Providing recurrence risk counselling for parents after diagnosis of a serious genetic condition caused by an apparently de novo mutation in their child: a qualitative investigation of the PREGCARE strategy with UK clinical genetics practitioners.

BACKGROUND: Diagnosis of a child with a genetic condition leads to parents asking whether there is a risk the condition could occur again with future pregnancies. If the cause is identified as an apparent de novo mutation (DNM), couples are currently given a generic, population average, recurrence risk of ~1%-2%, depending on the condition. Although DNMs usually arise as one-off events, they can also originate through the process of mosaicism in either parent; in this instance, the DNM is present in multiple germ cells and the actual recurrence risk could theoretically be as high as 50%. METHODS: Our qualitative interview study examined the views and reflections on current practice provided by UK practitioners working in clinical genetics (n=20) regarding the potential impact of PREcision Genetic Counselling And REproduction (PREGCARE)-a new preconception personalised recurrence risk assessment strategy. RESULTS: Those interviewed regarded PREGCARE as a very useful addition to risk management, especially for cases where it revised the risk downwards or clarified that a couple's personalised recurrence risk meets National Health Service thresholds for non-invasive prenatal testing, otherwise inaccessible based on the generic DNM recurrence risk. CONCLUSION: Participants said it could release some couples requiring reassurance from undergoing unnecessary invasive testing in future pregnancies. However, they regarded mosaicism and PREGCARE as complex concepts to communicate, requiring further training and additional appointment time for pre-test genetic counselling to prepare couples for all the possible outcomes of a personalised risk assessment, including potentially identifying the parental origin of the DNM, and to ensure informed consent.

Germline mismatch repair (MMR) gene analyses from English NHS regional molecular genomics laboratories 1996-2020: development of a national resource of patient-level genomics laboratory records.

OBJECTIVE: To describe national patterns of National Health Service (NHS) analysis of mismatch repair (MMR) genes in England using individual-level data submitted to the National Disease Registration Service (NDRS) by the NHS regional molecular genetics laboratories. DESIGN: Laboratories submitted individual-level patient data to NDRS against a prescribed data model, including (1) patient identifiers, (2) test episode data, (3) per-gene results and (4) detected sequence variants. Individualised per-laboratory algorithms were designed and applied in NDRS to extract and map the data to the common data model. Laboratory-level MMR activity audit data from the Clinical Molecular Genetics Society/Association of Clinical Genomic Science were used to assess early years' missing data. RESULTS: Individual-level data from patients undergoing NHS MMR germline genetic testing were submitted from all 13 English laboratories performing MMR analyses, comprising in total 16 722 patients (9649 full-gene, 7073 targeted), with the earliest submission from 2000. The NDRS dataset is estimated to comprise >60% of NHS MMR analyses performed since inception of NHS MMR analysis, with complete national data for full-gene analyses for 2016 onwards. Out of 9649 full-gene tests, 2724 had an abnormal result, approximately 70% of which were (likely) pathogenic. Data linkage to the National Cancer Registry demonstrated colorectal cancer was the most frequent cancer type in which full-gene analysis was performed. CONCLUSION: The NDRS MMR dataset is a unique national pan-laboratory amalgamation of individual-level clinical and genomic patient data with pseudonymised identifiers enabling linkage to other national datasets. This growing resource will enable longitudinal research and can form the basis of a live national genomic disease registry.

Ethical preparedness in genomic medicine: how NHS clinical scientists navigate ethical issues.

