Facilitating the ethical sourcing of donor hematopoietic stem cells for cell and gene therapy research and development.

Aim: Unrelated stem cell donor registries (DRs) are increasingly engaging in the field of cell and gene therapy (CGT). This study aims to explore the values, concerns, needs and expectations of donors and members of the public on donating hematopoietic stem cells (HSCs) for CGT. Methods: Seven focus groups were conducted in 2019 with members of the public, prospective donors and donors on the Anthony Nolan DR in the UK. Results: Participants expressed concerns over increased frequency of donation and incidental findings and required more information on the type of research including the purpose and possible outcomes. Conclusion: Addressing donors' concerns, needs and expectations on donating cellular materials for CGT research and development is essential to maintaining the highest standards for donor care and safety within this rapidly emerging field.

This study aims to explore the values, concerns, needs and expectations of people who donate, or consider donating, their stem cells (cells that can develop into many different types of cells) for research that could lead to new medical treatments. We focused on the thoughts of these donors about providing their cells for use in cell and gene therapy (CGT) research, a field that is rapidly advancing but still forming its rules and ethical guidelines. In 2019, we conducted seven focus groups (FGs) with a total of 73 people in the UK. This included individuals who are registered as potential stem cell donors on the Anthony Nolan unrelated stem cell donor register (DR), those who have already donated stem cells and members of the general public. We explored their thoughts about their donated cells being used for research to develop new therapies rather than for direct treatment of patients. Questions during the FGs touched on topics such as the roles of various organizations in managing donated cells, the commercial use of these cells and where responsibilities lie in ensuring ethical practices. Participants expressed a strong desire for openness and clear communication regarding how their donated cells are used in research. They wanted to ensure that any use of their cells aligns with their personal values and the ethical standards of the organizations handling the donations. Participants expected DRs like Anthony Nolan to safeguard their interests and the ethical use of their cells. This study highlights that while donors are generally willing to contribute to advancements in CGT research, they need clear, understandable information about how their donations are used. This is crucial for maintaining their trust and willingness to donate. Overall, this study underscores the importance of ethical practices and donor engagement in the growing field of CGT, ensuring that donor contributions are respected and used responsibly.

Gender, flexibility and workforce in the NHS: A qualitative study.

Data from the General Medical Council show that the number of female doctors registered to practise in the UK continues to grow at a faster rate than the number of male doctors. Our research critically discusses the impact of this gender-based shift, considering how models of medical training are still ill-suited to supporting equity and inclusivity within the workforce, with particular impacts for women despite this gender shift. Drawing on data from our research project Mapping underdoctored areas: the impact of medical training pathways on NHS workforce distribution and health inequalities, this paper explores the experiences of doctors working in the NHS, considering how policies around workforce and beyond have impacted people's willingness and ability to continue in their chosen career path. There is clear evidence that women are underrepresented in some specialties such as surgery, and at different career stages including in senior leadership roles, and our research focuses on the structural factors that contribute to reinforcing these under-representations. Medical education and training are known to be formative points in doctors' lives, with long-lasting impacts for NHS service provision. By understanding in detail how these pathways inadvertently shape where doctors live and work, we will be able to consider how best to change existing systems to provide patients with timely and appropriate access to healthcare. We take a cross-disciplinary theoretical approach, bringing historical, spatiotemporal and sociological insights to healthcare problems. Here, we draw on our first 50 interviews with practising doctors employed in the NHS in areas that struggle to recruit and retain doctors, and explore the gendered nature of career biographies. We also pay attention to the ways in which doctors carve their own career pathways out of, or despite of, personal and professional disruptions.

Unsettling the treatment imperative? Chemotherapy decision-making in the wake of genomic techniques.

Social scientists have argued that a treatment imperative shapes experiences of biomedicine. This is evident within oncology, where discourses of hope are tempered by persistent fears surrounding cancer. It is within this context that genomic decision-making tools are entering routine care. These may indicate that a treatment is not appropriate for a particular disease profile. We draw on qualitative interviews and observations centred on gene expression profiling to consider the implications of this technique for the treatment imperative in early breast cancer. Influenced by sociological perspectives on medical technologies, we discuss how fallibilities of established tools have forged a space for the introduction of genomic testing into chemotherapy decision-making. We demonstrate how high expectations shaped patients' interpretations of this tool as facilitating the 'right' treatment choice. We then unpick these accounts, highlighting the complex relationship between gene expression profiling and treatment decision-making. We argue that anticipations for genomic testing to provide certainty in treatment choice must account for the sociocultural and organisational contexts in which it is used, including the powerful entwinement of chemotherapy and cancer. Our research has implications for sociological perspectives on treatment decision-making and clinical expectations for genomic medicine to resolve the 'problem' of overtreatment.

