Congenital disorders requiring major pediatric surgical intervention are infrequent and present complex management problems. Most pediatric surgical studies are methodologically weak, single-center studies, and improved outcomes are likely to require a series of multi-center studies of exemplary quality. The applicant, Dr. Kevin Lally, the A.G. McNeese Professor and Chief of Pediatric Surgery at UT Houston, is a leader in promoting such studies. He has participated in 19 diaphragmatic hernia (CDH). CDH occurs in 1 per 2-4,000 live births; 35% of infants die; survivors are ventilated a mean of 18 days; and 34% have chronic lung disease. K24 funding is requested to substantially increase Dr. Lally's time for 1) Clinical Research including: a) A Multi-center placebo- controlled, randomized trial of antenatal steroids for infants with prenatally diagnosed CDH to improve their oxygenation and reduce time to ventilator independence. Fifteen centers have committed to participate; 7 have IRB approval; and 8, including UT-Houston, have GCRCs. The UT-Houston GCRC provides substantial statistical and database support for this trial. Collaborators at UT Houston include Drs. Larry Gilstrap and Jon Tyson, both experienced in steroid trials, and well-funded investigators in steroid trials, and well-funded investigators in the NICHD Maternal-Fetal and Neonatal Research Networks; and b) Extensive analyses of the CDH registry to define improved predictors of outcome, assess geographic differences and temporal trends, and develop hypotheses and descriptive data needed to design trials to improve outcome. This database has strict quality control, data on 1650 infants and 48 institutions now participate. 2) Mentoring Dr. Lally is a talented mentor; 3 current mentees have recently received a K08 award, a K23 award, and a Young Investigator Award. To enhance his mentoring skills, promote the funding and productivity in his Division of Pediatric Surgery, and augment his methodologic skills in clinical research, Dr. Lally will complete the NIH funded Clinical Research Curriculum work and assist with mentoring teams for young investigators in the Curriculum. He will also conduct systematic reviews of the Cochrane Collaboration and complete the Master's Degree Program in Clinical Research at UT-Houston. K24 funding will help Dr. Lally with his research and mentoring to advance the quality of clinical research in pediatric surgery, develop an expanded international trials network, and improve the outcome of high-risk infants.