Much has been published about the ethical issues encountered by clinicians in genetics/genomics, but those experienced by clinical laboratory scientists are less well described. Clinical laboratory scientists now frequently face navigating ethical problems in their work, but how they should be best supported to do this is underexplored. This lack of attention is also reflected in the ethics tools available to clinical laboratory scientists such as guidance and deliberative ethics forums, developed primarily to manage issues arising within the clinic.We explore what ethical issues are being experienced by clinical scientists, how they think such issues could be best analysed and managed, and whether their practice might be enhanced by more situated approaches to ethics deliberation and practice such as ethical preparedness. From thematic analysis of cases presented by clinical scientists at a specially convened meeting of the UK Genethics Forum, we derived three main ethical themes: (1) the redistribution of labour and responsibilities resulting from the practice of genomic medicine; (2) the interpretation and certainty of results and (3) the proposal that better standardisation and consistency of ethical approaches (for example, more guidelines and policy) could resolve some of the challenges arising.We argue that although standardisation is important for promoting shared understandings of good (including ethical) practice, supplementary approaches to enhance and sustain ethical preparedness will be important to help clinical scientists and others in the recently expanded genetic/genomic medicine environment foster quality ethical thinking.

Professionals' views on providing personalized recurrence risks for de novo mutations: Implications for genetic counseling.

When an apparent de novo (new) genetic change has been identified as the cause of a serious genetic condition in a child, many couples would like to know the risk of this happening again in a future pregnancy. Current practice provides families with a population average risk of 1%-2%. However, this figure is not accurate for any specific couple, and yet, they are asked to make decisions about having another child and/or whether to have prenatal testing. The PREcision Genetic Counseling And REproduction (PREGCARE) study is a new personalized assessment strategy that refines a couple's recurrence risk prior to a new pregnancy, by analyzing several samples from the parent-child trio (blood, saliva, swabs, and father's sperm) using deep sequencing and haplotyping. Overall, this approach can reassure ~2/3 of couples who have a negligible (<0.1%) recurrence risk and focus support on those at higher risk (i.e. when mosaicism is identified in one of the parents). Here we present a qualitative interview study with UK clinical genetics professionals (n = 20), which investigate the potential implications of introducing such a strategy in genetics clinics. While thematic analysis of the interviews indicated perceived clinical utility, it also indicates a need to prepare couples for the psychosocial implications of parent-of-origin information and to support their understanding of the assessment being offered. When dealing with personalized reproductive risk, a traditional non-directive approach may not meet the needs of practitioner and client(s) and shared decision-making provides an additional framework that may relieve some patient burden. Further qualitative investigation with couples is planned.

Artificial intelligence and medical research databases: ethical review by data access committees.

BACKGROUND: It has been argued that ethics review committees-e.g., Research Ethics Committees, Institutional Review Boards, etc.- have weaknesses in reviewing big data and artificial intelligence research. For instance, they may, due to the novelty of the area, lack the relevant expertise for judging collective risks and benefits of such research, or they may exempt it from review in instances involving de-identified data. MAIN BODY: Focusing on the example of medical research databases we highlight here ethical issues around de-identified data sharing which motivate the need for review where oversight by ethics committees is weak. Though some argue for ethics committee reform to overcome these weaknesses, it is unclear whether or when that will happen. Hence, we argue that ethical review can be done by data access committees, since they have de facto purview of big data and artificial intelligence projects, relevant technical expertise and governance knowledge, and already take on some functions of ethical review. That said, like ethics committees, they may have functional weaknesses in their review capabilities. To strengthen that function, data access committees must think clearly about the kinds of ethical expertise, both professional and lay, that they draw upon to support their work. CONCLUSION: Data access committees can undertake ethical review of medical research databases provided they enhance that review function through professional and lay ethical expertise.

The impact of artificial intelligence on the person-centred, doctor-patient relationship: some problems and solutions.

