Early Check: A Collaborative Innovation to Facilitate Pre-Symptomatic Clinical Trials in Newborns

项目摘要/摘要 新生儿筛查(NBS)旨在对符合以下条件的严重情况进行症状前识别 是必须及早开始的有效治疗方法。国家统计局政策的核心是有证据表明有症状前期 治疗比症状出现后的治疗更有效。不幸的是，这样的证据很难 聚集，因为大多数提名的情况很少见，并且需要努力确定症状前期 用于临床试验的婴儿数量很大。研究人员和倡导者发现自己陷入了经典的“第二十二条军规” 情况-NBS在没有足够证据的情况下不能发生，但收集这些证据必然需要 大规模人群筛查。这个问题是翻译研究的一个巨大障碍，以至于 许多障碍将永远没有必要的证据来证明纳入国家统计局的计划是合理的。 我们建议开发和实施早期检查-一项研究计划，在该计划中，自愿筛查 条件小组是在全州范围内提供的。及早检查将允许快速筛查新的 候选条件，促进对早期疾病的了解，并促进登记和临床试验 招聘。我们将建立和实施一项实验性研究计划，并进行持续评估 在我们从实施经验中学习的过程中，我们对程序进行修改和改进的组件 以及与直接受筛查影响的普通公众和家庭的接触。 一旦我们最终确定了该计划的所有方面，我们将为逐步扩大的一组 每年向北卡罗来纳州所有12万个分娩家庭提供卫生条件。我们的第一个条件是提供筛查 将是脊髓性肌萎缩症，一种危及生命的退行性运动神经元疾病。我们将决定 参与率；进行筛查；返回结果；提供咨询和临床服务；支持 家庭参与照料决策；通知家庭正在进行的临床试验；为家庭提供支持 决定他们是否想要参加临床试验；并跟踪儿童和家庭一段时间的研究 筛查的益处、危害和心理社会结果。我们将尽早寻求外部资金进行扩张 检查其他候选障碍，如脆性X综合征。实施数据将用于细化 该过程，通知复制，并建立用于测试其他候选条件的基础设施。至 为了实现长期生存，我们将发展基于合作的公私伙伴关系模式 与联邦机构、基金会、患者权益倡导团体和行业接触。

PROJECT SUMMARY/ABSTRACT Newborn screening (NBS) is designed for pre-symptomatic identification of serious conditions for which there are effective treatments that must begin early. Central to NBS policy is evidence that pre-symptomatic treatment is more effective than treatment after symptoms appear. Unfortunately, such evidence is difficult to amass because most nominated conditions are rare and the effort required to identify pre-symptomatic infants for clinical trials is substantial. Researchers and advocates find themselves in a classic “Catch 22” situation—NBS cannot happen without sufficient evidence, but gathering this evidence necessarily requires large-scale population screening. This problem is such a formidable barrier to translational research that many disorders will never have the evidence needed to justify inclusion in NBS programs. We propose to develop and implement Early Check—a research program in which voluntary screening for a panel of conditions is offered on a statewide basis. Early Check would allow rapid screening for new candidate conditions, advance understanding of early disease, and facilitate registry and clinical trial recruitment. We will build and implement an experimental research program with an ongoing evaluation component in which we revise and improve the program as we learn from our implementation experiences and engagement with the general public and families directly affected by screening. Once we have finalized all aspects of the program, we will offer screening for a gradually expanding set of conditions to all 120,000 birthing families per year in North Carolina. Our first condition offered for screening will be spinal muscular atrophy, a life-threatening degenerative motor neuron disorder. We will determine participation rates; conduct screening; return results; provide counseling and clinical services; support families in caregiving decisions; inform families of ongoing clinical trials; provide support for families in deciding whether they want to participate in a clinical trial; and follow children and families over time to study benefits, harms, and psychosocial outcomes of screening. We will seek external funds to expand Early Check to other candidate disorders, such as fragile X syndrome. Implementation data will be used to refine the process, inform replication, and establish an infrastructure for testing other candidate conditions. To achieve long-term viability, we will develop a model of public-private partnerships based on collaborative engagement with federal agencies, foundations, patient advocacy groups, and industry.