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.

PROJECT NARRATIVE One tragic result of the nation’s opioid epidemic is the increasing number of newborn babies experiencing neonatal opioid withdrawal syndrome (NOWS), up from 7/1,000 in 2004 to 27/1,000 in 2013. NOWS symptoms include poor feeding and vomiting, low weight gain, decreased sleep, and seizures, and studies suggest that in the longer term these children are at risk for cognitive, behavioral, language, attention, and visual problems. RTI proposes to coordinate a trial of pharmaceutical treatment for NOWS in hospitals around the country, providing experienced staff led by a highly qualified principal investigator, and leveraging decades of relevant experience and tailoring existing tools to design the trial, build consensus among the doctors and caregivers, manage the data, protect participant safety, and publish study results.