Industry, experts and the role of the 'invisible college' in the dissemination of non-invasive prenatal testing in the US.

Enthusiasm for so-called 'personalized' or 'precision' medicine has encouraged the growth of the molecular diagnostics industry and the proliferation of high-priced proprietary tests that can predict, diagnose or inform the treatment of diverse clinical conditions. Through a case study of non-invasive prenatal testing (NIPT), we explore how the mechanisms governing the development and dissemination of this novel prenatal screening test are most aptly understood as a 'regulatory regime.' We describe how private actors tied to the manufacturers of this test form a network of "experts" that contribute to the coordination of this regime by virtue of their efforts to navigate the governance of test adoption and also form spaces in which the standards governing test adoption are developed. We draw attention to private actors in this regime to demonstrate that they are a constitutive element of the public policy system governing biomedical innovation and adoption. Through this case study of NIPT we deepen our previous analysis of the role of consultants in navigating and shaping a regulatory regime (Holloway and Miller, 2020) and offer new insight about how scientists work with consultants to shape a regulatory regime that serves industry interests. Our work indicates that the private actors tied to the manufacturers of NIPT (experts employed by industry to court scientists and lobby payers, scientists collaborating with industry, key opinion leaders involved with clinical practice guidelines, lobbyists and consultants), constitute an 'invisible college' that navigates the governance of test adoption. The formations and negotiations over standards for NIPT identified in this paper comprise a new institutional norm: a polycentric regulatory regime permeated by commercial interests. The institutionalization of this regime has implications for accountability, transparency and test quality amidst a proliferation of new proprietary molecular tests.'

Introducing responsible innovation in health: a policy-oriented framework.

The scholarship on responsible research and innovation (RRI) aims to align the processes and outcomes of innovation with societal values by involving a broad range of stakeholders from a very early stage. Though this scholarship offers a new lens to consider the challenges new health technologies raise for health systems around the world, there is a need to define the dimensions that specifically characterise responsible innovation in health (RIH). The present article aims to introduce an integrative RIH framework drawing on the RRI literature, the international literature on health systems as well as specific bodies of knowledge that shed light on key dimensions of health innovations. Combining inductive and deductive theory-building strategies and concomitant with the development of a formal tool to assess the responsibility of innovations, we developed a framework that is comprised of nine dimensions organised within five value domains, namely population health, health system, economic, organisational and environmental. RIH provides health and innovation policy-makers with a common framework that supports the development of innovations that can tackle significant system-level challenges, including sustainability and equity.

Public involvement and health research system governance: a qualitative study.

BACKGROUND: Interest in public involvement in health research projects has led to increased attention on the coordination of public involvement through research organisations, networks and whole systems. We draw on previous work using the 'health research system' framework to explore organisational actors and stewardship functions relevant to governance for public involvement. METHODS: To inform efforts in Ontario, Canada, to mobilise public involvement across the provincial health research enterprise, we conducted an exploratory, qualitative descriptive study of efforts in two jurisdictions (England, United Kingdom, and Alberta, Canada) where there were active policy efforts to support public involvement, alongside jurisdiction-wide efforts to mobilise health research. Focusing on the efforts of public sector organisations with responsibility for funding health research, enabling public involvement, and using research results, we conducted in-depth, semi-structured interviews with 26 expert informants and used a qualitative thematic approach to explore how the involvement of publics in health research has been embedded and supported. RESULTS: We identified three sets of common issues in efforts to advance public involvement. First, the initial aim to embed public involvement leveraged efforts to build self-conscious research 'systems', and mobilised policy guidance, direction, investment and infrastructure. Second, efforts to sustain public involvement aimed to deepen involvement activity and tackle diversity limitations, while managing the challenges of influencing research priorities and forging common purpose on the evaluation of public involvement. Finally, public involvement was itself an influential force, with the potential to reinforce - or complicate - the ties that link actors within research systems, and to support - or constrain - the research system's capacity to serve and strengthen health systems. CONCLUSIONS: Despite differences in the two jurisdictions analysed and in the organisation of public involvement within them, the supporters and stewards of public involvement sought to leverage research systems to advance public involvement, anticipated similar opportunities for improvement in involvement processes and identified similar challenges for future involvement activities. This suggests the value of a health research system framework in governance for public involvement, and the importance of public involvement for the success of health research systems and the health systems they aim to serve.

Public involvement in health research systems: a governance framework.

