Cancer and Blood Diseases Institute (CBDI) Collaborations
The Data Management and Analysis Center (DMAC) celebrates its first collaboration with the Cancer and Blood Diseases Institute (CBDI) and drug sponsor PTC Therapeutics. The collaboration focused on a protocol designed to target the B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) protein. This protein is widely overexpressed in tumor cells and acts as an oncogene by regulating the cell cycle genes encoding for p16 and p19 tumor suppressors. Cancer stem cells show that they rely upon BMI-1 protein activity. BMI-1 is a signature gene for diffuse intrinsic pontine glioma (DIPG) specimens tested compared to the matched normal tissue and is a potential therapeutic target to treat children with DIPG and high-grade glioma (HGG). PTC596 is the clinical compound currently in development by PTC Therapeutics as a BMI1 modulator. Investigators anticipate that BMI-1 will inhibit DIPG and pediatric HGG cell growth and sensitize tumor cells to DNA damaging agents, leading to DIPG and HGG cell death. Patients receive the investigational product PTC596 orally, twice-weekly, concomitantly with radiotherapy. Post radiotherapy patients will continue to receive PTC596 twice weekly for up to 26 cycles.
This oncological study to determine the maximum tolerated dose posed many complexities in development for the DMAC team: extensive eCRF casebook design, multiple arms of therapy with a complex schedule of events and study design, database limitations, extensive table shells (80+) and Standard Data Tabulation Model (SDTM) mapping of the raw data for FDA submission–to name a few. The DMAC team rose to the challenge to meet the needs of the study; data managers, database programmers, and statisticians along with project managers within CBDI worked closely together to produce quality output to meet not only the needs and demands of the study but also those of the stakeholders–the investigator and the drug sponsor.
We are hopeful that the relationship established with this project can serve as a springboard for future collaborations with the CBDI team. Additionally, DMAC demonstrated it's capabilities to partner with pharmaceutical and medical device companies on FDA submission projects.
Psychometric Evaluation of the Clinician Administered PTSD Scale for DSM-5 and the PTSD Symptom Scale Interview for DSM-5 in an Active Duty and Military Veteran Sample
Established by Congress in 2007, the Psychological Health and Traumatic Brain Injury Research Program (PH/TBIRP) seeks to prevent, mitigate, and treat the effects of traumatic stress and traumatic brain injury on function, wellness, and overall quality of life for service members as well as their caregivers and families. The Cincinnati Veterans Affairs (VA) Medical Center is participating in this program by evaluating the psychometric properties the CAPS-5 and PSSI-5 assessment tools in active duty military personnel and veterans and comparing the CAPS-5 to the previous gold-standard tool, the CAPS-IV. The task of the DMAC is to create the statistical analysis plan (SAP) and the SDTM specs for this study.
This project will underscore DMAC's capabilities in providing statistical support and creating CDISC-compliant datasets for psychometric assessments.
Every Child Succeed (ECS) Biorepository
Katherine Bowers, PhD, MPH, and Ted Folger, PhD, MS, received an Academic and Research Committee (ARC) Award to develop a birth cohort biorepository of multiple samples provided by mother-infant dyads participating in Every Child Succeeds (ECS), a home visiting program serving Greater Cincinnati and centered at Cincinnati Children's. Maternal samples include a saliva sample to isolate both DNA and RNA along with a hair and/or nail sample. Infants will provide a buccal cell sample (for DNA and RNA), a nail sample and a stool sample. The biorepository will include collected samples from the home and include multiple dust wipes to measure lead and a vacuum dust sample with the potential to measure allergens, molds, pesticides, pollutants, and environmental microbiome.
In addition to banking samples for future research, there will be pilot analyses conducted on the first 75 mother-infant dyads and their homes. Analyses include epigenome-wide DNA methylation on infant buccal cell DNA, cortisol accumulation from maternal hair and nail and infant nail samples, 16s or metagenomic shotgun sequencing of both infant stool DNA and environmental microbiome from home dust, home dust lead analyses, and identification of several allergens.
American College of Epidemiology Annual Meeting
DBE played a critically important role in the organization of the Annual Meeting of the American College of Epidemiology held in Cincinnati on September 23-25, 2018. The theme of the conference was “Applying Epidemiology Across the Lifespan to Improve Health Care, Inform Health Policy and Enhance Population Health.” The goal of the meeting was to highlight priority areas across the lifespan where epidemiology can advance population health using translational approaches and discuss experiences that can serve as models for intervention. Maurizio Macaluso, MD, DPH, director of DBE, served as the local host and chaired the program committee. Dr. Vincent Felitti, MD, the primary investigator of the Adverse Childhood Experiences Study, was the keynote speaker. Plenary sessions covered the role of epidemiology in precision public health, the epidemiology of addiction and the opioid epidemic, and the role of environmental exposures as determinants of health through the lifespan. Breakout sessions on the Learning Health System, the obesity epidemic, emerging and re-emerging infectious diseases, adult-age consequences of childhood diseases, and dynamic prediction methods, the program was a crowd pleaser: about 200 epidemiologists and public health researchers from across the nation attended the conference. The meeting increased the standing of DBE, Cincinnati Children's and University of Cincinnati before the national community of epidemiologists in academia, government, and industry. DBE faculty, in collaboration with national and international collaborators, showcased their knowledge of methodologic advances by offering pre-meeting workshops and coordinating meeting sessions. Methods-oriented workshops covered joint modeling of longitudinal and survival data, clinical data management, analysis of geocoded data and reproducible research using R, and advanced graphic development in SAS.Rare Diseases Clinical Research Network Coordinating Center
The National Center for Advancing Translational Sciences (NCATS) awarded Cincinnati Children's a five-year, $28 million grant to support the Data Management and Coordinating Center (DMCC) for the Rare Diseases Clinical Research Network (RDCRN). This is the third largest grant ever received by Cincinnati Children’s. Eileen King, PhD, Division of Biostatistics and Epidemiology; Maurizio Macaluso, MD, DrPH, director, Biostatistics and Epidemiology; and Peter White, PhD, director, Division of Biomedical Informatics co-lead the center.
In the United States, a disease or disorder is “rare” when it affects fewer than 200,000 people at a given time. Overall, there are about 7,000 rare diseases affecting 25-30 million people in the U.S. In 2002, Congress enacted legislation authorizing the National Institutes of Health to launch the Rare Diseases Clinical Research Network (RDCRN). The network has grown to support hundreds of studies via approximately 20 “consortia” focusing on specific types of disease. Two hundred eighty-eight sites conduct this research across the US, Canada, the UK, France, Italy, Japan, Australia, and 16 additional countries. These studies involve more than 40,000 patients, including rare cancers, heart and lung disorders, and diseases of brain development. The DMCC at Cincinnati Children’s serves as the centralized source for data storage and sharing for RDCRN. It provides access to a wide range of more-standardized clinical, molecular and genomic data along with clinical images and other forms of data, all of which is available in order to conduct more robust studies.
For families and physicians, this work will help accelerate rare disease research, eventually leading to more clinical trials of new medications, improved diagnostic technologies, and other innovations to improve and extend lives. One of our goals is to improve our outreach to the rare diseases community. We want input from patient advocacy groups and treating physicians to inform study design, to better disseminate results, and to influence clinical practice and policy. This project underscores Cincinnati Children’s commitment to expert data coordination and management, biostatistics, epidemiology and informatics as indispensable disciplines for advancing pediatric research and care. It offers a significant opportunity for our institution to lead research across the nation and touch the lives of millions who live with rare diseases.
