Broadening the Debate About Post-trial Access to Medical Interventions: A Qualitative Study of Participant Experiences at the End of a Trial Investigating a Medical Device to Support Type 1 Diabetes Self-Management.

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation.

Lay Perspectives on Receiving Different Types of Genomic Secondary Findings: a Qualitative Vignette Study.

Genome-wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics' perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Our aim was to explore how lay people react to different types of hypothetical genomic SFs. Participants received a hypothetical letter revealing a SF predisposing to a severe but actionable disease-cardiovascular disease (familial hypercholesterolemia, long QT syndrome) or cancer (Lynch syndrome, Li-Fraumeni syndrome). Participants (N = 29) wrote down their initial reactions, and discussed (N = 23) these in focus groups. Data were analyzed using inductive thematic analysis. Reactions to hypothetical SFs varied according to perceived severity and familiarity of the diseases. SFs for cancer were perceived as more threatening than for cardiovascular diseases, but less distressing than risk for psychiatric or neurological disorders, which participants spontaneously brought up. Illness severity in terms of lived experience, availability of treatment, stigma, and individual's responsibility to control risk were perceived to vary across these disease types. In addition to clinical validity and utility, SF reporting practices need to take into account potential familiarity and lay illness representations of different diseases. Illness representations may influence willingness to receive SFs, and individuals' reactions to this information.

"I would like to discuss it further with an expert": a focus group study of Finnish adults' perspectives on genetic secondary findings.

Lowered costs of genomic sequencing facilitate analyzing large segments of genetic data. Ethical debate has focused on whether and what kind of incidental or secondary findings (SFs) to report, and how to obtain valid informed consent. However, people's support needs after receiving SFs have received less attention. We explored Finnish adults' perspectives on reporting genetic SFs. In this qualitative study which included four focus group discussions (N = 23) we used four vignette letters, each reporting a genetic SF predisposing to a different disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li-Fraumeni syndrome. Transcribed focus group discussions were analyzed using inductive thematic analysis. Major themes were immediate shock, dealing with worry and heightened risk, fear of being left alone to deal with SFs, disclosing to family, and identified support needs. Despite their willingness to receive SFs, participants were concerned about being left alone to deal with them. Empathetic expert support and timely access to preventive care were seen as essential to coping with shock and worry, and disclosing SFs to family. Discussion around SFs needs to concern not only which findings to report, but also how healthcare systems need to prepare for providing timely access to preventive care and support for individuals and families.

Written versus verbal consent: a qualitative study of stakeholder views of consent procedures used at the time of recruitment into a peripartum trial conducted in an emergency setting.

BACKGROUND: Obtaining prospective written consent from women to participate in trials when they are experiencing an obstetric emergency is challenging. Alternative consent pathways, such as gaining verbal consent at enrolment followed, later, by obtaining written consent, have been advocated by some clinicians and bioethicists but have received little empirical attention. We explored women's and staff views about the consent procedures used during the internal pilot of a trial (GOT-IT), where the protocol permitted staff to gain verbal consent at recruitment. METHODS: Interviews with staff (n = 27) and participating women (n = 22). Data were analysed thematically and interviews were cross-compared to identify differences and similarities in participants' views about the consent procedures used. RESULTS: Women and some staff highlighted benefits to obtaining verbal consent at trial enrolment, including expediting recruitment and reducing the burden on those left exhausted by their births. However, most staff with direct responsibility for taking consent expressed extreme reluctance to proceed with enrolment until they had obtained written consent, despite being comfortable using verbal procedures in their clinical practice. To account for this resistance, staff drew a strong distinction between research and clinical care and suggested that a higher level of consent was needed when recruiting into trials. In doing so, staff emphasised the need to engage women in reflexive decision-making and highlighted the role that completing the consent form could play in enabling and evidencing this process. While most staff cited their ethical responsibilities to women, they also voiced concerns that the absence of a signed consent form at recruitment could expose them to greater risk of litigation were an individual to experience a complication during the trial. Inexperience of recruiting into peripartum trials and limited availability of staff trained to take consent also reinforced preferences for obtaining written consent at recruitment. CONCLUSIONS: While alternative consent pathways have an important role to play in advancing emergency medicine research, and may be appreciated by potential recruits, they may give rise to unintended ethical and logistical challenges for staff. Staff would benefit from training and support to increase their confidence and willingness to recruit into trials using alternative consent pathways. TRIAL REGISTRATION: This qualitative research was undertaken as part of the GOT-IT Trial (trial registration number: ISCRTN 88609453 ). Date of registration 26/03/2014.