BACKGROUND: Growing interest in public involvement in health research has led to organisational and policy change. Additionally, an emerging body of policy-oriented scholarship has begun to identify the organisational and network arrangements that shape public involvement activity. Such developments suggest the need to clearly conceptualise and characterise public involvement in health research in terms of governance. METHODS: We drew on an established health research system framework to analyse governance functions related to public involvement, adapting scoping review methods to identify evidence from a corpus of journal papers and policy reports. We drew on the logics of aggregation and top down configuration, using a qualitative interpretive approach to combine and link findings from different studies into framework categories. RESULTS: We identified a total of 32 scholarly papers and 13 policy reports (n = 45 included papers) with relevance to governance for public involvement. Included papers were broadly consonant in identifying the need for activity to specify and support public involvement across all four governance functions of stewardship, financing, creating and sustaining resources, and research production and use. However, different visions for public involvement, and the activity required to implement it and achieve impact, were particularly evident with respect to the stewardship function, which seeks to set overall directions for research while addressing the potentially competing demands of a system's many constituents. CONCLUSIONS: A governance perspective has considerable value for public involvement in health research systems, supporting efforts to coordinate and institutionalise the burgeoning public involvement enterprise. Furthermore, it highlights challenges for what is, ultimately, a highly political intervention, suggesting that diverse publics must be both involved within health research systems and enrolled as governors of them.

Controversy and debate on clinical genomics sequencing-paper 1: genomics is not exceptional: rigorous evaluations are necessary for clinical applications of genomic sequencing.

Next generation genomic sequencing (NGS) technologies-whole genome and whole exome sequencing-are now cheap enough to be within the grasp of many health care organizations. To many, NGS is symbolic of cutting edge health care, offering the promise of "precision" and "personalized" medicine. Historically, research and clinical application has been a two-way street in clinical genetics: research often driven directly by the desire to understand and try to solve immediate clinical problems affecting real, identifiable patients and families, accompanied by a low threshold of willingness to apply research-driven interventions without resort to formal empirical evaluations. However, NGS technologies are not simple substitutes for older technologies and need careful evaluation for use as screening, diagnostic, or prognostic tools. We have concerns across three areas. First, at the moment, analytic validity is unknown because technical platforms are not yet stable, laboratory quality assurance programs are in their infancy, and data interpretation capabilities are badly underdeveloped. Second, clinical validity of genomic findings for patient populations without pre-existing high genetic risk is doubtful, as most clinical experience with NGS technologies relates to patients with a high prior likelihood of a genetic etiology. Finally, we are concerned that proponents argue not only for clinically driven approaches to assessing a patient's genome, but also for seeking out variants associated with unrelated conditions or susceptibilities-so-called "secondary targets"-this is screening on a genomic scale. We argue that clinical uses of genomic sequencing should remain limited to specialist and research settings, that screening for secondary findings in clinical testing should be limited to the maximum extent possible, and that the benefits, harms, and economic implications of their routine use be systematically evaluated. All stakeholders have a responsibility to ensure that patients receive effective, safe health care, in an economically sustainable health care system. There should be no exception for genome-based interventions.

Governing population screening in an age of expansion: The case of newborn screening.

Newborn bloodspot screening is one of the most enduring and successful population screening initiatives. Yet technological innovation to permit simultaneous measurement of multiple biomarkers - and potentially, entire genomes - has spurred expansion and debate. Through a cross-jurisdictional comparison, we describe the varied roles and reach of screening-related governance structures in the United States, the United Kingdom, New Zealand and Canada, and highlight the distinct values and resources brought to bear by the genetics, public health and maternal-child health communities in adjudicating the benefits and burdens of expanded newborn screening. We call for the expansion of formal governance structures that are balanced in resources and perspective and mandated to ensure that the organization and delivery of newborn screening achieves optimal quality.

How do values shape technology design? An exploration of what makes the pursuit of health and wealth legitimate in academic spin-offs.

By actively supporting cooperation between academia, clinical settings and industry, several policy initiatives assume that the two policy agendas of health and wealth can be reconciled through the development of health technology. Our goal in this article is to shed light on the way the concurrent pursuit of health and wealth operates in practice by examining the valuation schemes, actions and decisions that shaped technology development in three Canadian spin-offs. Drawing on the sociology of judgement, our analytical framework conceives of technology development as a purposive collective action that unfolds in a normatively heterogeneous context (one pervaded with both corporate and public service mission values and norms). Our qualitative empirical analyses explore four valuation schemes and their corresponding regimes of engagement that characterise why and how technology developers commit themselves to addressing certain clinical, interactional, organisational and economic concerns throughout the development process. Our discussion suggests that the ability to reconcile health and wealth goals is to be found in the moral repertoires that provide meaning to, and render coherent technology developers' participation in corporate activities driven by economic growth.