Artificial intelligence (AI) is often cited as a possible solution to current issues faced by healthcare systems. This includes the freeing up of time for doctors and facilitating person-centred doctor-patient relationships. However, given the novelty of artificial intelligence tools, there is very little concrete evidence on their impact on the doctor-patient relationship or on how to ensure that they are implemented in a way which is beneficial for person-centred care.Given the importance of empathy and compassion in the practice of person-centred care, we conducted a literature review to explore how AI impacts these two values. Besides empathy and compassion, shared decision-making, and trust relationships emerged as key values in the reviewed papers. We identified two concrete ways which can help ensure that the use of AI tools have a positive impact on person-centred doctor-patient relationships. These are (1) using AI tools in an assistive role and (2) adapting medical education. The study suggests that we need to take intentional steps in order to ensure that the deployment of AI tools in healthcare has a positive impact on person-centred doctor-patient relationships. We argue that the proposed solutions are contingent upon clarifying the values underlying future healthcare systems.

"I don't think people are ready to trust these algorithms at face value": trust and the use of machine learning algorithms in the diagnosis of rare disease.

BACKGROUND: As the use of AI becomes more pervasive, and computerised systems are used in clinical decision-making, the role of trust in, and the trustworthiness of, AI tools will need to be addressed. Using the case of computational phenotyping to support the diagnosis of rare disease in dysmorphology, this paper explores under what conditions we could place trust in medical AI tools, which employ machine learning. METHODS: Semi-structured qualitative interviews (n = 20) with stakeholders (clinical geneticists, data scientists, bioinformaticians, industry and patient support group spokespersons) who design and/or work with computational phenotyping (CP) systems. The method of constant comparison was used to analyse the interview data. RESULTS: Interviewees emphasized the importance of establishing trust in the use of CP technology in identifying rare diseases. Trust was formulated in two interrelated ways in these data. First, interviewees talked about the importance of using CP tools within the context of a trust relationship; arguing that patients will need to trust clinicians who use AI tools and that clinicians will need to trust AI developers, if they are to adopt this technology. Second, they described a need to establish trust in the technology itself, or in the knowledge it provides-epistemic trust. Interviewees suggested CP tools used for the diagnosis of rare diseases might be perceived as more trustworthy if the user is able to vouchsafe for the technology's reliability and accuracy and the person using/developing them is trusted. CONCLUSION: This study suggests we need to take deliberate and meticulous steps to design reliable or confidence-worthy AI systems for use in healthcare. In addition, we need to devise reliable or confidence-worthy processes that would give rise to reliable systems; these could take the form of RCTs and/or systems of accountability transparency and responsibility that would signify the epistemic trustworthiness of these tools. words 294.

Taking it to the bank: the ethical management of individual findings arising in secondary research.

A rapidly growing proportion of health research uses 'secondary data': data used for purposes other than those for which it was originally collected. Do researchers using secondary data have an obligation to disclose individual research findings to participants? While the importance of this question has been duly recognised in the context of primary research (ie, where data are collected from participants directly), it remains largely unexamined in the context of research using secondary data. In this paper, we critically examine the arguments for a moral obligation to disclose individual research findings in the context of primary research, to determine if they can be applied to secondary research. We conclude that they cannot. We then propose that the nature of the relationship between researchers and participants is what gives rise to particular moral obligations, including the obligation to disclose individual results. We argue that the relationship between researchers and participants in secondary research does not generate an obligation to disclose. However, we also argue that the biobanks or data archives which collect and provide access to secondary data may have such an obligation, depending on the nature of the relationship they establish with participants.

Nitroglycerin for treatment of retained placenta: A randomised, placebo-controlled, multicentre, double-blind trial in the UK.