Accessing targeted therapies for cancer: self and collective advocacy alongside and beyond mainstream cancer charities.

As precision oncology has evolved, patients and their families have become more involved in efforts to access these treatments via fundraising and campaigning that take place outside of the larger cancer charities. In this paper, we explore the solidarities, networks, and emotional work of the UK-based access advocates, drawing on the stories of nine advocates, which included interviews and content analyses of their social media posts and coverage of their case in news, commentary, and fundraising websites. We consider the emotional and knowledge work of building networks that spanned consumerist and activist agendas, forged individual and collective goals, and orientations toward the public, private, and third sectors as part of securing support and access. Through these various practices, the actors we have studied cultivated personal advantage and solidarities with other patients and advocates, and in so doing engaged in self and collective advocacy alongside and beyond mainstream cancer charities.

Diagnostic layering: Patient accounts of breast cancer classification in the molecular era.

Social scientific work has considered the promise of genomic medicine to transform healthcare by personalising treatment. However, little qualitative research attends to already well-established molecular techniques in routine care. In this article we consider women's experiences of routine breast cancer diagnosis in the UK NHS. We attend to patient accounts of the techniques used to subtype breast cancer and guide individual treatment. We introduce the concept of 'diagnostic layering' to make sense of how the range of clinical techniques used to classify breast cancer shape patient experiences of diagnosis. The process of diagnostic layering, whereby various levels of diagnostic information are received by patients over time, can render diagnosis as incomplete and subject to change. In the example of early breast cancer, progressive layers of diagnostic information are closely tied to chemotherapy recommendations. In recent years a genomic test, gene expression profiling, has become introduced into routine care. Because gene expression profiling could indicate a treatment recommendation where standard tools had failed, the technique could represent a 'final layer' of diagnosis for some patients. However, the test could also invalidate previous understandings of the cancer, require additional interpretation and further prolong the diagnostic process. This research contributes to the sociology of diagnosis by outlining how practices of cancer subtyping shape patient experiences of breast cancer. We add to social scientific work attending to the complexities of molecular and genomic techniques by considering the blurring of diagnostic and therapeutic activities from a patient perspective.

Accomplishing an adaptive clinical trial for cancer: Valuation practices and care work across the laboratory and the clinic.

A new generation of adaptive, multi-arm clinical trials has been developed in cancer research including those offering experimental treatments to patients based on the genomic analysis of their cancer. Depending on the molecular changes found in patients' cancer cells, it is anticipated that targeted and personalised therapies will be made available for those who have reached the end of standard treatment options, potentially extending survival time. Results from these trials are also expected to advance genomic knowledge for patients in the future. Drawing on data from a qualitative study of one such trial in the UK, comprising observations of out-patient clinic appointments, out-patient biopsy procedures, laboratory work, and interviews with practitioners, this paper explores how the clinical and research value of one such trial was accomplished in everyday practice by focussing on the work of clinical trials and laboratory staff across recruitment, laboratory analysis, and results management. In the face of numerous potential set-backs, disappointments and failure, we explore how practitioners worked to balance the need to meet established measures of value such as numbers of patients recruited into the trial, alongside cultivating the value of positive affects for patients by managing their expectations and emotions. This care work was performed primarily by practitioners whose roles have historically been devalued in healthcare practice and yet, as we show, were critical to this process. We conclude by arguing that as complex multi-arm adaptive trials become more commonplace, we need to attend to, and render visible, the dynamic and care-full valuation practices of backstage practitioners through which experimental biomedicine is accomplished, and in doing so show that care both achieves clinical and research value, and is also a series of practices and processes that tends to tissue, patients and staff in the context of ever-present possibility of failure.

Genomic research and the cancer clinic: uncertainty and expectations in professional accounts.

This paper explores clinicians' and scientists' accounts of genomic research in cancer care and the complexities and challenges involved with delivering this work. Contributing to the sociology of (low) expectations, we draw on sociological studies of uncertainty in medicine to explore their accounts of working with uncertainty as part of the management of patient and institutional expectations. We consider their appeals to the importance of modest inquiry and framing of the uncertainties of genomic medicine as normal and at times welcome as they sought to configure professional autonomy and jurisdictions and cultivate an experimental ethos amongst their patients. We argue that these types of uncertainty work [Star, S. L. 1985. "Scientific Work and Uncertainty." Social Studies of Science 15 (3): 391-427] are a key feature of managing expectations at the intersections of genomic research and clinical care.

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).