Leveraging the "living laboratory": on the emergence of the entrepreneurial hospital.

For years, scholars have debated the "commercial ethos" in higher education, and the rise of the entrepreneurial university. But what of the "entrepreneurial hospital"? Largely unnoticed by scholars, this unique organisational form differs from the entrepreneurial university in some significant ways, not least in its capacity to use its innovations, and to count patients-and even patient populations-amongst its human capital. Accordingly, this article provides an initial conceptualisation of the entrepreneurial hospital, along with an exploration of its larger implications. Using twenty-six semi-structured interviews with key-informants (2008-2009), who work in two networked organisations within a single academic health science system in a Canadian province, our analysis identifies distinctive characteristics of an entrepreneurial hospital. Informed by grounded theory, especially situational analysis, we derive from our data an illustration of potentially incommensurate understandings of the entrepreneurial hospital's resources. On one hand, our study participants view patients and patient populations as a resource for research, linking its value to the contribution it can make to improved, more cost-effective care. On the other hand, some also see commercial potential in this resource. In both cases, exploitation is accompanied by perceived obligations to make proper use of patient populations, and to "give back" to the public-at-large, including through the entrepreneurial search for new ways of mobilising the resources of publicly-funded health care. Thus, a key task of the entrepreneurial hospital is to invent and mediate new uses for its care infrastructure and the unique resource constituted by patient populations. By drawing together care and research in new ways, the entrepreneurial hospital promises increased capacity for biomedical innovation. Yet, as it invents and mediates new uses for patient populations and health care infrastructure, the entrepreneurial hospital stands to significantly redefine both systems of care and the bonds of social solidarity.

One thing leads to another: the cascade of obligations when researchers report genetic research results to study participants.

Even as debate continues about the putative obligation to proactively report genetic research results to study participants, there is an increasing need to attend to the obligations that might cascade from any initial report. We conducted an international, quasi-experimental survey of researchers involved in autism spectrum disorders (ASD) and cystic fibrosis (CF) genetics to explore perceived obligations to ensure updated information or relevant clinical care subsequent to any initial communication of research results, and factors influencing these attitudes. 5-point Likert scales of dis/agreement were analyzed using descriptive and multivariate statistics. Of the 343 respondents (44% response rate), large majorities agreed that in general and in a variety of hypothetical research contexts, research teams that report results should ensure that participants gain subsequent access to updated information (74-83%) and implicated clinical services (79-87%). At the same time, researchers perceived barriers restricting access to relevant clinical care, though this was significantly more pronounced (P<0.001) for ASD (64%) than CF (34%). In the multivariate model, endorsement of cascading obligations was positively associated with researcher characteristics (eg, clinical role/training) and attitudes (eg, perceived initial reporting obligation), and negatively associated with the initial report of less scientifically robust hypothetical results, but unaffected by perceived or hypothetical barriers to care. These results suggest that researchers strongly endorse information and care-based obligations that cascade from the initial report of research results to study participants. In addition, they raise challenging questions about how any cascading obligations are to be met, especially where access challenges are already prevalent.

What does 'respect for persons' require? Attitudes and reported practices of genetics researchers in informing research participants about research.

BACKGROUND: It has been suggested that researchers are obliged to offer summary findings to research participants to demonstrate respect for persons, and that this may increase public trust in, and awareness of, the research enterprise. Yet little research explores researchers' attitudes and practices regarding the range of initiatives that might serve these ends. METHODS: Results of an international survey of 785 eligible authors of genetics research studies in autism or cystic fibrosis are reported. RESULTS: Of 343 researchers who completed the survey (44% response rate), the majority agreed that their team should (i) inform participants of summary findings (90.7%) and (ii) ensure they gain an awareness of developments in the field (86.9%). Additionally, the majority reported that in practice, their team (i) informs participants of summary findings (69.4%) and (ii) provides other types of relevant non-results information (eg, state of science in the field, opportunities for research participation) (67.9%). CONCLUSION: Researchers endorsed the obligation of communicating with research participants by providing summary findings and other research-related information in equal measure. In light of these findings, it is suggested that while the provision of summary results may contribute to efforts to discharge the obligation of respect for persons, it may be neither a necessary nor a sufficient means to this end.