BACKGROUND: Retained placenta following vaginal delivery is a major cause of postpartum haemorrhage. Currently, the only effective treatments for a retained placenta are the surgical procedures of manual removal of placenta (MROP) and uterine curettage, which are not universally available, particularly in low- and middle-income countries. The objective of the trial was to determine whether sublingual nitroglycerin spray was clinically effective and cost-effective for medical treatment of retained placenta following vaginal delivery. METHODS AND FINDINGS: A randomised, placebo-controlled, double-blind trial was undertaken between October 2014 and July 2017 at 29 delivery units in the UK (Edinburgh, Glasgow, Manchester, Newcastle, Preston, Warrington, Chesterfield, Crewe, Durham, West Middlesex, Aylesbury, Furness, Southampton, Bolton, Sunderland, Oxford, Nottingham [2 units], Burnley, Chertsey, Stockton-on-Tees, Middlesborough, Chester, Darlington, York, Reading, Milton Keynes, Telford, Frimley). In total, 1,107 women with retained placenta following vaginal delivery were recruited. The intervention was self-administered 2 puffs of sublingual nitroglycerin (800 µg; intervention, N = 543) or placebo spray (control, N = 564). The primary clinical outcome was the need for MROP, assessed at 15 minutes following administration of the intervention. Analysis was based on the intention-to-treat principle. The primary safety outcome was measured blood loss between study drug administration and transfer to the postnatal ward or other clinical area. The primary patient-sided outcomes were satisfaction with treatment and side-effect profile, assessed by questionnaires pre-discharge and 6 weeks post-delivery. Secondary clinical outcomes were measured at 5 and 15 minutes after study drug administration and prior to hospital discharge. There was no statistically significant or clinically meaningful difference in need for MROP by 15 minutes (primary clinical outcome, 505 [93.3%] for nitroglycerin versus 518 [92.0%] for placebo, odds ratio [OR] 1.01 [95% CI 0.98-1.04], p = 0.393) or blood loss (<500 ml: nitroglycerin, 238 [44.3%], versus placebo, 249 [44.5%]; 500 ml-1,000 ml: nitroglycerin, 180 [33.5%], versus placebo, 224 [40.0%]; >1,000 ml: nitroglycerin, 119 [22.2%], versus placebo, 87 [15.5%]; ordinal OR 1.14 [95% CI 0.88-1.48], p = 0.314) or satisfaction with treatment (nitroglycerin, 288 [75.4%], versus placebo, 303 [78.1%]; OR 0.87 [95% CI 0.62-1.22], p = 0.411) or health service costs (mean difference [£] 55.3 [95% CI -199.20 to 309.79]). Palpitations following drug administration were reported more often in the nitroglycerin group (36 [9.8%] versus 15 [4.0%], OR 2.60 [95% CI 1.40-4.84], p = 0.003). There were 52 serious adverse events during the trial, with no statistically significant difference in likelihood between groups (nitroglycerin, 27 [5.0%], versus placebo, 26 [4.6%]; OR 1.13 [95% CI 0.54-2.38], p = 0.747). The main limitation of our study was the low return rate for the 6-week postnatal questionnaire. There were, however, no differences in questionnaire return rates between study groups or between women who did and did not have MROP, with the patient-reported use of outpatient and primary care services at 6 weeks accounting for only a small proportion (approximately 5%) of overall health service costs. CONCLUSIONS: In this study, we found that nitroglycerin is neither clinically effective nor cost-effective as a medical treatment for retained placenta, and has increased side effects, suggesting it should not be used. Further research is required to identify an effective medical treatment for retained placenta to reduce the morbidity caused by this condition, particularly in low- and middle-income countries where surgical management is not available. TRIAL REGISTRATION: ISRCTN.com ISRCTN88609453 ClinicalTrials.gov NCT02085213.

Delivering genomic medicine in the United Kingdom National Health Service: a systematic review and narrative synthesis.

PURPOSE: We sought to assess the readiness of the United Kingdom (UK) National Health Service to implement a Genomic Medicine Service. We conducted a systematic literature review to identify what is known about factors related to the implementation of genomic medicine in routine health care and to draw out the implications for the UK and other settings. METHODS: Relevant studies were identified in Web of Science and PubMed from their date of inception to April 2018. The review included primary research studies using quantitative, qualitative, or mixed methods, and systematic reviews. A narrative synthesis was conducted. RESULTS: Fifty-five studies met our inclusion criteria. The majority of studies reviewed were conducted in the United States. We identified four domains: (1) systems, (2) training and workforce needs, (3) professional attitudes and values, and (4) the role of patients and the public. CONCLUSION: Mainstreaming genomic medicine into routine clinical practice requires actions at each level of the health-care system. Our synthesis emphasized the organizational, social, and cultural implications of reforming practice, highlighting that demonstration of clinical utility and cost-effectiveness, attending to the compatibility of genomic medicine with clinical principles, and involving and engaging patients are key to successful implementation.

