Going it alone to create a patient cohort population that is large enough to study can be a time-consuming process for an individual genetic scientist who wants to make a difference in a pediatric disease. That’s why three premier pediatric academic medical institutions — Children’s Hospital of Philadelphia, Cincinnati Children’s Hospital Medical Center, and Boston Children’s Hospital — formed the new Genomics Research and Innovation Network (GRIN) to foster a culture of data sharing.

“The ultimate goal is to have this resource populated with over 100,000 cases that would include individuals’ clinical data at a high resolution, genotyping data, and associated biospecimens so that you can move discovery forward,” said Ian Krantz, MD, an attending physician in the division of Human Genetics at CHOP who serves on GRIN’s executive team.

The new initiative helps to overcome barriers to research in pediatric genomics by addressing the problem of too much data and too little time. A wealth of data is available through electronic health records, clinical trials, and data registries, but it is not feasible for individual researchers to comb through all this information and extract what they need to identify large patient cohorts with deep phenotyping. GRIN aims to make this process more consistent, precise, and seamless for its members by establishing a data trust that will allow for more comprehensive analysis of complex disease.

While GRIN is getting up and running, it currently is only open to investigators at the three member institutions, but the idea is to invite other institutions to join GRIN in the future. Before any investigator dives into this unparalleled resource, GRIN’s scientific committee will vet their research proposals. The network’s sustainability committee also is considering how to handle commercial interest, such as from pharmaceutical companies.

“This is a very valuable resource that could be leveraged for drug discovery and therapeutic trials,” Dr. Krantz said. “Having access to this type of well-characterized and accessible cohort with available biological samples is very appealing.”

One of the challenges to pediatric palliative care research is that no one hospital is likely to have a sufficient number of children with a particular condition to be able to fully explore epidemiologic and health services questions. That is why CHOP and three other hospitals that are part of the Pediatric Palliative Care Research Network are launching an innovative multicenter project called SHAred Data and REsearch (SHARE).

CHOP, Boston Children’s Hospital, Seattle Children’s Hospital, and Children’s Hospitals and Clinics of Minnesota all have “remarkably good” pediatric palliative care programs, according to SHARE Principal Investigator Chris Feudtner, MD, PhD, MPH, director of the department of Medical Ethics at CHOP and director of Research for the Pediatric Advanced Care Team. They will collaborate to build a standardized and organized infrastructure to collect and merge patient- and parent-reported clinical data with hospital administrative data into a SHARE database.

The resulting dataset will provide a wealth of information regarding hospital-based care for a cohort of 800 patients receiving pediatric palliative care, including patient demographic and diagnostic information, patient or parent reported symptoms, and parent reports on their levels of distress and how their goals of palliative care change as their child’s serious illness progresses.

“We will follow them over time to identify distinct patterns of how things play out, and how those patterns affect the ways that they think about making decisions for their child,” Dr. Feudtner said. “All of this will hopefully improve the care the kids get and the outcomes for them, their parents, and family members.”

Dr. Feudtner expects that the collaborative SHARE project will be a catalyst for many future studies using the SHARE data and research infrastructure. He envisions large multicenter studies could be accomplished to perform intervention research — such as drug treatment studies or evaluating bundled therapies for symptom control— and quality improvement work within and across hospitals, such as identifying the best care delivery model to transition patients seamlessly from hospital to home care.

While the heft of concussion research has looked at college-aged and professional athletes, a new $4.5 million grant from the National Institute of Neurological Disorder and Stroke will allow researchers from CHOP and Penn team to study a high school population, for whom there is little available data on injury criteria and thresholds. Their goal: Design evidence-based, diagnostic assessment tools for the clinic and the sidelines, as well as create the foundation for better headgear and other protective equipment.

The biggest strength of the study lies in its collaborative nature. The five-year project combined bioengineering and sports medicine expertise under the leadership of Kristy Arbogast, PhD, co-scientific director and director of engineering for the Center for Injury Research and Prevention at CHOP and a research professor of Pediatrics at the University of Pennsylvania; Christina Master, MD, primary care sports medicine specialist and co-director of the Concussion Care for Kids: Minds Matter Program; Catherine C. McDonald, PhD, RN, assistant professor at the Penn School of Nursing, and Susan Margulies, PhD, formerly a professor of Bioengineering at the University of Pennsylvania’s School of Engineering and currently Wallace H. Coulter Chair of the Coulter Department of Biomedical Engineering (BME) at Georgia Tech and Emory University. Together, the team can take a holistic and thorough view of concussion treatment.

“The research questions being addressed by this project can only be answered by interconnected study across the clinic, the lab, and on the field,” Dr. Arbogast said. “Each component informs the other’s research in important ways.”

Their evidence-based findings will help clinicians move away from subjective symptoms and toward more accurate, evidence-based guidelines for diagnosing and managing youth concussions. The study team will use objective metrics that measure a child’s brain function. Enrolling participants from CHOP’s Concussion Care for Kids: Minds Matter program, the researchers will measure and track the objective metrics of balance, neurosensory processing (such as eye tracking), and cerebral blood flow in adolescents ages 14 to 18 with a diagnosed concussion, and then compare those metrics to healthy controls. The resulting data will facilitate the development of a suite of quantitative assessment tools and guidelines that can help clinicians determine how long a child will take to recover, or when a young athlete can return to play.