Not so simple: a quasi-experimental study of how researchers adjudicate genetic research results.

Ethicists contend that researchers are obliged to report genetic research findings to individual study participants when they are clinically significant, that is, when they are clinically useful or personally meaningful to participants. Yet whether such standards are well understood and can be consistently applied remains unknown. We conducted an international, cross-sectional survey of cystic fibrosis (CF) and autism genetics researchers using a quasi-experimental design to explore factors influencing researchers' judgments. Eighty percent of researchers agreed, in principle, that clinically significant findings should be reported to individual participants. Yet judgments about when a specific finding was considered clinically significant or warranted reporting varied by scientific factors (replication, robustness, intentionality, and disease context), capacity of the research team to explain the results, and type of research ethics guidance. Further, judgments were influenced by the researchers' disease community (autism or CF), their primary role (clinical, molecular, statistical) and their beliefs regarding a general reporting obligation. In sum, judgments about the clinical significance of genetic research results, and about whether they should be reported, are influenced by scientific parameters as well as contextual factors related to the specific research project and the individual researcher. These findings call into question the assumption that the conditions under which an obligation to disclose arises are uniformly understood and actionable. Adjudicating the clinical readiness of provisional data may be a responsibility better suited to evaluative experts at arms' length of the provisional data in question, rather than a responsibility imposed upon researchers themselves.

What is a meaningful result? Disclosing the results of genomic research in autism to research participants.

Developments in genomics research have been accompanied by a controversial ethical injunction: that researchers disclose individually relevant research results to research participants. With the explosion of genomic research on complex psychiatric conditions such as autism, researchers must increasingly contend with whether--and which results--to report. We conducted a qualitative study with researchers and participants involved in autism genomics research, including 4 focus groups and 23 interviews with parents of autistic children, and 23 interviews with researchers. Respondents considered genomic research results 'reportable' when results were perceived to explain cause, and answer the question 'why;' that is, respondents set a standard for reporting individually relevant genetic research results to individual participants that is specific to autism, reflecting the metaphysical value that genetic information is seen to offer in this context. In addition to this standard of meaning, respondents required that results be deemed 'true.' Here, respondents referenced standards of validity that were context nonspecific. Yet in practice, what qualified as 'true' depended on evidentiary standards within specific research disciplines as well as fundamental, and contested, theories about how autism is 'genetic.' For research ethics, these finding suggest that uniform and context-free obligations regarding result disclosure cannot readily be specified. For researchers, they suggest that result disclosure to individuals should be justified not only by perceived meaning but also by clarity regarding appropriate evidentiary standards, and attention to the status of epistemological debates regarding the nature and cause of disorders.

Imagining value, imagining users: academic technology transfer for health innovation.

Governments have invested heavily in the clinical and economic promise of health innovation and express increasing concern with the efficacy and efficiency of the health innovation system. In considering strategies for 'better' health innovation, policy makers and researchers have taken a particular interest in the work of universities and related public research organizations: How do these organizations identify and transfer promising innovations to market, and do these efforts make best use of public sector investments? We conducted an ethnographic study of technology transfer offices (TTOs) in Ontario and British Columbia, Canada, to consider the place of health and health system imperatives in judgments of value in early-stage health innovation. Our analysis suggests that the valuation process is poorly specified as a set of task-specific judgments. Instead, we argue that technology transfer professionals are active participants in the construction of the innovation and assign value by 'imagining' the end product in its 'context of use'. Oriented as they are to the commercialization of health technology, TTOs understand users primarily as market players. The immediate users of TTOs' efforts are commercial partners (i.e., licensees, investors) who are capable of translating current discoveries into future commodities. The ultimate end users - patients, clinicians, health systems - are the future consumers of the products to be sold. Attention to these proximate and more distal users in the valuation process is a complex and constitutive feature of the work of health technology transfer. At the same time, judgements about individual technologies are made in relation to a broader imperative through which TTOs seek to imagine and construct sustainable innovation systems. Judgments of value are rendered sensible in relation to the logic of valuation for systems of innovation that, in turn, configure users of health innovation in systemic ways.

Questioning the consensus: managing carrier status results generated by newborn screening.