Correction: Delivering genomic medicine in the UK National Health Service: a systematic review and narrative synthesis.

In subsection "Genetics/genomics specialists" sentence beginning "Five…" cited reference 32 (Schwarze et al. 2018) and should have been reference 34 (Carroll et al. 2016). While in subsection "The value of genomic medicine" sentence beginning "V…" should have read "'Vassy et al…." Finally, in the same subsection, sentence beginning "Christensen and," should have read "Christensen and Green." The PDF and HTML versions of the Article have been modified accordingly.

Better governance, better access: practising responsible data sharing in the METADAC governance infrastructure.

BACKGROUND: Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and access. Although the open science movement advocates unfettered access to research data, many of the UK's longitudinal cohort studies operate systems of managed data access, in which access is governed by legal and ethical agreements between stewards of research datasets and researchers wishing to make use of them. Amongst other things, these agreements aim to respect the reasonable expectations of the research participants who provided data and samples, as expressed in the consent process. Arguably, responsible data management and governance of data and sample use are foundational to the consent process in longitudinal studies and are an important source of trustworthiness in the eyes of those who contribute data to genomic and biosocial research. METHODS: This paper presents an ethnographic case study exploring the foundational principles of a governance infrastructure for Managing Ethico-social, Technical and Administrative issues in Data ACcess (METADAC), which are operationalised through a committee known as the METADAC Access Committee. METADAC governs access to phenotype, genotype and 'omic' data and samples from five UK longitudinal studies. FINDINGS: Using the example of METADAC, we argue that three key structural features are foundational for practising responsible data sharing: independence and transparency; interdisciplinarity; and participant-centric decision-making. We observe that the international research community is proactively working towards optimising the use of research data, integrating/linking these data with routine data generated by health and social care services and other administrative data services to improve the analysis, interpretation and utility of these data. The governance of these new complex data assemblages will require a range of expertise from across a number of domains and disciplines, including that of study participants. Human-mediated decision-making bodies will be central to ensuring achievable, reasoned and responsible decisions about the use of these data; the METADAC model described in this paper provides an example of how this could be realised.

Patients' Views of Treatment-Focused Genetic Testing (TFGT): Some Lessons for the Mainstreaming of BRCA1 and BRCA2 Testing.

This paper explores patients' views and experiences of undergoing treatment-focused BRCA1 and BRCA2 genetic testing (TFGT), either offered following triaging to clinical genetics (breast cancer) or as part of a mainstreamed care pathway in oncology (ovarian cancer). Drawing on 26 in-depth interviews with patients with breast or ovarian cancer who had undergone TFGT, this retrospective study examines patients' views of genetic testing at this point in their care pathway, focusing on issues, such as initial response to the offer of testing, motivations for undergoing testing, and views on care pathways. Patients were amenable to the incorporation of TFGT at an early stage in their cancer care irrespective of (any) prior anticipation of having a genetic test or family history. While patients were glad to have been offered TFGT as part of their care, some questioned the logic of the test's timing in relation to their cancer treatment. Crucially, patients appeared unable to disentangle the treatment role of TFGT from its preventative function for self and other family members, suggesting that some may undergo TFGT to obtain information for others rather than for self.

Making Sense of SNPs: Women's Understanding and Experiences of Receiving a Personalized Profile of Their Breast Cancer Risks.

