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

基本信息

批准号：
8675893
负责人：
Melissa Pittel Wasserstein
金额：
$ 57.24万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
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/8675893
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

项目摘要

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. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE We will conduct a pilot newborn screening for Fabry, Gaucher, Niemann-Pick Types A and B, and Pompe diseases in approximately 80,000 infants born in high birth rate, ethnically diverse New York City hospitals in order to validate the screening assay and to define the natural history of these disorders. Prospective clinical, laboratory, and radiographic data will be collected and analyzed in order to develop evidence-based algorithms for the diagnosis and treatment of these rare disorders. In addition, the unique ethical, legal, an psychosocial issues that are associated with screening for these disorders will be explored.

描述（由申请人提供）：项目摘要包括纽约在内的多个州已提议对新生儿法布里病、戈谢病、尼曼皮克病 A 型和 B 型以及庞贝病进行筛查。这些溶酶体贮积病 (LSD) 中的每一种都具有广泛的表型谱，从严重的婴儿发病的疾病到成人发病的较温和的表型。因此，针对这些疾病的新生儿筛查提出了一系列独特的复杂问题，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测定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，以及开发算法以协助临床决策是否以及何时开始治疗。此外，检测婴儿潜在的迟发性疾病还存在新的伦理、法律和社会问题。该提案将通过与纽约州新生儿筛查计划结合实施试点新生儿筛查来探讨这些问题，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疾病发病率。筛查数据将与新生儿筛查转化研究网络 (NBSTRN) 共享。西奈山医疗中心的 LSD 专家将跟踪所有被识别的婴儿，进行诊断评估、监测和治疗。这项研究和现有特定疾病临床数据库生成的自然历史数据也将与 NBSTRN 共享，目标是开发模型来预测整个生命周期中疾病的发病年龄，以优化治疗并避免过早使用昂贵的药物。疗法。还将探讨 LSD 筛查的心理方面，重点关注晚发性疾病筛查是否会产生有害的短期或长期影响。将通过问卷和访谈来评估心理影响，以评估婴儿有患婴儿期疾病与晚发性疾病风险的父母的反应。我们还将通过分析监测和治疗成本以及潜在的保险困难来分析阳性诊断对家庭的经济影响。根据这些结果，将召开伦理小组会议，讨论与这些疾病检测相关的特殊问题，包括潜在危害，然后我们将使用这些信息作为制定新生儿 LSD 筛查政策建议的基础。一般疾病，特别是晚发疾病。此外，还将举行一次研讨会，讨论参与成人发病疾病新生儿筛查的医疗团队的法医学责任范围和期限。总之，这些研究应该导致基于证据的、伦理敏感的新生儿筛查和长期随访政策的制定，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。公共卫生相关性：项目叙述我们将对纽约市高出生率、种族多元化的医院中出生的约 80,000 名婴儿进行法布里病、戈谢病、尼曼匹克 A 型和 B 型以及庞贝氏病的试点新生儿筛查，以验证筛查分析并定义这些疾病的自然史。将收集和分析前瞻性临床、实验室和放射学数据，以便开发用于诊断和治疗这些罕见疾病的循证算法。此外，还将探讨与这些疾病筛查相关的独特的伦理、法律和社会心理问题。