An apparent consensus governs the management of carrier status information generated incidentally through newborn screening: results cannot be withheld from parents. This normative stance encodes the focus on autonomy and distaste for paternalism that characterize the principles of clinical bioethics. However, newborn screening is a classic public health intervention in which paternalism may trump autonomy and through which parents are-in effect-required to receive carrier information. In truth, the disposition of carrier results generates competing moral infringements: to withhold information or require its possession. Resolving this dilemma demands consideration of a distinctive body of public health ethics to highlight the moral imperatives associated with the exercise of collective authority in the pursuit of public health benefits.

Contending visions in the evolution of genetic medicine: the case of cancer genetic services in Ontario, Canada.

Growth in genetic medicine has provoked debate about how new and emerging genetic services should be provided, and specifically, what roles non-genetic clinicians should assume. We address this question through a qualitative interview based case study of the program in genetic testing for the hereditary cancer syndromes (breast/ovarian and colorectal) in Ontario, Canada. We argue that two communities offer parallel visions of cancer genetic care: one "genetic," the other "oncologic." Both communities argue from precedent that cancer genetics is a natural extension of their work: it is "what we do." Both communities also highlight the importance of their own expertise in providing core elements of cancer genetic care: it requires "what we know." Further, both communities perceive the need for leadership by their own (or a related) community as genetic medicine expands to include a broader array of more common and complex diseases: it is expanding "where we're leading." Yet, the "we's" articulating these visions are not reducible to professional identity; rather, both represent distinctive "communities of practice and discourse" that are constructed in relation to institutionalized professional roles, and interactions with the genetic technologies (both tests and counselling) themselves. Available literature on the role of diverse health care professionals in the provision of genetic health care presumes a fixed identity and set of approaches for each professional group that might play a role. Further, existing models tend to assume that genetic technologies are given as tools, and that service organization concerns primarily questions of who will have access to these tools and their powers, as well as the consequent professional and ethical responsibilities. Yet questions about who will control genetic technologies are not simply turf battles between the professions: they are also inescapably questions about what the genetic technologies should and will accomplish clinically.

The helix in the labyrinth: do we need genetic health services and policy research?

In Canada and elsewhere, targeted health services and policy research (HSPR) has been suggested as a means to clarify the health system implications of developments in genetics and genomics. But is such research really needed? We argue that substantial investments in basic genetic and genomic research, coupled with persistent uncertainty about the health system implications of advances in these fields, justify the development of specialized HSPR in genetics and the sustained involvement of the wider HSPR community. Genetic health services and policy research will play a crucial role in informing decision-makers at all levels of the health system about whether and how to integrate developments in genetics, genomics and other complex new technologies.

'Your true and proper gender': the Barr body as a good enough science of sex.

In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. This discovery offered an important diagnostic technology to the burgeoning clinical science community engaged with the medical interpretation and management of sexual anomalies. It seemed to offer a way to identify the true, underlying sex in those whose bodies or lives were sexually anomalous (intersexuals, homosexuals and transsexuals). The hypothesis that allowed the Barr body to stand in for 'chromosomal' or 'genetic' sex was provisional, but it supported the expectation that genetic information established one's primary identity, and the conviction that the animal world could be neatly divided into two, and only two, sexes. Ultimately, this provisional hypothesis, and its status as an unambiguous arbiter of true sex, was overturned. But during much of the 1950s, Barr's thesis about the identity of the Barr body was consistent with a coherent set of theories and evidence explaining sexual development and sexual pathology. Though provisional, the scientific status of the sex chromatin within this system of knowledge was good enough to support a flourishing research enterprise in the clinical sciences.

Redefining disease? The nosologic implications of molecular genetic knowledge.

How will developments in genetic knowledge affect the classification of disease? Leaders in genetics have suggested that knowledge of the role of genes in disease can determine nosology. Diseases might be defined by genotype, thus avoiding the limitations of more empirical approaches to categorization. Other commentators caution against disease definitions that are detached from the look and feel of disease, and argue for an interplay between genotypic and phenotypic information. Still others attribute nosologic change to social processes. We draw on an analysis of the scientific literature, our conversations with genetics clinicians, and reviews of patient organization Web sites to offer a revised interpretation of the nosologic implications of molecular genetic knowledge. We review the recent histories of three diseases--hemophilia, Rett syndrome, and cystic fibrosis--to argue that nosologic change cannot be explained by either biologic theories of disease etiology or sociologic theories of social tendencies. Although new genetic information challenges disease classifications and is highly influential in their redesign, genetic information can be used in diverse ways to reconstruct disease categories and is not the only influence in these revisions. Ironically, genetic information is likely to play a central role in producing a new, but still empirical, classification scheme.