Research conducted by the Pediatric Trials Network (PTN) has led the U.S. Food and Drug Administration (FDA) to update the prescribing information, or drug label, of acyclovir to include dosing for infants with Neonatal Herpes Simplex Virus (HSV) based upon the infants post-menstrual age. Acyclovir (brand name Zovirax) is an antiviral drug used in the pediatric population to treat HSV, a highly contagious virus that can be very serious for babies.
Because an infant’s immune system is not fully developed to fight off the virus, the disease can result in death or mental disabilities. While appropriate dosing of acyclovir was known for adults and children, acyclovir had not been adequately studied in full-term or preterm infants.
In the two associated PTN studies, 32 infants were enrolled. The first study was conducted at a single medical center in preterm and term infants with suspected HSV infection. The second study involved multiple medical centers and enrolled only preterm infants with suspected HSV infection.
Based upon the pharmacokinetic (how a drug travels through the body) results, the FDA updated the label to include dosing in infants based on their post-menstrual age (PMA), or the time that had elapsed since the mother’s last menstrual cycle. PMA is especially useful in preterm infants because it characterizes the baby’s expected developmental age.
With a nearly 30-year history in academic research, Dr. Christine Turley offers a variety of perspectives into the world of clinical research. After a start in private practice, Dr. Turley went on to spend a large portion of her career in vaccine research and development. A general pediatrician by trade, Dr. Turley currently serves as director of the Research Center for Transforming Health at the University of South Carolina. The mission of the center is to help investigators and their teams conduct transformative research by helping overcome barriers that are often present in newer research settings.
Prior to her current position, Dr. Turley served in a variety of roles at the University of Texas Medical Branch (UTMB) in Galveston, Tex. She worked in clinical education, was the vice chair of Clinical Programs, and was heavily involved in the institution’s clinical operations.
She is currently involved in the administration of the Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (PTN POPS) study at the University of South Carolina. We recently spent time discussing the importance of the study as well as clinical research in general.
Q: How would you explain the importance of clinical research, specifically for children?
A: We treat children every day and we try to treat them with the best evidence possible. But what we’re realizing is that, in many cases, the evidence is limited. In many cases we’re treating based on experience instead of data. The other thing about research, specifically in children, that is really important is that many chronic diseases originate in childhood. Our opportunity to help prevent this trajectory has never been more compelling than it is now. It’s too late to start working on hypertension when people are 50. We’re realizing now that it’s better to start at the very beginning of a person’s life.
Q: Why should people care about the findings of the PTN POPS study?
A: Over time, we’ve seen the level of variability that exists in children. The physiology of children changes very much over the child’s lifespan. It may seem obvious, but a 17 year old is very different than a seven month old. As we’re using medications on children, it’s important that we get better information so that we’re providing the best care possible and not running the risk of worsening conditions. We know we can do better, and studies like PTN POPS provide us with the opportunity to do better and provide better care for children.
A: ISPCTN is a component of the larger NIH Environmental Influences on Child Health Outcomes (ECHO) program. The IDeA State initiative weaves together the pediatric research community in a very interesting way by including other pediatric investigators and populations that are important, but otherwise may not have an opportunity to participate in ECHO. As a result, the research community becomes much more holistic and places an equal value on all components, creating synergy for pediatric research across the country. The capacity enhancements are wonderful and it’s very gratifying to invite other groups into research that may not have an opportunity otherwise.
Q: What are the benefits of having the University of South Carolina involved in the PTN POPS study?
A: There are three levels at which I see a benefit to USC’s involvement with PTN POPS. The most traditional is that we’ve been able to enroll patients in this study and engage with clinical investigators in other areas. At the bedside level, the teams are very interested in this project because they feel like there is the opportunity to impact patients they see every day. The second benefit is that it has proven the value of research to our group, which is relatively small and young in comparison to others. The third is that it has proven the value of research to our leadership. Even though we’re not enrolling 1,000 kids and making a huge amount of money for our institution, it is extremely relevant to the safety and quality of our care, which we all care about very much.
Paula Delmore has actively participated in the support of clinical research for the past 30 years. Although the majority of her expertise is in the role of site study coordinator, she has served in the roles of multi-site coordinator, sub-investigator, and principal investigator. Her main strengths lie in her attention to detail and solid understanding of clinical trial execution in the neonatal area. Her team routinely performs as a highest enroller, which speaks to her exemplary coordination and good communication with providers, nursing staff, and families. We sat down with Paula to learn more about her work and involvement with the Pediatrics Trial Network.
Q: How long have you worked at Wesley Medical Center and what are your primary responsibilities?
