Going it alone is a no-go when it comes to making discoveries about rare diseases, a category that includes most serious pediatric diseases. No single pediatric institution usually has enough patients to generate large numbers of study participants, so research networks that provide access to diverse, nationally representative health information from millions of children are key to accelerating scientific discovery by facilitating a range of study designs and efficient study processes. A leader in many such networks, Children’s Hospital of Philadelphia has received several new opportunities just in the last year to advance collective efforts against rare and chronic pediatric diseases.

PEDSnet, a clinical data research network that combines clinical data from eight children’s hospitals, including CHOP, plus several specialty disease networks, received $8.6 million in funding to continue its discovery and implementation of new ways to provide the best care and outcomes for children. PEDSnet is one of 13 clinical data research networks under the umbrella of PCORnet: the National Patient-Centered National Clinical Research Network. The three-year grant from the Patient-Centered Outcomes Research Institute (PCORI), an independent nonprofit organization based in Washington, D.C. which also oversees PCORnet, allowed PEDSnet to enter its second phase in its second year, integrating data from each of its members.

“With our first phase of funding, PEDSnet developed infrastructure for rapid learning with observational studies and clinical trials,” said CHOP’s Christopher Forrest, MD, PhD, who is the principal investigator of PEDSnet and a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and was also named chair of the research committee for PCORnet in 2016. “This second phase of funding will enable PEDSnet to reach a high level of operational excellence, ultimately moving into a sustainable research network that advances children’s health through faster and cheaper clinical research.”

Dr. Forrest’s work as principal investigator of PEDSnet will benefit another major initiative he leads as Steering Committee Chair, the Validation of Pediatric Patient-Reported Outcomes in Chronic Diseases (PEPR) Consortium. The PEPR consortium was launched with grants from the National Institutes of Health in September 2015 to advance the science of patient-reported outcome measures. The effort aims to validate standardized patient survey tools so that patients’ own reports of outcomes such as fatigue, stress, and positive affect can be quantified and compared over time and across study populations in the same way that blood pressure, cholesterol, and other lab test results can be compared today. CHOP is a leader of one of four centers receiving NIH PEPR awards and serves as the consortium’s administrative leader, supporting resources and technical expertise for projects undertaken by PEPR investigators at the other three centers. The infrastructure developed under PEDSnet offers a data management platform and standardized data formats and sharing for PEPR research data.

Read more about the PEDSnet Phase 2 award and the PEPR Consortium on Cornerstone.

Accelerating drug discovery for pediatric cancers through robust preclinical testing is essential to translate genomic discoveries into targeted therapies. Preclinical testing provides reliable data for scientists to decide which agents to test in human clinical trials. Children’s Hospital of Philadelphia’s involvement as one of four centers in the new Pediatric Preclinical Testing Consortium (PPTC) launched by the National Cancer Institute aims to help researchers identify more effective treatments for children with cancer.

Pediatric oncologist John M. Maris, MD, who leads CHOP’s research program within the PPTC, focuses on forms of neuroblastoma that are at high risk of treatment failure despite chemotherapy, radiation therapy, and immunotherapy. Neuroblastoma is a tumor of nerve tissue that develops in infants and children. Dr. Maris’ laboratory has created preclinical models of neuroblastoma that incorporate genetic material from patient tumor cells. Because neuroblastoma is particularly complex and variable, this approach allows scientists to understand the unique genetics of a patient’s tumor and develop patient-specific therapies that target a cancer’s vulnerabilities while sparing healthy cells.

“Before testing a drug in children, we need a scientific basis for using it, based on deep understanding of the biology involved, and supported by promising results in cell and animal models,” Dr. Maris added. “These preclinical findings will provide stronger evidence for us to engage proactively with drug companies who could partner in developing these drugs.”