Implementing risk-stratified screening for common cancers: a review of potential ethical, legal and social issues.

BACKGROUND: The identification of common genetic variants associated with common cancers including breast, prostate and ovarian cancers would allow population stratification by genotype to effectively target screening and treatment. As scientific, clinical and economic evidence mounts there will be increasing pressure for risk-stratified screening programmes to be implemented. METHODS: This paper reviews some of the main ethical, legal and social issues (ELSI) raised by the introduction of genotyping into risk-stratified screening programmes, in terms of Beauchamp and Childress's four principles of biomedical ethics--respect for autonomy, non-maleficence, beneficence and justice. Two alternative approaches to data collection, storage, communication and consent are used to exemplify the ELSI issues that are likely to be raised. RESULTS: Ultimately, the provision of risk-stratified screening using genotyping raises fundamental questions about respective roles of individuals, healthcare providers and the state in organizing or mandating such programmes, and the principles, which underpin their provision, particularly the requirement for distributive justice. CONCLUSIONS: The scope and breadth of these issues suggest that ELSI relating to risk-stratified screening will become increasingly important for policy-makers, healthcare professionals and a wide diversity of stakeholders.

Stratified cancer screening: the practicalities of implementation.

BACKGROUND: Improving understanding of the genetic basis of disease susceptibility enables us to estimate individuals' risk of developing cancer and offer them disease prevention, including screening, stratified to reflect that risk. Little attention has so far been given to the implementation of stratified screening. This article reviews the issues that would arise in delivering such tailored approaches to prevention in practice. RESULTS: Issues analysed include the organisational context within which implementation of stratified prevention would occur, how the offer of screening would be made, making sure consent is adequately informed, how individuals' risk would be assessed, the age at which risk estimation should occur, and the potential use of genetic data for other purposes. The review also considers how management might differ depending on individuals' risk, how their results would be communicated and their follow-up arranged, and the different issues raised by modification of an existing screening programme, such as that for breast cancer, and the establishment of a new one, for example for prostate cancer. CONCLUSION: Stratified screening based on genetic testing is a radically new approach to prevention. Various organisational issues would need to be considered before it could be introduced, and a number of questions require further research.

Participants' experiences of intensifying insulin therapy during the Treating to Target in Type 2 Diabetes (4-T) trial: qualitative interview study.

AIM: To explore participants' experiences of intensifying insulin therapy during the Treating to Target in Type 2 Diabetes (4-T) trial. METHODS: In-depth interviews were conducted with 41 trial participants who had had their insulin therapy intensified during this trial. Data were analysed using an inductive, thematic approach. RESULTS: The vast majority of participants were receptive towards intensifying treatment. Whilst some were happy simply to follow health professionals' recommendations, others saw taking two types of insulin as a more effective way of controlling their diabetes. Post-intensification, participants sought to remember to take their additional injections by developing injection-related strategies and daily routines. The need to inject insulin whilst in public often arose more frequently following intensification and was a consistent source of anxiety. Those who were worried about injecting in public sought to avoid having to do so; for example, by injecting in toilets or by advancing or delaying the timing of their injections. CONCLUSIONS: IT was not increasing the number of daily injections per se which was problematic for the participants who had agreed to have their insulin therapies intensified, but the increased likelihood of having to inject insulin in public. Addressing concerns about injecting in public places may help promote adherence to intensified insulin regimens.

An investigation of patients' motivations for their participation in genetics-related research.

