - PSA, genetic, and genomic. Applying concepts of risk, technology governance and technology expectations, it is shown that central public health governance actors continue to resist the tidal wave of new technologies through a variety of increasingly diverse governance modes. In the case of PSA, a governance trend moving beyond 'responsibilisation' to citizen rights is shown, whereas in the case of genetic tests and genomic risk profiling, state public health agencies are shown to be engaging in a form of technology expectation management, as it responds to a new marketplace of private commercial testing and mediatised science-based visions of future healthcare.

State strategies of governance in biomedical innovation: aligning conceptual approaches for understanding 'Rising Powers' in the global context.

BACKGROUND: 'Innovation' has become a policy focus in its own right in many states as they compete to position themselves in the emerging knowledge economies. Innovation in biomedicine is a global enterprise in which 'Rising Power' states figure prominently, and which undoubtedly will re-shape health systems and health economies globally. Scientific and technological innovation processes and policies raise difficult issues in the domains of science/technology, civil society, and the economic and healthcare marketplace. The production of knowledge in these fields is complex, uncertain, inter-disciplinary and inter-institutional, and subject to a continuing political struggle for advantage. As part of this struggle, a wide variety of issues - regulation, intellectual property, ethics, scientific boundaries, healthcare market formation - are raised and policy agendas negotiated. METHODS: A range of social science disciplines and approaches have conceptualised such innovation processes. Against a background of concepts such as the competition state and the developmental state, and national innovation systems, we give an overview of a range of approaches that have potential for advancing understanding of governance of global life science and biomedical innovation, with special reference to the 'Rising Powers', in order to examine convergences and divergences between them. Conceptual approaches that we focus on include those drawn from political science/political economy, sociology of technology; Innovation Studies and Science & Technology Studies. The paper is part of a project supported by the UK ESRC's Rising Powers programme. RESULTS: We show convergences and complementarities between the approaches discussed, and argue that the role of the national state itself has become relatively neglected in much of the relevant theorising. CONCLUSIONS: We conclude that an approach is required that enables innovation and governance to be seen as 'co-producing' each other in a multi-level, global ecology of innovation, taking account of the particular, differing characteristics of different emerging scientific fields and technologies. We suggest key points to take account of in order in the future to move toward a satisfactory integrative conceptual framework, capable of better understanding the processes of the emergence, state steerage and transnational governance of innovative biomedical sectors in the Rising Powers and global context.

Purity and the dangers of regenerative medicine: regulatory innovation of human tissue-engineered technology.

This paper examines the development of innovation in human tissue technologies as a form of regenerative medicine, firstly by applying 'pollution ideas' to contemporary trends in its risk regulation and to the processes of regulatory policy formation, and secondly by analysing the classificatory processes deployed in regulatory policy. The analysis draws upon data from fieldwork and documentary materials with a focus on the UK and EU (2002-05) and explores four arenas: governance and regulatory policy; commercialisation and the market; 'evidentiality' manifest in evidence-based policy; and publics' and technology users' values and ethics. The analysis suggests that there is a trend toward 'purification' across these arenas, both material and socio-political. A common process of partitioning is found in stakeholders' attempts to define a clear terrain, which the field of tissue-engineered technology might occupy. We conclude that pollution ideas and partitioning processes are useful in understanding regulatory ordering and innovation in the emerging technological zone of human tissue engineering.

Regulating Hybrids: 'Making a Mess' and 'Cleaning Up' in Tissue Engineering and Transpecies Transplantation.

This paper explores the institutional regulation of novel biosciences, hybrid technologies that often disturb and challenge existing regulatory frameworks. Developing a conceptual vocabulary for understanding the relationship between material and institutional hybrids, the paper compares human tissue engineering (TE) and xenotransplantation (XT), areas of innovation which regulators have sought to govern separately and in isolation from one another. Contrasting definitional boundaries and regulatory mechanisms partition them socio-institutionally. But despite these attempts at purification, TE and XT have proven increasingly difficult to tell apart in practical and material terms. Human and animal matters, cell cultures and tissue products have much greater corporeal connection than has been institutionally recognized, and are therefore a source of acute instability in the regulation of implants and transplants. This paper tells the story of how the messy worlds of TE and XT have leaked into one another, calling into question the abilities of regulation to adequately control hybrid innovations.

A systematic review of the effect of primary care-based service innovations on quality and patterns of referral to specialist secondary care.

BACKGROUND: Innovations are proliferating at the primary-secondary care interface, affecting referral to secondary care and resource use. Evidence about the range of effects and implications for the healthcare system of different types of innovation have not previously been summarised. AIM: To review the available evidence on initiatives affecting primary care referral to specialist secondary care. SETTING: Studies of primary-secondary care interface. METHOD: Systematic review of trials, using adapted Cochrane Collaboration (effective practice and organisation of care) criteria. Studies from 1980 to 2001 were identified from a wide range of sources. Strict inclusion criteria were applied, and relevant clinical, service and cost data extracted using an agreed protocol. The main outcome measures were referral rates to specialist secondary care. RESULTS: Of the 139 studies initially identified. 34 met the review criteria. An updated search added a further 10 studies. Two studies provided economic analysis only. Referral was not the primary outcome of interest in the majority of included studies. Professional interventions generally had an impact on referral rates consistent with the intended change in clinician behaviour. Similarly, specialist 'outreach' or other primary care-based specialist provider schemes had at least a small effect upon referral rates to secondary care with the direction of effect being that intended or rational from a clinical and sociological perspective. Of the financial interventions, one was aimed primarily at changing the numbers or proportion of referrals from primary to specialist secondary care, and the direction of change was as expected in all cases. The quality of the reporting of the economic components of the 14 studies giving economic data was poor in many cases. When grouped by intervention type, no overall pattern of change in referral costs or total costs emerged. CONCLUSION: The studies identified were extremely diverse in methodology, clinical subject, organisational form, and quality of evidence. The number of good quality evaluations of innovative schemes to enhance the existing capacity of primary care was small, but increasing. Well-evaluated service initiatives in this area should be supported. Organisational innovations in the structure of service provision need not increase total costs to the National Health Service (NHS), even though costs associated with referral may increase. This review provides limited, partial, and conditional support for current primary care-oriented NHS policy developments in the United Kingdom.