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）： 在包括纽约在内的几个州提出了针对Fabry，Gaucher，Niemann Pick A类型A和B类型的新生儿筛查，以及庞贝疾病。这些溶酶体储存疾病（LSD）中的每一个都有广泛的表型光谱，从严重的婴儿发作疾病到成人发作，温和的表型。因此，这些疾病的新生儿筛查提出了一组独特的复杂问题，这些问题需要在大规模新生儿筛查开始之前进行调查。这些问题包括确定筛查测定法的临床和诊断准确性，研究如何正确预测无症状新生儿中的表型，以及开发算法以协助有关是否以及何时开始治疗的临床决策。此外，与对潜在的后来发作疾病进行测试有关的新颖的道德，法律和社会问题。该建议将通过与纽约州新生儿筛查计划结合实施新生儿筛查，以评估筛查测试的分析和临床有效性，并确定种族多样性多样化的疾病发生率，从而探索这些问题。筛选数据将与新生儿筛选翻译研究网络（NBSTRN）共享。所有确定的婴儿将在西奈山医学中心的LSD专家之后进行诊断，监测和治疗。这项研究和现有疾病特异性临床数据库产生的自然历史数据也将与NBSTRN共享，其目的是开发模型以预测寿命中疾病的发作年龄，以优化治疗并避免过早使用昂贵的治疗疗法。还将探讨LSD筛查的心理方面，重点是筛查后来发作的疾病是否具有有害的短期或长期影响。心理影响将使用问卷调查和访谈评估，以评估婴儿有可能发育婴儿与后来发作疾病的父母的反应。我们还将通过分析监测和治疗成本以及可保险性的潜在困难来开始分析积极诊断对家庭的经济影响。基于这些结果，伦理小组将召集B召集与这些疾病测试有关的特定问题，包括潜在危害，然后我们将使用此信息作为制定有关LSDS新生儿筛查的政策建议的基础。一般，后来发作疾病。此外，还将举行研讨会，讨论参与新生儿筛查成人疾病的新生儿筛查的医疗团队的责任的程度和时间。总而言之，这些研究应导致发展基于证据的，道德敏感的，新生儿筛查和长期随访政策，随着LSD的新生儿筛查将被广泛采用。