DESIGN: Qualitative interview study. PARTICIPANTS: Fifty-nine patients with a family history of cancer who attend a regional cancer genetics clinic in the UK were interviewed about their current and previous research experiences. FINDINGS: Interviewees gave a range of explanations for research participation. These were categorised as (a) social--research participation benefits the wider society by progressing science and improving treatment for everyone; (b) familial--research participation may improve healthcare and benefit current or future generations of the participant's family; and (c) personal--research participation provides therapeutic or non-therapeutic benefits for oneself. CONCLUSIONS: We discuss the distinction drawn between motives for research participation focused upon self (personal) and others (familial/social), and observe that personal, social and familial motives can be seen as interdependent. For example, research participation that is undertaken to benefit others, particularly relatives, may also offer a number of personal benefits for self, such as enabling participants to feel that they have discharged their social or familial obligations. We argue for the need to move away from simple, static, individualised notions of research participation to a more complex, dynamic and inherently social account.

Treatment-focused DNA testing for newly diagnosed breast cancer patients: some implications for clinical practice.

There is accumulating evidence that women with breast cancer due to a familial BRCA1 or BRCA2 mutation benefit from specific surgical and chemotherapeutic treatment strategies. However, the rapid identification of such patients during the acute phase of treatment raises a number of issues. This study investigated Australian opinion leaders' views on the issues arising from such 'treatment-focused' genetic testing. Semi-structured interviews with 34 opinion leaders working in cancer genetics were undertaken. Interviewees acknowledged the introduction of treatment-focused DNA testing has the potential to positively transform the management of breast cancer patients, but were concerned that certain ethical and logistical issues have yet to be addressed. These include decision-making and consent, the familial nature of genetic information, and the management of genetics services within familial cancer clinics in the public hospital system in Australia. Service providers will need to have policies and strategies for managing the increased demand. It will also be necessary to include genetic counseling services within familial cancer clinics in the care pathway for newly diagnosed patients prior to any DNA testing to determine adjuvant treatment; such services may be more cost-effective than expecting surgeons and medical oncologists to fulfill this role.

Healthcare professionals' and researchers' understanding of cancer genetics activities: a qualitative interview study.

AIMS: To describe individuals' perceptions of the activities that take place within the cancer genetics clinic, the relationships between these activities and how these relationships are sustained. DESIGN: Qualitative interview study. PARTICIPANTS: Forty individuals involved in carrying out cancer genetics research in either a clinical (n = 28) or research-only (n = 12) capacity in the UK. FINDINGS: Interviewees perceive research and clinical practice in the subspecialty of cancer genetics as interdependent. The boundary between research and clinical practice is described as vague or blurred, and this ambiguity is regarded as being sustained by a range of methodological, ethical and economic factors. The implications of these findings for the "therapeutic misconception" are explored. It is argued that while research participation is seen as having therapeutic benefit for individual patients, the interviewees are not labouring under any misconceptions about the relationship between research and clinical care. It is suggested that concepts such as the "therapeutic misconception" may have less relevance in highly technological specialities that are characterised by a developing evidence base.

Genetic research on rare familial disorders: consent and the blurred boundaries between clinical service and research.

OBJECTIVES: To study the consent process experienced by participants who are enrolled in a molecular genetic research study that aims to find new genetic mutations responsible for an apparently inherited disorder. DESIGN: Semi-structured interviews and analysis/description of main themes. PARTICIPANTS: 78 members of 52 families who had been recruited to a molecular genetic study. RESULTS: People were well informed about the goals, risks and benefits of the genetic research study but could not remember the consent process. They had mostly been recruited to take part by trusted clinicians or their relatives but had little memory of, or concern about signing consent forms. Families appeared to regard the research as a continuation of their, or their relatives', clinical care. CONCLUSIONS: Ethical review should be more flexible in its attitude to consent forms and written information sheets for some sorts of research. For rare genetic disease studies where research has been discussed fully within the clinical setting then the consent obtained at that time could suffice rather than needing extra consent at a later stage. However, clinician-researchers will need to ensure that their duty of care extends for the duration of the research and beyond.

Diabetes service provision: a qualitative study of the experiences and views of Pakistani and Indian patients with Type 2 diabetes.