A: I have been at Wesley Medical Center for 40 years and currently work in an administrative role. I supervise nurse practitioners, physician assistants, and support personnel with the Neonatal Intensive Care Unit (NICU).
Q: How does your role as a site coordinator with PTN overlap with your responsibilities as part of the Wesley Medical Center administrative staff?
A: I’ve been working with our Medical Director, Dr. Barry Bloom, for 35 years as a research coordinator. Over time, my role has advanced from being a research assistant to coordinating studies, and at times, being the principal investigator. I have been the principal investigator for a couple of PTN studies, most recently the PTN Baby TAPE study.
Q: How long has Wesley Medical Center been part of PTN?
A: From the very beginning! We were one of the first centers in the Rapid Start Network. We participated in the Fluconazole Safety study and all the early Pharmacokinetic (PK) Antibiotic studies.
Q: What have you found to be the most rewarding aspect of PTN?
A: PTN covers the gamut of pediatrics, but what I find most rewarding and exciting is that they continue to explore new therapies for neonates, and also validate standard practice where there is no prior evidence.
Q: Is there an experience you’ve had with PTN that has been particularly impactful?
A: Right now we are participating in the Sildenafil II study. As part of that study, it’s really great to work with families and offer them something that could potentially help their baby. Even though everything is an unknown, and we aren’t sure it’s going to help, it’s nice to offer parents the chance that our research and efforts will benefit their child. In general, giving families another option for excellence in care is what I find to be the most impactful.
Q: Why would you recommend other investigators become a part of PTN?
A: The responsiveness of the lead investigators is phenomenal. When questions arise, they are ready and available to answer and are very timely. This allows for the seamless continuation of patient enrollment and helps in meeting the randomization timelines. The PTN studies are some of the most organized and efficient I’ve been a part of.
The Pediatric Trials Network (PTN) was recently awarded a contract by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to design and lead pediatric trials over the next eight years.
“Over the last eight years, we have been able to conduct 26 clinical trials in 13 different therapeutic areas enrolling over 8,000 children, which is more than triple the scope of work that was outlined in the initial NIH contract,” said Daniel Benjamin, Jr., MD, PhD, principal investigator and chair of the PTN.
Benjamin was the original awardee of the NIH contract in 2010. He and the PTN’s program manager, Gary Furda, helped secure the second award for an additional eight years. Additional DCRI faculty supporting the contract include Christoph Hornik, MD; Kanecia Zimmerman, MD; and Michael Cohen-Wolkowiez, MD, PhD.
“Danny and his primary supporters on the faculty side are outstanding in what they do and their passion for improving the health of children is unmeasured,” said Taylor Nguyen, a senior business development associate at Duke who was part of the grant-writing group. “The incredible results that the PTN team has produced over the course of the last eight years are largely due to their commitment and passion and how they go above and beyond in the work they do.”
“In the first eight years of the PTN, we were able to transform neonatal and obesity trials,” Benjamin said. “Over the next eight, we will have people rethink the way drug studies are done for breastfeeding women and mental health for children.”
Benjamin intends for the PTN to lead the way in revolutionizing the way clinical trials are conducted in children.
“We will continue designing larger trials and make these large trials more efficient,” he said. “With all the operational excellence at the DCRI, the junior and mid-career faculty, and our very determined staff at the PTN sites working together round the clock in various capacities and doing exceptional work for the network, no goal is big enough.”
The Summer Training in Academic Research (STAR) Program welcomed 21 participants at its kickoff event today. Now in its sixth year, the program provides hands-on research experience for undergraduate students, high school students, and high school teachers during the summer academic break.
“The STAR program is an excellent way for students to learn more about clinical research and how to effectively work in a collaborative environment,” said program leader Dr. Danny Benjamin, principal investigator for the PTN and faculty associate director of the Duke Clinical Research Institute (DCRI).
During the eight-week program, participants are placed in teams and matched with faculty mentors to work on original, hypothesis-driven projects. Participants also receive intensive instruction in developing scientific manuscripts, applied statistics, and data analysis. A goal of the program is to have every trainee qualify for co-authorship on a peer-reviewed manuscript related to their team’s project.
“I joined the STAR program because I want to be a neurosurgeon one day. Spending time with the STAR program mentors will help me determine if I’m on the right path to achieving my goals,” said Millbrook High school rising senior, Kennedy Hill.
The faculty of the STAR Program is actively involved in research sponsored by the National Institutes of Health (NIH). Combined, these faculty members have more than 200 publications with trainees as either first author or co-author.
In addition to the research project, program participants attend lectures on neonatology, antimicrobial therapy, pharmacoepidemiology, and medical ethics. Eligible students experience clinical medicine firsthand by shadowing a physician on hospital rounds.