Ethical Legal and Social Issues (ELSI) in Rare Conditions Research and Clinical Practice

患有罕见疾病的个人和家庭可以从基因组技术中大大受益，例如，通过提供诊断（更快）和获得临床试验和新的治疗方法。基因组学的伦理、法律和社会影响（ELSI）需要引起注意，因为例如，这些测试中包含的寿命、预测性、家族性和不确定性信息对于主流专科或要求进行此类测试的患者来说并不总是显而易见的。我们的节点是罕见的ELSI节点，是曼彻斯特，牛津和卡迪夫之间的合作伙伴关系。我们致力于解决重要问题，例如；同意检测和参加临床试验；患有未确诊的罕见疾病；例如，通过儿科或神经病学获得基因组检测；罕见疾病的心理和社会影响；以及设计治疗罕见疾病的临床试验。我们将与患者、家庭、社区、临床医生、学术界和产业界合作，在从转诊途径到罕见病的影响，以及罕见病治疗的临床试验设计等问题上加快研究和推动创新。对于曼彻斯特项目（罕见病临床试验的影响和结果），我们将首先查看目前在罕见病临床试验中使用的结果以及如何测量这些结果。结果是衡量患者参与者的症状以及患者参与者的感觉和功能。接下来，我们将与患者和家属交谈，了解他们的需求、希望和期望是什么，以及他们认为在临床试验的背景下，什么是有意义的改善。然后，我们将与患者团体和其他包括设计和评估临床试验的专家、临床遗传学家、护士、儿科医生、遗传咨询师和工业界讨论我们的发现。本次讨论将集中在需要做些什么来开发方法来衡量与家庭和患者相关的罕见病临床试验的结果。讨论还将提供指导，以制定有效和可靠的衡量结果的方法。对于牛津项目（患有未确诊的罕见疾病的生活），我们将首先分析来自临床伦理、法律和社会研究小组（大约300个访谈）的现有数据，研究人们患有未确诊的罕见疾病的第一手经验。在此基础上，我们将通过与那些经历或参与照顾罕见疾病患者的人的研讨会，确定初步探索的要点。然后，我们将继续研究需要进一步探索的问题，通过对未确诊的罕见疾病患者和家庭的深入访谈，探索没有诊断的生活是什么样的，以及他们如何感觉自己可以得到更好的支持。对于卡迪夫项目（主流化的障碍），我们将与威尔士和英格兰的初级保健和各种专业的从业人员和学员谈论他们在遗传/基因组调查方面的经验。除此之外，我们还将收集有关转介到临床遗传学服务和实验室的详细信息，这些实验室是为了帮助解释遗传/基因组测试的结果，或者表明结果可能在如何报告方面存在困难。我们将安排与从业人员和患者群体进一步接触，讨论他们如何处理我们之前“收集”的去识别的困难情况。我们将(1)开发和分享建议，以最大限度地减少主流专业处理基因组学的问题；(2)明确各专业的培训需求；(3)在与患者代表、皇家学院和英国专业协会进行讨论后，我们将制定良好临床实践和培训未来专家的建议。

Individuals and families living with rare conditions can benefit greatly from genomic technologies by, for example, providing a diagnosis (sooner) and having access to clinical trials and new treatments. The Ethical, Legal and Social Implications (ELSI) of genomics require attention because for example, the longevity, predictive, familial and uncertain information contained within these tests is not always obvious for mainstream specialties or patients requesting such tests. Our Node is the Rare ELSI Node and is a partnership between Manchester, Oxford and Cardiff. We are committed to addressing important issues such as; consent to testing and taking part in clinical trials; living with an undiagnosed rare condition; access to genomic testing through, for example, paediatrics or neurology; the psychological and social impact of rare conditions; and the design of clinical trials for treatment of rare conditions. We will work with patients, families, communities, clinicians, academics and industry to speed up research and drive innovation in issues ranging from referral pathways to the impact of rare conditions, and the design of clinical trials for treatments of rare conditions. For the Manchester project (Impact and outcomes in rare condition clinical trials), we will first look at which outcomes are currently being used in rare condition clinical trials and how these are measured. Outcomes are things like measuring a patient-participant's symptoms and how patient-participants feel and function. Following this we will talk to patients and families to find out what their needs, hopes and expectations are, and what they consider to be meaningful improvement in the context of clinical trials. Then we will discuss what we have found with patient groups and others including experts in designing and assessing clinical trials, clinical geneticists, nurses, paediatricians, genetic counsellors and industry. This discussion will focus on what needs to be done to develop ways to measure the outcomes of rare condition clinical trials that are relevant for families and patients. The discussion will also lead to guidance to develop ways to measure outcomes that are valid and reliable. For the Oxford project (Living with an undiagnosed rare condition) we will begin by analysing existing data from the Clinical Ethics, Law and Society research group (approximately 300 interviews) looking at people's first hand experience of living with an undiagnosed rare condition. From this we will identify points to explore initially through a workshop with those experiencing/involved in the care of those with rare conditions. We will then go on to examine issues that require further exploration through in-depth interviews with people and families with undiagnosed rare conditions to explore what it is like living without a diagnosis and how they feel they could be better supported.For the Cardiff project (Barriers to mainstreaming) we will talk to practitioners and trainees in primary care and a variety of specialities in Wales and England about their experiences of genetic/genome-based investigations. Alongside this we will collect details about the referrals to clinical genetics services and to laboratories that are made to help with interpreting the results of genetic/ genomic tests or that suggest there may be a difficulty with how the results might be reported. We will arrange further contact with the practitioners and the patient groups to discuss how they would manage the de-identified difficult scenarios that we had previously 'collected'.We will (1) develop and share suggestions to minimise the problems from handling genomics in mainstream specialties; (2) identify training needs of various specialties; (3) following discussions with patient representatives, Royal Colleges and UK specialty societies, we will develop proposals for good clinical practice and for the training of future specialists.