AIMS: To explore Pakistani and Indian patients' experiences of, and views about, diabetes services in order to inform the development of culturally sensitive services. DESIGN: Qualitative, interview study involving 23 Pakistani and nine Indian patients with Type 2 diabetes recruited from general practices and the local community in Edinburgh, Scotland. Data collection and analysis occurred concurrently and recruitment continued until no new themes emerged from the interviews. RESULTS: Respondents expressed gratitude for the availability of free diabetes services in Britain, as they were used to having to pay to access health care on the Indian subcontinent. Most looked to services for the prompt detection and treatment of complications, rather than the provision of advice about managing their condition. As respondents attached importance to receiving physical examinations, they could be disappointed when these were not offered by health-care professionals. They disliked relying on interpreters and identified a need for bilingual professionals with whom they could discuss their diabetes care directly. CONCLUSIONS: Gratitude for free services in Britain may instil a sense of indebtedness which makes it difficult for Pakistanis and Indians to be critical of their diabetes care. Health-care professionals may need to describe their roles carefully, and explain how different diabetes services fit together, to avoid Pakistani and Indian patients perceiving treatment as unsatisfactory. Whilst linkworker schemes may meet patients' need to receive culturally sensitive information in their first language, work is needed to assess their effectiveness and sustainability.

'I can't do any serious exercise': barriers to physical activity amongst people of Pakistani and Indian origin with Type 2 diabetes.

Type 2 diabetes is at least 4 times more common among British South Asians than in the general population. South Asians also have a higher risk of diabetic complications, a situation which has been linked to low levels of physical activity observed amongst this group. Little is known about the factors and considerations which prohibit and/or facilitate physical activity amongst South Asians. This qualitative study explored Pakistani (n = 23) and Indian (n = 9) patients' perceptions and experiences of undertaking physical activity as part of their diabetes care. Although respondents reported an awareness of the need to undertake physical activity, few had put this lifestyle advice into practice. For many, practical considerations, such as lack of time, were interwoven with cultural norms and social expectations. Whilst respondents reported health problems which could make physical activity difficult, these were reinforced by their perceptions and understandings of their diabetes, and its impact upon their future health. Education may play a role in physical activity promotion; however, health promoters may need to work with, rather than against, cultural norms and individual perceptions. We recommend a realistic and culturally sensitive approach, which identifies and capitalizes on the kinds of activities patients already do in their everyday lives.

Men's decision-making about predictive BRCA1/2 testing: the role of family.

Men who have a family history of breast and/or ovarian cancer may be offered a predictive genetic test to determine whether or not they carry the family specific BRCA1/2 mutation. Male carriers may be at increased risk of breast and prostate cancers. Relatively little is known about at-risk men's decision-making about BRCA1/2 testing. This qualitative study explores the influences on male patients' genetic test decisions. Twenty-nine in-depth interviews were undertaken with both carrier and noncarrier men and immediate family members (17 male patients, 8 female partners, and 4 adult children). These explored family members' experiences of cancer and genetic testing, decision-making about testing, family support, communication of test results within the family, risk perception and risk management. Implicit influences on men's testing decisions such as familial obligations are examined. The extent to which other family members--partners and adult children--were involved in testing decisions is also described. It is demonstrated that mothers of potential mutation carriers not only perceive themselves as having a right to be involved in making this decision, but also were perceived by their male partners as having a legitimate role to play in decision-making. There was evidence that (adult) children were excluded from the decision-making, and some expressed resentment about this. The implications of these findings for the practice of genetic counseling are discussed.

Communication about genetic testing in families of male BRCA1/2 carriers and non-carriers: patterns, priorities and problems.

This qualitative interview study explored the way in which information about predictive BRCA1/2 testing and its implications for children is disseminated within the families of at-risk men who undergo genetic testing. Twenty-nine in-depth interviews were carried out with family members [male patients (n = 17), their partners (n = 8) and adult children (n = 4)]. These explored the following themes: experiences of cancer and genetic testing, decision-making about testing and the communication of test results and genetic information within the immediate family. The interviews revealed that both male patients and their partners perceive themselves, rather than health professionals, as responsible for disclosing information about genetic testing and genetic risks to their children. Parents described three different communication strategies for the disclosure of genetic information to their children: complete openness, limited disclosure and total secrecy. The adoption of a particular communication strategy was justified in terms of children's rights to information vs their parental duties to protect their children from anxiety-provoking information. Some of the problems arising from the adoption of different disclosure patterns are identified and the implications for clinical practice are discussed.

