OneFlorida teams receive PCORI funding to scale up research on rare diseases

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Researchers at the OneFlorida+ Clinical Research Network are using big data analytics to scale up research and boost care and treatment options for people affected by three potentially debilitating rare diseases.

OneFlorida+ study teams at UF Health will conduct comparative effectiveness research on preserving kidney function in children with chronic kidney disease and treating rare neuroendocrine cancers in adults.  A team of scientists at Nicklaus Children’s Hospital in Miami will evaluate treatment and care options for children with a rare form of epilepsy known as Lennox-Gastaut syndrome.

All three of these studies are funded by the non-profit Patient-Centered Outcomes Research Institute (PCORI), which has made rare disease research one of its funding priorities.

Rare diseases are often chronically debilitating and sometimes life threatening.

“Treating and caring for people with rare diseases poses many challenges,” said François Modave, Ph.D., associate professor and director of artificial intelligence and decision-making in the department of health outcomes and biomedical informatics at the UF College of Medicine. “Because the number of people affected by any given rare disease is so small, research funding and other resources are often in short supply,” he said.

The small number of patients affected also makes it hard for researchers and clinicians to develop and test new treatments. Clinical trials needed to test the safety and effectiveness of a new treatment typically require large numbers of study participants to produce reliable results.

According to the U.S. Centers for Disease Control and Prevention, about 25 million Americans are affected by rare diseases—medical conditions that affect fewer than 200,000 people nationwide.

Although the number of affected individuals for any particular rare disease may be small, the total number of Americans diagnosed with rare diseases is nearly 10 percent of the U.S. population—about the same as the number of Americans with diabetes.

“Most rare diseases are not studied enough,” Modave said. As a result, patients with rare diseases often undergo years of testing before they are properly diagnosed, and many receive ineffective treatments that haven’t been adequately tested.

The three OneFlorida+ studies are part of PCORI’s $48 million 2021 Conducting Rare Disease Research initiative and will use PCORnet’s national repository of electronic health records for 66 million patients as tools to identify and enroll patients and to analyze data.

PCORnet’s national network of eight regional clinical research networks—including OneFlorida+ —provides researchers with the ability to study conditions affecting even small numbers of people while maintaining confidentiality of protected health information and patient privacy.

Modave said these studies provide just a few examples of how data science, big data analytics and artificial intelligence are fundamentally changing the way scientists conduct health research. By pooling electronic health records and other data into a central location and applying data analytics and AI tools, scientists are now able to conduct health research on a scale that simply was not possible even 10 or 15 years ago, and at a much faster pace.

PCORnet’s national network of eight regional clinical research networks—including OneFlorida+ —provides researchers with the ability to study conditions affecting even small numbers of people while maintaining confidentiality of protected health information and patient privacy.

In the past, for example, locating the small numbers of patients with rare diseases to participate in clinical trials may have involved using advertisements, fliers and other methods to get the word out, and paying trained medical staff to spend countless hours manually searching through tens or even hundreds of thousands of medical records.

“The work was labor-intensive, extremely slow and very expensive—like looking for a needle in a haystack,” Modave said. “Now, we can develop sophisticated search queries known as computable phenotypes that enable computers to comb through the electronic health records of millions of patients with incredible speed and help us locate the small number of patients affected by these rare diseases in a matter of hours.”

By tapping into the OneFlorida+ Data Trust, a repository of secure electronic health records for millions of patients in Florida and select cities in the Southeast, researchers at UF Health and OneFlorida+ hope to quickly identify and enroll patients in these studies. The researchers also will use electronic health records to evaluate the effectiveness of various treatments on health outcomes.

UF Health serves as the coordinating center for the OneFlorida+ Clinical Research Network, which includes 12 academic centers and health systems across Florida, together with Emory University in Atlanta and the University of Alabama at Birmingham. OneFlorida’s network of 22 hospitals, 1,240 practices/clinics and 4,100 providers care for about 74% of Floridians in all 67 counties and in select metropolitan areas of Georgia and Alabama. OneFlorida is also one of nine clinical research networks nationwide participating in PCORnet, the national patient-centered clinical research network.

The Studies

PRESERVE-Preserving kidney function in children with chronic kidney disease

François Modave, Ph.D., an associate professor and director of artificial intelligence and decision-making in the department of health outcomes and biomedical informatics at the UF College of Medicine serves as the UF Health site-principal investigator of PRESERVE, a nationwide study to assess how well different strategies to monitor and treat high blood pressure can preserve kidney function in children with chronic kidney disease.

Fewer than one in 15,000 children are affected by chronic kidney disease, a condition characterized by reduced kidney function for three months or longer. Over time, progressive loss of kidney function leads to end-stage kidney disease, which requires long-term dialysis or a kidney transplant. The most important treatment goal for affected children is to preserve kidney function, and controlling blood pressure with medication plays a crucial role.

