Bench to Bassinet Program

Eileen King, PhD, associate professor, in the Division of Biostatistics and Epidemiology, along with, Peter White, PhD, professor and director of the Division of Biomedical Informatics (BMI), received a $32.5 million, five-year grant to serve as the Administrative Coordinating Center, and data hub for the National Institutes of Health’s (NIH) Bench to Bassinet Program (B2B). B2B is a national, multi-site, collaborative program designed to accelerate research into the molecular basis of congenital heart disease, from discovery and translational research to clinical testing.

The purpose of this federally funded program is to coordinate activities for the Cardiovascular Development Consortium and the Pediatric Cardiac Genomics Consortium, two leading scientific consortia dedicated to the discovery and modeling of genomic data for thousands of individuals with congenital and/or acquired heart disease and their influence on clinical outcomes. Division of Biostatistics and Epidemiology faculty and staff contribute to the conduct and administrative oversight of the project, including the design and development of databases capturing clinical and phenotypic data, statistical modeling and analysis of project data, and the management and tracking of biological specimens. We work in close collaboration with the Division of Biomedical Informatics in the design and development of a genomic data hub involving more than 150 terabytes of molecular and clinical cardiac data.

The B2B program is an important component of the Division of Biostatistics and Epidemiology and its collaborative ties with other divisions, highlighting many of the inherent strengths of the Division in the core areas of biostatistics, epidemiology, and data management. The B2B program offers the medical center a lead role in determining new directions for pediatric heart research leading to greater understanding of how patients’ genetic profiles is something clinicians can use to better predict the course of illness, target interventions, and result in novel cures for many of today’s most challenging cardiovascular conditions. B2B is believed to be the largest single award ever received by Cincinnati Children’s.

Methods Development

In FY 2016, faculty and staff from the division led independent research in many areas of methods development, nearly all with specific applications to pediatric science and medicine. Examples of such methodologies included new applications for analyzing zero-inflated repeated count data (see significant publication by Gupta), semiparametric mixed methods for nested repeated measures data (see significant publication by Szczesniak), as well as propensity score matching techniques with time-varying exposures. Other methods with direct applications to pediatrics included semiparametric regression modeling of multivariate panel count data with informative observation times, statistical analysis of metabolomics data, and novel methods for accelerated failure time models with incomplete predictors. Professional journals in which our methodological work appeared in FY 2016 include Communication of Statistics, Journal of Multivariate Analysis, Lifetime Data Analysis, Annals of Epidemiology, Metabolomics, and the Journal of Modern Applied Statistical Methods. This work is funded through both intramural and extramural awards. Two faculty members, in particular, Dr. Bin Huang, PhD, and Dr. Mi-Ok Kim, were recipients of PCORI Methods Awards designed specifically to foster the development of new approaches for advancing patient centered research. The Division formed shared interest groups in causal inference and adaptive clinical trials to promote additional work in these two important areas of pediatric research.

Population-based Research

The Division of Biostatistics and Epidemiology is the research hub for a variety of population-based cohorts aimed at understanding and improving child health in the context of where children and families live—in the community. These epidemiologic studies and collaborations allow our researchers to understand normal growth and development, the long-term impact of the environment or childhood lifestyle on health and disease, and intergenerational influences on child health.

There are four large Cincinnati-based cohorts directed from within the Division, led by Drs. Patrick Ryan, PhD, MS; Jane Khoury, PhD; Jessica Woo, MHSA, PhD; and Alonzo Folger. Three of these cohorts represent traditional longitudinal epidemiologic cohorts, aimed at understanding the long-term role of early life exposures (e.g., in utero exposure to glucose or childhood exposure to air pollution or allergens) or measured risk factors (e.g., blood lipids, blood pressure, body mass index) on adolescent or adult outcomes, such as cardiovascular, renal, metabolic, allergy, asthma and neurodevelopment outcomes. These studies include the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS, PI: Dr. Patrick Ryan; see significant publications section by Brokamp), the Diabetes in Pregnancy study (PI: Dr. Jane Khoury), and the Princeton Lipid Research Study (PI: Dr. Jessica Woo), each of which has enrolled between 700 and 2,500 children and families. Some of these families have been followed and studied for 40 years. The fourth cohort is the research arm of a large regional parenting support home-visiting program, Every Child Succeeds (Lead Epidemiologist: Dr. Alonzo Folger; see featured publication), with robust databases designed to study such outcomes as pediatric injury, maternal depression, pediatric primary care, and the effects of maternal adversity on child development and the mediational role of epigenetics.

In addition to these large cohorts, the Division is involved in a number of other initiatives to study and improve the health of Cincinnatians. In an ongoing collaboration with Hamilton County Public Health, Dr. Folger has provided epidemiologic and statistical expertise to support investigation and surveillance of the local syphilis epidemic. Dr. Richard Ittenbach, PhD, collaborated with the Biodynamic Center at Cincinnati Children's to refine a county-wide screening of female athletes in Boone County, KY, to understand biomechanical profiles predisposing athletes to ACL injury. These and similar collaborations from our Division extends Cincinnati Children’s research and impact beyond the clinical setting and situations that arise during clinical care, to truly understand and influence health in the communities we serve.

Team Science

The Division of Biostatistics and Epidemiology values tremendously its collaborative work with investigators throughout the medical center. In FY 2016, Division of Biostatistics and Epidemiology faculty and staff collaborated with investigators on funded studies from 34 of the 59 clinical and research divisions within the hospital, fully embracing the team science model. Divisional faculty and staff participated in 133 active research grants and contracts, with annual direct costs totaling $152M (divisional direct costs: $22M). Specific examples of successful team collaborations in which DBE faculty and staff participated in FY2016 were the Center for Clinical and Translational Science and Training in which 8 faculty and staff serve in active leadership positions, including statistical analysis and study design, clinical research ethics, and clinical data management. Learning Networks represent another important area of collaborative involvement. In conjunction with the Anderson Center and a number of other clinical divisions, DBE members are helping reshape the way in which clinical data are used to inform and improve clinical care system-wide.