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受益很大，例如，通过提供诊断(更快)并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)需要关注，因为例如，这些测试中包含的寿命、预测性、家族性和不确定信息对于主流专科或要求进行此类测试的患者并不总是明显的。我们的节点是罕见的ELSI节点，是曼彻斯特、牛津和卡迪夫的合作伙伴。我们致力于解决以下重要问题：同意测试和参加临床试验；与未确诊的罕见疾病生活在一起；通过儿科或神经科等途径获得基因组测试；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、学者和业界合作，在从转诊路径到罕见疾病的影响，以及罕见疾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)，我们将首先看看目前在罕见病临床试验中使用了哪些结果，以及如何衡量这些结果。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。随后，我们将与患者和家属交谈，了解他们的需求、希望和期望，以及他们认为在临床试验中有哪些有意义的改善。然后，我们将与患者团体和其他人讨论我们的发现，其中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、遗传顾问和行业。这一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情况临床试验的结果。讨论还将产生指导，以制定衡量有效和可靠结果的方法。对于牛津大学的项目(患有未诊断的罕见疾病)，我们将从分析临床伦理、法律和社会研究小组(约300次采访)的现有数据开始，寻找人们生活在未诊断的罕见疾病中的第一手经验。为此，我们将通过与那些经历/参与护理罕见疾病的人举行研讨会，初步确定要探索的要点。然后，我们将通过对患有未确诊罕见疾病的人和家庭的深入采访来研究需要进一步探索的问题，以探索没有诊断的生活是什么感觉，以及他们如何感觉自己可以得到更好的支持。对于加的夫项目(主流化的障碍)，我们将与威尔士和英格兰初级保健和各种专业的从业者和实习生谈论他们在遗传/基因组研究方面的经验。此外，我们将收集有关转诊到临床遗传学服务机构和实验室的详细信息，这些实验室是为了帮助解释基因/基因组测试的结果，或者表明如何报告结果可能存在困难。我们将安排与从业者和患者团体进一步联系，讨论他们将如何管理我们先前收集的未确定的困难情况。我们将(1)开发和分享建议，以最大限度地减少在主流专科处理基因组学所带来的问题；(2)确定各种专科的培训需求；(3)在与患者代表、皇家学院和英国专科学会讨论后，我们将为良好的临床实践和未来专家的培训制定建议。

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.