The researchers also plan to track the magnitude and direction of head impacts of youth on the sports field. Equipped with head-impact sensors, the high school athletes will go about their play while the researchers take pre-and post-season objective clinical metrics data and analyze head impacts from the sensors. The head impact sensor component of the study will enroll research participants from suburban Philadelphia’s The Shipley School.

Five regional cancer academic treatment centers and two pediatric hospitals announced a collaboration in February 2017 called the Philadelphia Coalition for a Cure (PC4C) that is the nation’s first city-wide brain tumor precision-medicine research partnership to benefit both adult and pediatric brain tumor patients. In time, the PC4C plans to expand treatment to include additional tumor and cancer types.

PC4C member institutions are committed to streamlining research and precision medicine efforts. They include the division of Neurosurgery and Center for Data Driven Discovery at CHOP, Lewis Katz School of Medicine at Temple University, The Perelman School of Medicine at the University of Pennsylvania, Sidney Kimmel Medical College at Thomas Jefferson University, Cooper Medical School of Rowan University, Drexel Neurosciences Institute at Drexel University College of Medicine and The Hyundai Cancer Institute at The Children’s Hospital of Orange County. They will work together and with commercial partners and payers to advance data-driven discovery through the rapid sharing and release of data to the entire research community through open science initiatives.

“Brain tumors are the leading cause of disease-related death in children and more than 20,000 adults are diagnosed each year,” said Jay Storm, MD, chief of the division of Neurosurgery at CHOP. “Working with PC4C, we hope to define a new collaborative clinical and research ecosystem that harnesses partnerships among leading academic centers, commercial partners, and insurers to identify therapies and accelerate discovery.”

PC4C is empowering data-driven discovery and improving treatments for brain tumors through treatments that are individually tailored and specific to the biology of each patient’s tumor, young or old, with the aim of reducing toxic side effects and increasing the therapeutic effectiveness of targeted approaches. All patient-consented data for the PC4C will be accessible to the research community via Cavatica, a biomedical data analysis and storage platform that, for the first time, will integrate adult and pediatric brain tumor data.

“One of the mandates of the PC4C is that all the data has to be shared immediately, in real time,” Dr. Storm said. “As soon as it’s generated, it’s going to be made available to the entire scientific community in a protected cloud environment that anyone can access. This kind of sharing is clearly a paradigm shift for academic medicine.”

Our paths to discovery intersect in unexpected ways, and exciting opportunities for research collaboration are around every corner. Two of the most highly regarded autism and pediatric injury research centers in the world are new neighbors at our Roberts Center for Pediatric Research building, and they worked together to study the driving safety of adolescents with autism spectrum disorder (ASD).

The Center for Autism Research (CAR) studies the causes and mechanisms of ASD and develops evidence-based clinical and behavioral interventions across the lifespan, while providing real-world support for individuals and families living with autism here and now.

As part of its mission, the Center for Injury Research and Prevention (CIRP) identifies causes of traffic-related injury and death, then works to translate the research into practical tools and guidelines for families, professionals, and policymakers.

These two premier centers put in motion a research project to begin to learn more about the proportion of adolescents with ASD who get licensed and the rate at which they progress through Graduated Driving Licensing. Their findings showed that as many as one in three teens with ASD without intellectual disability get licensed by age 21, and the results will lead to a new line of research about how to best support families in making that decision to have their children with ASD pursue a driver’s license and to become safe drivers.

In addition to studying injury risk and interventions for individuals with ASD, CIRP is expanding its collaborative work with other CHOP research centers to learn how other developmental and intellectual conditions affect driving safety, such as attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder.

A new Urinary Stone Disease Research Network (USDRN) that includes CHOP will perform the largest studies on urinary stone disease to date, and it has opened the Prevention of Urinary Stones with Hydration study (PUSH), a two-year randomized trial of a strategy to maintain high fluid intake to decrease stone recurrence among adolescents and adults.

The prevalence of kidney stones disease has nearly doubled in the last 15 years in both adults and children, affecting about one out of 11 Americans, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). It also is the most expensive non-malignant urologic condition in the U.S., costing about $10 billion annually. About 10 percent of visits to the emergency department for kidney stones are for repeat encounters.

The PUSH study leaders at the CHOP-Penn Medicine site are principal investigators Gregory E. Tasian, MD, MSc, MSCE, a pediatric urologist and epidemiologist at CHOP; and Peter Reese, MD, MSCE, a nephrologist and epidemiologist at the Perelman School of Medicine at the University of Pennsylvania. They also are senior scholars with Penn’s Center for Clinical Epidemiology and Biostatistics.

“As the largest children’s hospital in the USDRN, CHOP and the Pediatric Kidney Stone Center will contribute substantially to this effort,” Dr. Tasian said. “CHOP has long been a leader in advancing healthcare for children with rare and common diseases. CHOP’s participation in the USDRN will allow us to be at the forefront of decreasing the morbidity of urinary stone disease, which now often begins during childhood.”

The USDRN collaboration also includes the University of Washington, Washington University in St. Louis, University of Texas Southwestern Medical Center, and Duke University. It is supported by the NIDDK.