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匪浅，例如，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、法律的和社会影响（ELSI）需要关注，因为例如，这些测试中包含的寿命、预测性、家族性和不确定性信息对于主流专业或要求此类测试的患者来说并不总是明显的。我们的节点是罕见的ELSI节点，是曼彻斯特，牛津和卡迪夫之间的合作伙伴关系。我们致力于解决重要问题，如：同意测试和参加临床试验;与未确诊的罕见疾病一起生活;通过儿科或神经科等途径进行基因组测试;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，学者和行业合作，加快研究并推动从转诊途径到罕见疾病影响以及罕见疾病治疗临床试验设计等问题的创新。 对于曼彻斯特项目（罕见病临床试验的影响和结果），我们将首先研究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。结果是测量患者参与者的症状以及患者参与者的感觉和功能。在此之后，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中有意义的改善。然后，我们将与患者团体和其他人讨论我们的发现，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，遗传咨询师和行业。本次讨论将集中在需要做些什么来制定方法来衡量与家庭和患者相关的罕见疾病临床试验的结果。讨论还将为制定衡量有效和可靠成果的方法提供指导。对于牛津项目（与未确诊的罕见疾病一起生活），我们将开始分析来自临床伦理学，法律和社会研究小组的现有数据（约300次采访），研究人们与未确诊的罕见疾病一起生活的第一手经验。从这一点上，我们将确定点，通过与那些经历/参与照顾那些罕见的条件研讨会初步探索。然后，我们将继续研究需要进一步探索的问题，通过对患有未确诊罕见疾病的人和家庭进行深入采访，探索没有诊断的生活是什么样子，以及他们如何感觉他们可以更好地康复。（纳入主流的障碍）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受训人员谈论他们在遗传/基因组方面的经验，基于调查。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，这些转介是为了帮助解释遗传/基因组检测的结果，或者表明如何报告结果可能存在困难。我们会安排与医生及病人团体进一步接触，讨论他们如何处理我们先前“收集”的“去识别化”困难情况。我们会（1）发展及分享建议，以尽量减少主流专科在处理基因组学时出现的问题;（2）确定各专科的培训需求;（3）研究如何处理基因组学的问题。（3）在与病人代表、皇家学院和英国专科学会讨论后，我们将制定良好临床实践和培训未来专科医生的建议。

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.