Cutting the Cost of Clinical Trials by Leveraging Registries

Duke and other CTSA hubs receive NIH grant to use the Society of Thoracic Surgeons Congenital Heart Surgery Database to create a new model for conducting randomized clinical trials in special populations.

September 16, 2016

​Duke has received a National Institutes of Health (NIH) grant to collaborate with other institutions and organizations to design and conduct a “trial within a registry” to improve outcomes after neonatal heart surgery. In doing so, the researchers also plan to create a model for cost-effective clinical trials that leverage existing registry resources.

The $1.3M award will involve Duke University, Johns Hopkins University, and Vanderbilt University – all of which have NIH-funded Clinical and Translational Science Awards. It will also involve the Society of Thoracic Surgeons (STS). Jennifer Li, MD, a pediatric cardiologist, member of the DCRI, and a co-PI for Duke’s CTSA, is the principal investigator at Duke.

Jennifer Li, MD

“Clinical trials are resource-intensive and costly, particularly for special populations such as newborns undergoing heart surgery,” said Li.  “This effort will leverage the existing registry resources of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) to enable us to study the use of steroids after neonatal cardiopulmonary bypass surgery at a fraction of the cost of a typical clinical trial.”

The researchers note that the smaller, widespread populations for patients with rare diseases pose challenges in randomized trial design, recruitment, and analysis. Yet worldwide there are more than 700 active disease registries that have established infrastructure that researchers might be able to use to facilitate clinical trials.

The STS-CHSD has enrolled approximately 98 percent of children undergoing heart surgery in the U.S. from a network of 127 centers for more than a decade. The researchers will use this registry data to ensure the optimal trial design for a study of the use of high-dose system steroids to reduce inflammation in neonates undergoing cardiopulmonary bypass. (The trial is named the STeroids to REduce Systemic inflammation after neonatal heart Surgery – or STRESS trial.) The researchers expect that compared to a traditional trial approach, this method will reduce the cost per patient enrolled by 70 percent.

The three CTSA hubs each bring expertise to the study. Among other skills, Vanderbilt has innovative bioinformatics solutions, Johns Hopkins has leaders for the STS-CHSD, and Duke brings to the table extensive expertise in multi-site clinical trials and is also the data coordinating center for the STS. The trial will also work with patient/parent advocates from the Children’s Heart Foundation.

“The STRESS trial will be the largest ever in neonates with congenital heart disease, and it will answer a clinical question that has persisted for decades,” said Li.

“By collaborating with other institutions and organizations, such as the STS, we will be creating an infrastructure for a national registry-based trials network in children that can serve as a model for other understudied diseases and conditions.”

Other Duke investigators joining Li on this grant include Sean O’Brien, PhD, senior statistician; Kevin Hill, MD, who serves as the clinical lead for the STS-CHSD at DCRI; and Eric Eisenstein, DBA, who focuses on health economics outcomes of patients. The project team will be supported by Rachel Dokholyan and Beth Martinez at the DCRI. The principal investigator from Vanderbilt University is H. Scott Baldwin, MD, division chief of pediatric cardiology. The principal investigator from Johns Hopkins University is Jeffrey Jacobs, MD, director of the Andrews/Daicoff Cardiovascular Program at Johns Hopkins All Children’s Heart Institute. This study is supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number U01TR001803.