Mentorship of Early-Career Clinicians in Bronchopulmonary Dysplasia Drug Therapies

患有支气管肺发育不良（BPD）的早产儿经常死亡，幸存者终身患病。 BPD是最常见的早产儿发病率，每年影响超过18，000名婴儿。NIH将BPD定义为 在36周龄时接受外源性氧气或气道正压通气。BPD的成本是 在社会和经济方面，儿童健康和生活质量受损、家庭压力和 经济困难，医疗费用增加。BPD的后果是灾难性的 神经科医生经常使用未经证实有效的药物来预防和治疗BPD。 不幸的是，没有FDA批准的药物用于预防或治疗BPD。开发安全和 有效的BPD药物是改善公共健康的理想机会，并提供了一个平台， 学员在试验设计、法规要求和严格的定量方法方面的专业知识， 应用于自己的独立研究生涯。 研究人员Matthew M. Laughon，医学博士，公共卫生硕士是一位执业的微生物学家， 流行病学和临床药理学培训。Laughon博士已经获得了培训生发展的机会 北卡罗来纳州查佩尔山的大学项目，包括新生儿-围产期部 医学，Gillings公共卫生学院和Eshelman药学院。Laughon博士也有一个 与世界上最大的学术研究机构杜克临床医学中心（Duke Clinical）建立了长期的学术合作关系 研究院通过这些项目，Laughon博士将指导在斯坦福大学和杜克大学的学员，并提供一个 学员获得流行病学、临床药理学或 药物流行病学开始临床研究者将遵循逻辑进展，包括设计 一个原始的假设驱动的研究项目，完成教学研究，参与一对一， 小组指导，定期评估和反馈。受训人员将侧重于筹备和举办 新生儿肺部疾病的早期药物试验，主要是BPD。这些期望的可行性证明是 由现任和前任学员提供，他们在定量，面向患者的研究中取得了成功。 确定早产儿BPD药物的PK和安全性是一项迫切的、未得到满足的公共卫生需求。 研究BPD的药物是一个理想的机会，可以解决研究空白的问题， 在早产儿中使用药物是因为：1）患有BPD的早产儿有终身的发病率; 2）没有 已被证明可以预防或治疗BPD的药物; 3）新生儿医生通常使用药物治疗BPD。 未进行适当剂量和安全性研究的早产儿;以及4）预防死亡和发病 与早产相关的疾病有终生的益处。拟议的受训人员领导的研究项目将使用一个 10种常用药物的机会主义研究设计，为学员提供一个平台， 临床研究技能和早产儿药物开发的合理方法方面。

Premature infants with bronchopulmonary dysplasia (BPD) often die and survivors have life-long morbidities. BPD is the most common morbidity of prematurity, affecting >18,000 infants per year. The NIH defines BPD as the receipt of exogenous oxygen or positive airway pressure at 36 weeks adjusted age. The costs of BPD are both social and economic and are measured in impaired childhood health and quality of life, family stress and economic hardship, and increased healthcare costs. Because the consequences of BPD are catastrophic, neonatologists frequently use drugs without proven efficacy in an attempt to prevent and treat BPD. Unfortunately, there are no FDA approved drugs for the prevention or treatment of BPD. Developing safe and effective drugs for BPD is an ideal opportunity to improve public health and provides a platform to develop trainees’ expertise in trial design, regulatory requirements, and rigorous quantitative methods that will be applied to their own independent research career. The investigator, Dr. Matthew M. Laughon, MD, MPH is a practicing neonatologist with an MPH in epidemiology and training in clinical pharmacology. Dr. Laughon has secured access for trainee development to The University of North Carolina at Chapel Hill programs including the Division of Neonatal-Perinatal Medicine, the Gillings School of Public Health, and the Eshelman School of Pharmacy. Dr. Laughon also has a longstanding academic partnership with the world’s largest academic research organization, the Duke Clinical Research Institute. Through these programs, Dr. Laughon will mentor trainees at UNC and Duke and provide a pathway for trainees to secure advanced training in epidemiology, clinical pharmacology, or pharmacoepidemiology. Beginning clinician investigators will follow a logical progression including designing an original hypothesis driven research project, completing didactic studies, participation in one on one and group mentoring, and regular evaluation and feedback. Trainees will focus on the preparation and conduct of early-phase drug trials in neonatal lung disease, primarily BPD. Proof of the feasibility of these expectations is provided by current and former trainees who have achieved success in quantitative, patient-oriented research. Determining the PK and safety of drugs for BPD in premature infants is an urgent, unmet public health need. Investigating drugs for BPD represents an ideal opportunity to approach the problem of the research gap of drugs in premature infants because: 1) Premature infants with BPD have life-long morbidities; 2) There are no drugs that have been proven to prevent or treat BPD; 3) Neonatologists are commonly using drugs in premature infants without appropriate dosing and safety studies; and 4) Preventing mortality and morbidities associated with premature birth has life-long benefits. The proposed trainee-led research project will use an opportunistic study design of 10 commonly used drugs that will provide a platform for trainee to develop all aspects of clinical research skills and a rational approach to drug development in premature infants.