Accommodating risk: responses to BRCA1/2 genetic testing of women who have had cancer.

The relationship between risk awareness and anxiety has been the subject of extensive theoretical debate and empirical research. Previous studies of women with a family history of hereditary breast and ovarian cancer suggest that both healthy at-risk women and former cancer patients report increased anxiety upon learning about their increased risks of developing these diseases. Indeed, anxiety about genetic risks has been reported as influencing decisions about DNA-testing and risk-reducing surgery on healthy breasts and ovaries. This qualitative study of women who had been treated for breast/ovarian cancer investigated their perceptions of, and reactions to, their genetic risks of developing further cancers following genetic testing (BRCA1/2 mutation searching). In-depth interviews were undertaken with 30 women (10 mutation carriers, 8 awaiting a result and 12 who received an inconclusive test result). Whilst the majority of women in all three groups adopted a fatalistic approach with regard to their future health and did not regard their genetic risks as a threat to self, a few reported heightened anxiety on learning they were at increased risk of developing a second primary cancer. The data suggest that affected women understand their genetic risks of cancer within the context of their previous disease experiences. It is observed that women's responses to their genetic risk are influenced by the degree to which they have accommodated their risk status in their biography following their diagnosis and treatment of cancer.

Balancing autonomy and responsibility: the ethics of generating and disclosing genetic information.

Using data obtained during a retrospective interview study of 30 women who had undergone genetic testing-BRCA1/2 mutation searching-this paper describes how women, previously diagnosed with breast/ovarian cancer, perceive their role in generating genetic information about themselves and their families. It observes that when describing their motivations for undergoing DNA testing and their experiences of disclosing genetic information within the family these women provide care based ethical justifications for their actions. Finally, it argues that generating genetic information and disclosing this information to kin raise different types of ethical issues. The implications of these findings for ethical debates about informed choice in the context of genetic testing are discussed.

Genetic testing for women previously diagnosed with breast/ovarian cancer: examining the impact of BRCA1 and BRCA2 mutation searching.

This study sought to investigate the impact of BRCA1 and BRCA2 mutation searching on women previously diagnosed with breast or ovarian cancer. In-depth interviews were undertaken with 30 women who had undergone a BRCA1 and BRCA2 mutation search within the clinical setting. The main reasons reported for undergoing mutation searching were: to provide genetic information for other family members, general altruism, curiosity about the aetiology of cancer, and to provide information to facilitate risk management decisions. In the main, the process of undergoing genetic testing was not experienced as anxiety provoking. The benefit of receiving a result confirming the presence of a genetic mutation was seen as an end to uncertainty, whereas the costs included difficulties in disclosing information to kin and potentially increased anxiety about one's own or others' cancer risks. Women receiving an inconclusive test result reported a range of emotional reactions. There was evidence that some women misunderstood the meaning of this result, interpreting it as definitive confirmation that a cancer-predisposing mutation was not present within the family. It is concluded that women with cancer who participate in BRCA1 and BRCA2 testing need to receive clear information about the meaning and implications of the different types of test results. Some recommendations for clinical practice are discussed.

A qualitative study of the information needs of high-risk women undergoing prophylactic oophorectomy.

This qualitative study sought to determine the information needs of high-risk pre-menopausal women who had undergone prophylactic bilateral oophorectomy to manage their inherited risk of ovarian cancer. In-depth interviews were carried out with 23 high-risk women following surgery. Although the benefit of risk reduction was perceived as out weighing the costs of surgery, many women reported that they would have liked more information about the physical and emotional after-effects of oophorectomy prior to and following surgery. The analysis identified five different types of information needed by women making surgical decisions, comprising information about ovarian function and the menopause, hormone replacement therapy (HRT), surgical procedures, convalescence and the risk of inheriting a genetic mutation and developing cancer. It is suggested that, in addition to genetic counselling for hereditary ovarian cancer, women should receive information about both the costs and benefits of prophylactic oophorectomy, and should have access to gynaecology nurse specialists both before and after surgery.