Genome wide association studies have identified a number of common genetic variants - single nucleotide polymorphisms (SNPs) - that combine to increase breast cancer risk. SNP profiling may enhance the accuracy of risk assessment and provides a personalized risk estimate. SNP testing for breast cancer risks may supplement other genetic tests in the future, however, before it can be implemented in the clinic we need to know how it will be perceived and received. Semi-structured qualitative interviews were conducted with 39 women who had previously had a breast cancer diagnosis and undergone BRCA1/2 testing, participated in the Variants in Practice (ViP) study and received personalized risk (SNP) profiles. Interviews explored their understanding and experiences of receiving this SNP information. Women reported feeling positive about receiving their personalized risk profile, because it: provided an explanation for their previous diagnosis of cancer, vindicated previous risk management decisions and clarified their own and other family members' risks. A small group was initially shocked to learn of the increased risk of a second primary breast cancer. This study suggests that the provision of personalized risk information about breast cancer generated by SNP profiling is understood and well received. However, a model of genetic counseling that incorporates monogenic and polygenic genetic information will need to be developed prior to clinical implementation.

The Psychosocial Impact of Undergoing Prophylactic Total Gastrectomy (PTG) to Manage the Risk of Hereditary Diffuse Gastric Cancer (HDGC).

Individuals identified as at high risk of developing Hereditary Diffuse Gastric Cancer (HDGC) are advised to undergo prophylactic surgery - have their stomach removed - in their early twenties. Research with (older) cancer patients who undergo gastrectomy for curative reasons suggests that gastric resection has a number of physical and psychosocial sequelae. Because it is difficult to extrapolate the findings of studies of older cancer patients to younger healthy patients who are considering prophylactic total gastrectomy (PTG), the aim of this qualitative interview study was to determine the psychosocial implications of undergoing prophylactic surgery to manage genetic risk. Fourteen men and 13 women from the UK's Familial Gastric Cancer study who had undergone PTG were invited to participate in qualitative interviews. Most reported that undergoing surgery and convalescence was easier than anticipated. There was evidence that age affected experiences of PTG, with younger patients tending to report faster recovery times and more transient aftereffects. All saw the benefits of risk reduction as outweighing the costs of surgery. Surgery was described as having a range of physical impacts (disrupted appetite, weight loss, fatigue, GI symptoms) that had related psychological, social and economic implications. Those considering PTG need to be aware that its impact on quality of life is difficult to predict and negative sequelae may be ongoing for some individuals.

Therapeutic appropriation: a new concept in the ethics of clinical research.

Ethical concerns about therapeutic misconception have been raised since the early 1980s. This concept was originally described as research participants' assumptions that decisions relating to research interventions are made on the basis of their individual therapeutic needs. The term has since been used to refer to a range of 'misunderstandings' that research participants may have. In this paper, we describe a new concept-therapeutic appropriation Therapeutic appropriation occurs when patients, or clinicians, actively reframe research participation as an opportunity to enhance patients' clinical care, while simultaneously acknowledging the generalised research aims. To illustrate the concept of therapeutic appropriation, we draw on data from an interview study which we conducted to investigate the experiences of patients and general practitioners involved in clinical trials in primary care. We argue that therapeutic appropriation has two key elements: comprehension that the research project is not necessarily aiming to benefit participants and the deliberate use of incidental features of the research for personal therapeutic benefit of various kinds. We conclude that therapeutic appropriation is a useful concept that refines understanding of potential ethical problems in clinical research, and points to strategies to address them.

If you build it, they will come: unintended future uses of organised health data collections.

