LSDs:A Pilot NBS and Examination of the Associated Ethical Legal & Social Issues

LSD:试点国家统计局和相关道德法律审查

• 批准号: 8537501
• 负责人: Melissa Pittel Wasserstein
• 金额: $ 56.24万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8537501
• 关键词: Adopted; Adult; Age of Onset; Algorithms; Anxiety; Biochemical; Biological Assay; Birth Rate; Blood; Clinical; Complex; Data; Databases; Development; Diagnosis; Diagnostic; Disease; Educational workshop; Ethical Issues; Ethics; Evaluation; Fabry Disease; Familiarity; Family; Gaucher Disease; Globoid cell leukodystrophy; Glycogen storage disease type II; Goals; Hematopoietic Stem Cell Transplantation; Heterogeneity; Incidence; Infant; Informatics; Interview; Investigation; Laboratories; Late-Onset Disorder; Legal; Length; Long-Term Effects; Longevity; Longitudinal Studies; Lysosomal Storage Diseases; Medical; Medical Ethics; Medical center; Mental Depression; Metabolic Diseases; Methods; Modeling; Monitor; Mutation; Natural History; Neonatal Screening; New York; New York City; Newborn Infant; Niemann-Pick Diseases; Onset of illness; Parents; Patients; Performance; Phenotype; Policies; Population Heterogeneity; Psychological Impact; Psychosocial Influences; Publishing; Questionnaires; Rare Diseases; Reaction; Recommendation; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Risk; Safety; Signs and Symptoms; Spottings; Stress; Structure; Sum; Testing; Translational Research; Treatment Cost; Treatment Efficacy; Urban Hospitals; base; biobank; clinical decision-making; diagnostic accuracy; disease natural history; economic impact; ethical legal social implication; evidence base; experience; follow-up; infancy; interest; international center; late disease onset; novel; premature; programs; prospective; psychologic; public health relevance; screening; socioeconomics; symposium; treatment center

DESCRIPTION (provided by applicant): PROJECT SUMMARY Newborn screening for Fabry, Gaucher, Niemann Pick Types A and B, and Pompe diseases has been proposed in several states, including New York. Each of these lysosomal storage diseases (LSD) has a broad phenotypic spectrum ranging from severe infantile-onset disease to adult-onset, milder phenotypes. Thus, newborn screening for these disorders presents a unique set of complex issues that require investigation prior to the initiatio of mass newborn screening. These issues include determining the clinical and diagnostic accuracy of the screening assay, investigating how to correctly predict phenotype in asymptomatic newborns, and developing algorithms to assist with clinical decision-making about if and when to initiate therapy. In addition, there are novel ethical, legal, and social issus associated with testing infants for potentially later-onset disorders. This proposal will explore these issues by implementing a pilot newborn screen in conjunction with the New York State Newborn Screening Program to evaluate the analytic and clinical validity of the screening test and to determine disease incidence in an ethnically diverse population. Screening data will be shared with the Newborn Screening Translational Research Network (NBSTRN). All identified infants will be followed by LSD experts at The Mount Sinai Medical Center for diagnostic evaluation, monitoring, and treatment. Natural history data generated from this research and from existing disease-specific clinical databases will also be shared with the NBSTRN, with the goal of developing models to predict age of onset of disease over the lifespan in order to optimize treatment and avoid premature use of costly therapies. The psychological aspects of screening for the LSDs will also be explored, focusing on whether screening for later-onset disorders has harmful short or longer term effects. The psychological impact will be assessed using questionnaires and interviews to evaluate the reactions of parents whose infants are at risk to develop infantile versus later-onset disease. We will also initiate an analysis of the economic impact of a positive diagnosis on families by analyzing monitoring and treatment costs as well as potential difficulties with insurability. Based on these results, an ethics panel will b convened to discuss the particular concerns, including potential harms, that are associated with testing for these disorders, and we will then use this information as the basis for formulating policy recommendations on newborn screening for LSDs in general, and later onset diseases in particular. In addition, a symposium will be held to discuss the extent and length of medicolegal responsibility of the medical team involved in the newborn screening of a patient with adult onset disease. In sum, these studies should result in the development of evidence-based, ethically-sensitive, newborn screening and long-term follow up policies that will have considerable influence as newborn screening for the LSDs becomes widely adopted.

描述(由申请人提供)： 项目概述包括纽约州在内的几个州已经提议对Fabry、Gaucher、Niemann Pick A型和B型以及庞培病进行新生儿筛查。这些溶酶体储存疾病(LSD)中的每一种都有广泛的表型谱，从严重的婴儿起病到成人起病、较轻的表型。因此，对这些疾病的新生儿筛查提出了一套独特的复杂问题，需要在开始大规模新生儿筛查之前进行调查。这些问题包括确定筛查分析的临床和诊断准确性，研究如何正确预测无症状新生儿的表型，以及开发算法以帮助临床决策是否以及何时开始治疗。此外，还有一些新的伦理、法律和社会问题与检测婴儿潜在的迟发性疾病有关。这项提案将通过与纽约州新生儿筛查计划一起实施新生儿筛查试点来探讨这些问题，以评估筛查测试的分析和临床有效性，并确定不同种族人群中的发病率。筛查数据将与新生儿筛查翻译研究网络(NBSTRN)共享。所有确认的婴儿将由西奈山医学中心的LSD专家进行跟踪，以进行诊断评估、监测和治疗。这项研究和现有疾病特定临床数据库产生的自然病史数据也将与NBSTRN共享，目的是开发预测一生中疾病发病年龄的模型，以便优化治疗并避免过早使用昂贵的治疗方法。还将探讨筛查LSD的心理学方面，重点是筛查晚发型障碍是否具有有害的短期或长期影响。将使用问卷和访谈来评估心理影响，以评估婴儿有患婴儿与晚发疾病风险的父母的反应。我们还将通过分析监测和治疗费用以及保险方面的潜在困难，启动对阳性诊断对家庭的经济影响的分析。根据这些结果，我们将召开一个伦理小组，讨论与检测这些疾病相关的特殊关切，包括潜在的危害，然后我们将利用这些信息作为制定一般新生儿LSD筛查，特别是晚发型疾病的政策建议的基础。此外，还将举行一次研讨会，讨论参与新生儿筛查成人疾病患者的医疗队的法医责任范围和期限。总而言之，这些研究应该导致制定循证、伦理敏感的新生儿筛查和长期后续政策，随着LSD新生儿筛查的广泛采用，这些政策将产生相当大的影响。