François Modave, PhD
François Modave, PhD

The PRESERVE study will use electronic health records from 2009 to 2022 to compare the effectiveness of various strategies for monitoring and treating high blood pressure on preserving kidney function. The researchers will also survey 800 children with chronic kidney disease and their parents using an electronic questionnaire to assess how management of blood pressure affects patients’ pain, fatigue, sleep, emotions, relationships with friends, and satisfaction with their lives.

UF Health is one of 16 health systems nationwide participating in the PRESERVE study, led by Christopher Forrest, M.D., Ph.D., PI of PEDSnet, director of the Center for Applied Clinical Research at the Children’s Hospital of Philadelphia Research Institute, and professor of pediatrics at the University of Pennsylvania Perelman School of Medicine.  Michelle Denburg, M.D., M.S.C.E, a pediatric nephrologist, director of research for the Division of Nephrology at the Children’s Hospital of Philadelphia, and an associate professor of pediatrics and epidemiology at the University of Pennsylvania Perelman School of Medicine, is co-PI of the PRESERVE study. 

About 11,000 children nationwide are expected to participate in the study, making it the largest study to date on children with this rare condition who have not yet reached end-stage kidney disease. Study results will address important questions about blood pressure management for patients with chronic kidney disease, their families, and their clinicians.

Improving treatment for people with neuroendocrine tumors

Another UF Health researcher, Yi Guo, Ph.D., serves as the UF Health site PI for the “Comparative Effectiveness Research for Neuroendocrine Tumors,” or CER-NET study. Guo is an assistant professor in the department of health outcomes and biomedical informatics at the UF College of Medicine and a member of the UF Health Cancer Center.

Yi Guo, Ph.D.
Yi Guo, PhD

The CER-NET study will evaluate the optimal sequence of administering existing drug therapies available to patients, with the goal of maximizing drug effectiveness and minimizing toxic side effects.

Currently about 180,000 adults in the U.S. are living with neuroendocrine tumors, or NETs, which frequently occur in the gastrointestinal tract, pancreas and lungs. These slow-growing tumors produce vague signs and a variety of symptoms, often leading to delayed diagnoses. For about half of the patients, by the time the cancer is diagnosed, it has already spread to other parts of the body. Once the cancer has spread, surgical removal of the tumor isn’t enough to bring about a cure. But many tumors respond to long-term treatment with a class of drugs known as somatostatin analogues (SSAs), which slow down the production of hormones such as serotonin and help control symptoms.

When those drugs stop working, a number of other therapies are available to patients, but there’s no clear guidance on which therapy would be best to try next, or which treatment options may be closed off to patients in the future as a result of earlier treatment decisions they made. The goal is to evaluate these therapies and work closely with patients and their doctors so they can tailor treatment to the type of tumor the patient has and make more informed decisions about their treatment.

In keeping with PCORI’s mission of engaging patients and their families as partners in clinical research, patients will be enrolled through an online patient portal that’s co-produced by NET patients.

UF Health will recruit about 215 of the 3,000 patients in the CER-NET study. Other UF researchers involved in CER-NET include Jiang Bian, Ph.D., an associate professor of biomedical informatics, who will serve as OneFlorida site lead informatician; and Brian Ramnaraign, M.D., an assistant professor of medicine in the division of hematology and oncology at the University of Florida College of Medicine, who will serve as site clinical investigator. The national multi-site study is led by Michael O’Rorke, Ph.D., an assistant professor in the University of Iowa College of Public Health.

Reducing the health impacts of a rare form of epilepsy

Daria Salyakina, Ph.D., director of personalized medicine and health outcomes research at Nicklaus Children’s Research Institute in Miami, will serve as site principal investigator (PI) for PCORI’s “Comparative Effectiveness of Palliative Surgery versus Additional Anti-Seizure Medications for Lennox-Gastaut Syndrome” study. This serious and ultra-rare form of epilepsy begins in infancy and early childhood, resulting in frequent trips to the emergency room and emergency hospitalizations. Because seizures begin at a very young age, Lennox-Gastaut syndrome usually leads to severe disabilities in gross motor, fine motor, communication, eating and other important skills needed for daily functioning.

Daria Salyakina
Daria Salyakina, PhD

The study, led by Anne Berg, Ph.D., and Sandi Lam, M.D., MBA, at the Ann & Robert H. Lurie Children’s Hospital of Chicago, will engage a network of pediatric hospitals in the United States where children with Lennox-Gastaut syndrome are cared for, including Nicklaus Children’s Hospital. The researchers will examine whether using additional anti-seizure medications or adding palliative surgery to existing medications reduces seizure-related emergency department visits and hospitalizations.

The study will also document the use of surgical or medical treatment approaches across 18 pediatric hospitals in the United States, and explore whether surgery or medication leads to different outcomes for children depending on their age, medical fragility, ethnic or racial background and insurance type.

Study results will help parents and providers make more informed choices about treatment for children with Lennox-Gastaut syndrome and will highlight areas for improvement in providing the best possible health care for this severe, lifelong disorder.

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