BACKGROUND: Health research increasingly relies on organized collections of health data and biological samples. There are many types of sample and data collections that are used for health research, though these are collected for many purposes, not all of which are health-related. These collections exist under different jurisdictional and regulatory arrangements and include: 1) Population biobanks, cohort studies, and genome databases 2) Clinical and public health data 3) Direct-to-consumer genetic testing 4) Social media 5) Fitness trackers, health apps, and biometric data sensors Ethical, legal, and social challenges of such collections are well recognized, but there has been limited attention to the broader societal implications of the existence of these collections. DISCUSSION: Although health research conducted using these collections is broadly recognized as beneficent, secondary uses of these data and samples may be controversial. We examine both documented and hypothetical scenarios of secondary uses of health data and samples. In particular, we focus on the use of health data for purposes of: Forensic investigations Civil lawsuits Identification of victims of mass casualty events Denial of entry for border security and immigration Making health resource rationing decisions Facilitating human rights abuses in autocratic regimes CONCLUSIONS: Current safeguards relating to the use of health data and samples include research ethics oversight and privacy laws. These safeguards have a strong focus on informed consent and anonymization, which are aimed at the protection of the individual research subject. They are not intended to address broader societal implications of health data and sample collections. As such, existing arrangements are insufficient to protect against subversion of health databases for non-sanctioned secondary uses, or to provide guidance for reasonable but controversial secondary uses. We are concerned that existing debate in the scholarly literature and beyond has not sufficiently recognized the secondary data uses we outline in this paper. Our main purpose, therefore, is to raise awareness of the potential for unforeseen and unintended consequences, in particular negative consequences, of the increased availability and development of health data collections for research, by providing a comprehensive review of documented and hypothetical non-health research uses of such data.

Revealing the results of whole-genome sequencing and whole-exome sequencing in research and clinical investigations: some ethical issues.

The introduction of new sequencing technologies whole-genome sequencing (WGS) and whole-exome sequencing (WES) that are much less finely targeted than previous genetic tests has resulted in ethical debate about what should be done with clinically significant findings that may arise during the sequencing process. In this piece we argue that, in addition to whether the finding has been intentionally sought or arises incidentally, the ethical issues concerning what should be done with WES and WGS findings are also influenced by whether sequencing occurs in a clinical or research setting. We argue that decisions about the disclosure of WGS and WES findings generated in the clinical context are much less ethically contentious than decision making about the feedback of research results. We conclude by calling for greater transparency about the purpose of sample collection, more explicit protocols for transitioning between research and clinical contexts and patients and research participants to be warned of the potential for incidental findings to be generated, their potential significance and the actions that might be taken as a result.

Treating childhood intermittent distance exotropia: a qualitative study of decision making.

BACKGROUND: Engaging patients (parents/families) in treatment decisions is increasingly recognised as important and beneficial. Yet where the evidence base for treatment options is limited, as with intermittent distance exotropia (X(T)), this presents a challenge for families and clinicians. The purpose of this study was to explore how decisions are made in the management and treatment of X(T) and what can be done to support decision-making for clinicians, parents and children. METHODS: This was a qualitative study using face to face interviews with consultant ophthalmologists and orthoptists, and parents of children with X(T). Interview data were analysed using the constant comparative method. RESULTS: The drivers for clinicians in treatment decision-making for X(T) were the proportion of time the strabismus is manifest and parents' views. For parents, decisions were influenced by: fear of bullying and, to a lesser degree, concerns around the impact of the strabismus on their child's vision. Uncertainty around the effectiveness of treatment options caused difficulties for some clinicians when communicating with parents. Parental understanding of the nature of X(T) and rationale for treatment often differed from that of the clinicians, and this affected their involvement in decision-making. Though there were good examples of shared decision-making and parent and child engagement some parents said the process felt rushed and they felt excluded. Parents reported that clinicians provided sufficient information in consultations but they had difficulties in retaining verbal information to convey to other family members. CONCLUSIONS: Overall parents were happy with the care their child received but there is scope for better parent and (where appropriate) child engagement in decision-making. There was an expressed need for written information about X(T) to reinforce what was given verbally in consultations and to share with other family members. Access could be via the hospital website, along with videos or blogs from parents and children who have undergone the various management options. A method of assisting clinicians to explain the treatment options, together with the uncertainties, in a clear and concise way could be of particular benefit to orthoptists who have the most regular contact with parents and children, and are more likely to suggest conservative treatments such as occlusion and minus lenses.