Data Coordinating Center (DCC) for the Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial (NOWS PhaCET)

项目总结/摘要 在优化新生儿阿片类戒断综合征的药理学治疗方面存在主要知识差距 （NOWS），一个紧迫的公共卫生问题。迫切需要严格、高质量的随机试验， 发展这一领域新生儿医学的证据基础和最佳做法。作为回应，NICHD Heal Initiative NOWS药物治疗比较有效性试验（NOWS PhaCET） 联合体将设计并实施一项多中心、比较有效性、随机对照试验 (RCT)评估告知临床实践指南的NOWS的最佳药理学治疗。 迫切需要一个独立且经验丰富的数据协调中心（DCC）， 高质量和公正的生物统计专业知识，以解决重大的方法学挑战， 通过（1）建立共识以帮助识别关键的方法学问题;（2）设计和实施此类试验 把客观的统计专业知识的概念，设计和分析，一个严格可行的 随机试验（有适当的监测）;（3）制定程序和系统，以增加 联合体的效率，确保试验可行性，有效利用有限的试验参与者， （4）确保研究设计、开发、数据收集、数据质量和数据的标准化 现有HEAL活动的分析;（5）研究结果、公开报告和公众使用的传播 数据作为NICHD新生儿研究网络（NRN）的长期DCC和正在进行的 在新生儿阿片类药物戒断临床试验（ACT NOW）研究中，RTI成功地与 设计和实施30多项新生儿RCT，为临床实践提供信息。我们的具体目标是 NOWS PhaCET的DCC将（1）通过合作建立 一致同意制定一项统一的议定书，以解决以下问题的独特可行性和实施挑战： NOWS中的药理学RCT;（2）通过灵活、高效和高质量的数据优化生产力， 研究管理，促进HEAL数据的协调和共享;（3）保护参与者的安全， 研究完整性与独立数据安全和监查委员会（DSMC）、单一IRB合作 （sIRB）、NICHD和FDA（根据需要）;（4）提供及时的报告和数据分析，并与 调查人员对所有联合体的分析和出版物;（5）提供必要的后勤， 合同、通信和监管支持。该应用程序的独特优势包括（1） 高素质的PI和工作人员在新生儿和NOWS试验的各个方面都有独特的经验，包括 神经发育随访;（2）在围产期合作和科学生产力方面的良好记录 研究;（3）最先进的基础设施，包括为新生儿/婴儿定制的灵活工具、流程和系统。 纳入随访的NOWS RCT;（4）根据需要提供的多学科专家;（5）深度和 广泛的专家工作人员，具有灵活的行政结构，能够迅速应对不断变化的需求。

PROJECT SUMMARY/ABSTRACT Major knowledge gaps exist in optimizing pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS), a pressing public health issue. Rigorous, high quality, randomized trials are urgently needed to develop the evidence base and best practices for neonatal medicine in this area. In response, the NICHD Heal Initiative NOWS Pharmacological Treatments Comparative Effectiveness Trial (NOWS PhaCET) consortium will design and implement a multi-center, comparative effectiveness, randomized controlled trial (RCT) to assess the optimal pharmacological treatment for NOWS that informs clinical practice guidelines. There is a crucial need for an independent and experienced Data Coordinating Center (DCC) to provide high-quality and impartial biostatistical expertise to address the substantial methodologic challenges in the design and conduct of such a trial by (1) building consensus to help identify critical methodologic issues; (2) bringing objective statistical expertise to the conception, design, and analyses of a rigorous and feasible randomized trial (with appropriate monitoring); (3) developing processes and systems to increase the efficiency of the consortium, ensure trial feasibility, and effective use of limited trial participants and resources; (4) ensuring standardization of study design, development, data collection, data quality, and data analyses with existing HEAL activities; and (5) dissemination of study results, public reports, and public use data. As longtime DCC for the NICHD Neonatal Research Network (NRN) and the ongoing Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) studies, RTI has successfully collaborated in the design and implementation of 30+ RCTs in neonates informing clinical practice. Our Specific Aims as the DCC for NOWS PhaCET are to (1) Enhance the scientific rigor of the consortium by collaboratively building consensus for a uniform protocol that addresses the unique feasibility and implementation challenges of pharmacological RCTs in NOWS; (2) Optimize productivity with flexible, efficient, and high quality data and study management, and promote HEAL data harmonization and sharing; (3) Protect participant safety and study integrity working with the independent Data Safety and Monitoring Committee (DSMC), single IRB (sIRB), NICHD, and FDA (as needed); (4) Provide timely reporting and data analysis, and collaborate with investigators on all consortium analyses and publications; and (5) Provide the necessary logistical, contractual, communications, and regulatory support. The unique strengths of this application include (1) a highly qualified PI and staff uniquely experienced in all aspects of both neonatal and NOWS trials including neurodevelopmental follow-up; (2) proven track record of collaboration and scientific productivity in perinatal studies; (3) state-of-the-art infrastructure of flexible tools, processes, and systems customized for neonatal/ NOWS RCTs incorporating follow-up; (4) multidisciplinary experts available as needed; and (5) depth and breadth of expert staff with an agile administrative structure that can respond quickly to changing needs.