Dr. Maris also envisions that preclinical research will lead to rational drug combination strategies for more effective treatments, rather than a reliance on single agents. Dr. Maris is collaborating on this project with CHOP co-investigators Yael P. Mossé, MD, Kateryna Krytska, and Matthew Tsang. The other centers in the PPTC, selected like CHOP after a highly competitive process, focus on leukemia (Lowy Cancer Research Center, Australia), brain tumors (Texas Children’s Hospital), osteosarcoma (tumors in bone; The Children’s Hospital at Montefiore, New York), and other sarcomas and kidney tumors (Greehey Children’s Cancer Research Institute, San Antonio, Texas).

Big problems require big thinkers. That is why the Center for Autism Research (CAR) at Children’s Hospital of Philadelphia teamed up with 20 other medical institutions in a new online initiative dubbed SPARK, designed to become the largest autism study ever undertaken in the U.S.

Sponsored by the Simons Foundation Autism Research Initiative, SPARK (stands for Simons Foundation Powering Autism Research for Knowledge) will collect information and DNA for genetic analysis from 50,000 individuals with autism and their families. Autism spectrum disorder has a strong genetic component, researchers say, but while 65 genes that definitely play a role in autism have already been identified, scientists estimate about 300 or more are involved.

“Identifying genes is critically important for developing new therapies for autism; however, one of the greatest challenges for researchers is the sheer number of gene variants associated with autism, combined with the tremendous variability in the symptoms and manifestations of autism,” said Robert T. Schultz, PhD, director of CAR and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, who is leading CHOP’s research site in the study along with clinical neuropsychologist Juhi Pandey, PhD, a senior scientist at CAR and clinical assistant professor of Psychiatry at the Perelman School of Medicine. “In order to begin to see a pattern of genetic causes, extremely large samples of patients are needed for research. Team science and collaboration is the only viable path forward for rapidly making progress, and SPARK provides us with just such an opportunity.”

Within less than a year from its kickoff in February 2016, the SPARK network collected samples from more than 10,000 people, with approximately 2,500 of those coming from the CHOP site.

For more information, visit www.SPARKforAutism.org/CHOP. To learn about other areas of CAR research, visit www.centerforautismresearch.org.

Children’s Hospital of Philadelphia is leading a $1.8 million multicenter study to shed light on how physicians could safely approach patient discharge scenarios after children with acute myeloid leukemia (AML) receive a course of chemotherapy at a hospital, while also considering family preferences.

During the periods following treatment, pediatric cancer patients can have a difficult time fighting off bloodstream infections and related complications. Because of this risk, some physicians prefer that children with AML stay in the hospital for close monitoring after treatment. Other doctors allow patients to go home and return to the hospital if a fever occurs. However, physician-researchers do not have enough evidence to know with certainty if patients are better off remaining in the hospital or going home with their families.

The study, entitled “Home or Away From Home,” will compare 490 patients’ medical records to determine the risks/benefits of outpatient vs. inpatient management of neutropenia in children with AML. Fifteen pediatric hospitals from across the U.S. will participate. In addition to collecting data so that the study team can compare each discharge strategy’s medical outcomes including bloodstream infection and delays in subsequent courses of chemotherapy, several sites also will assess patient outcomes by surveying patients and families about their quality of life.

“We are very excited about this highly collaborative study that we hope will help us improver our care for children with acute myeloid leukemia,” said Richard Aplenc, MD, PhD, a CHOP pediatric oncologist and AML researcher and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania who is the principal investigator of the three-year study funded by the Patient-Centered Outcomes Research Institute.

Dr. Aplenc also was recognized in March by Hyundai Hope on Wheels with a $1 million Hyundai Quantum Award to advance his work on innovative immunotherapy approaches. The new grant will enable his team to identify specific proteins on the outside surface of AML cells that could be the most appropriate targets for immune cells programmed to attack cancers.

“This award will help CHOP physicians and their collaborators develop new therapies for children with AML that has not responded to current therapies, or has relapsed despite those therapies,” said Stephen Hunger, MD, chief of the division of Oncology and director of the Center for Childhood Cancer Research at CHOP and professor of Pediatrics at the Perelman School of Medicine.