FDA changes lithium label to reflect appropriate dosing for children

The U.S. Food and Drug Administration (FDA) recently updated the label for the drug lithium to include appropriate dosing for children. The change was made after a trial supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) showed that lithium was safe and effective for children with bipolar disorder. Prior to this change, lithium had no safety or dosing information for anyone under age 18.

Researchers enrolled 81 children ages 7 to 17, who were divided into two groups. Fifty-three received lithium for a period of 8 weeks, and 28 received a placebo. Based on a questionnaire, researchers found that children receiving lithium experienced improved symptoms over those in the placebo group. In addition, children taking lithium did not experience significant metabolic side effects such as weight gain, as compared to other medications for bipolar disorder.

The Best Pharmaceuticals for Children Act (BPCA), which became law in 2002, funds research on medications for infants and children. The PTN was created by NICHD to make these pediatric trials more efficient. Read more on the NICHD website.

Database locked for SCAMP study

The Pediatric Trials Network (PTN) has locked the database for the Antibiotic Safety in Infants with Complicated Intra-abdominal Infections (SCAMP) study. The study, which enrolled its first patient in 2014, is designed to assess the safety, efficacy, and pharmacokinetics of three commonly prescribed antibiotic regimens for infants with intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are common and often fatal in premature infants. The most common cIAI in neonates is necrotizing enterocolitis (NEC), a devastating disease that causes inflammation and can eventually destroy the wall of the bowel.

“In extremely low-birth-weight infants, the death rate for NEC can be as high as 50 percent,” said Dr. Michael Smith, investigator for the SCAMP study and associate professor of pediatrics at the Duke University School of Medicine. “Even survivors can suffer from lifelong complications such as short bowel-syndrome and poor neurodevelopmental outcomes.”

The most commonly used antibiotics in infants with cIAI include ampicillin, metronidazole, clindamycin, piperacillin-tazobactam, and gentamicin. However, since safety and efficacy data are lacking, these drugs are not labeled for use in infants with cIAI.

The PTN is filling this information gap with SCAMP, a partially randomized, multicenter, open-label study to determine the safety of these drug regimens in this specific and highly vulnerable population. Nearly 300 infants participated in the study at 58 sites in the U.S. and Canada. The infants were enrolled for 100 days, including 10 days of treatment and up to 90 days of follow-up assessments.

As a next step, the results of the SCAMP study will be submitted to the FDA for potential drug label changes.

PTN intern credits experience in STAR Program with passion for medical research

Daniel Gorham was a 17-year-old high school student when his mother, a data scientist at the Duke Clinical Research Institute, showed him an article about the Summer Training in Academic Research (STAR) Program.

Although he dismissed the idea at first, he began reading up on the program and became more intrigued. He applied in 2016, and it is a decision he doesn’t regret.

“I always knew I wanted to do something in the sciences, but I didn’t know which route I wanted to take,” he said. “Learning about the different career fields and meeting different doctors and professionals, I ended up learning more about myself.”

The annual STAR Program gives high school students, college students, and middle and high school teachers hands-on experience conducting an original research project. It also provides classroom training in epidemiology, global health, medical ethics, statistics, and writing.

Although Gorham was initially more interested in cancer research than pediatrics, the eight-week program changed his mind. He spent the summer researching bronchopulmonary dysplasia (BPD), a dangerous lung disease that affects approximately 17,500 premature infants in the U.S. every year, often leading to life-long medical problems and even death.

His research on how BPD impacts the lives of premature infants, along with lectures in neonatology and tours of the neonatal intensive care unit (NICU), quickly instilled a love of pediatrics. The fact that Gorham’s older brother had been born preterm made the research hit even closer to home.

“I had always heard these stories about how tiny and sick he was, and how his chances of life were so slim,” Gorham said. “After spending time on rounds and being around these babies and their families, I realized how important this work really is.”

After graduating from the program, Gorham kept in close contact with program director Dr. Danny Benjamin. When an opening became available for a summer intern at the Pediatric Trials Network (PTN), where Benjamin is principal investigator, Gorham jumped at the chance.

For the entire summer, he conducted research on blood plasma stability, or how certain drugs stay stable in the blood of infants and children. At the end of his internship, he presented his findings on 70 different drugs to an audience of doctors and other professionals at the DCRI.

Gorham is now returning to East Carolina University, where he will be a junior this year. After completing his degree, he plans to come back to Durham to take the next steps toward a career in pediatric research.

“When I say the STAR Program changed my life, it sounds cliché,” he said. “But without it, I would have ended up approaching a career that I didn’t have much passion for.”

He recommends the STAR Program to others, and has even encouraged three of his friends to apply.

“It takes you out of the mindset of a high school student and turns you into an adult,” Gorham said. “My outlook on science completely transformed from, ‘I need to get an A in this class’ to ‘This actually saves lives.’”

PTN creates data repository to aid in pediatric research

Dr. Christoph Hornik

Randomized clinical trials are considered the gold standard in clinical research. However, they often require a great deal of time and cost, and may not be feasible to conduct in vulnerable populations such as premature infants.

To overcome these difficulties, the Pediatric Trials Network (PTN) developed a repository of electronic health record (EHR) data gathered from nearly 265,000 pediatric patients to better guide research.

“This real-world data can be used to target drugs, conditions, and subpopulations for clinical studies that will maximize public health benefit and help identify areas for future study,” said Dr. Christoph Hornik of the Duke Department of Pediatrics, who led the development of the data repository.

The Best Pharmaceuticals for Children Act (BPCA) mandates the National Institutes of Health to prioritize areas where there is a critical need for information to guide medical treatments in children. With funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the PTN conducts studies designed to determine the dosing, safety, and efficacy of drugs that have been approved for adults but lack information for the pediatric population.

The repository, which includes data collected from 9 participating sites from 2013 to 2017, will aid in PTN’s mission by providing a multicenter data source to support its studies. It will facilitate both trial planning and the analysis of the uses and effects of a variety of medications in infants and children.

“Findings from this initiative will benefit children receiving care by not only shedding light on existing treatment practices, but also determining best practices for the future,” Hornik said.

The data collection, validation, and storage process was managed by Duke Health Technology Services and conducted in accordance with the Federal Information Security Management Act.