Groundbreaking study to assess safety of drugs passed through breastmilk

The Pediatric Trials Network (PTN) is undertaking a groundbreaking study to assess the safety of commonly used off-patent medications when they are given to breastfeeding mothers. The study will track how different drugs are passed through breastmilk to determine dosing levels that are safe for both mom and baby.

Although the U.S. Food and Drug Administration (FDA) has implemented a guidance document on conducting lactation studies, off-patent drugs are not included in that rule. The PTN seeks to fill this knowledge gap.

Dr. Kevin Watt

“Although the benefits of breastfeeding are well-documented, we still don’t know enough about the effects of many prescription and over-the-counter off-patent drugs when they are passed to infants through their mother’s breastmilk,” said Dr. Kevin Watt, an assistant professor of pediatrics at Duke University who is leading the study. “As a rule, we discourage unnecessary drug use during lactation, but it’s quite common for new mothers to have symptoms or medical conditions that must be treated with drugs.”

“Many breastfeeding moms struggle with the decision to take medications because of the fear that these drugs will harm their children,” Watt said. “In the end, it often comes down to either stopping breastfeeding or discontinuing needed medications. We want to take the guesswork out of this decision and allow moms to breastfeed without worry.”

The study is expected to begin in April of 2018 and will enroll approximately 50 lactating women, along with their breastfed infants, for each drug studied. Initially 10 off-patent drugs will be studied, including medications used to treat bacterial infections, depression and anxiety, high blood pressure, diabetes, and chronic pain. Mothers will be enrolled in the study only if they are already taking one of the study drugs as part of their routine care.

Mothers who participate in the study will provide samples of breastmilk, their blood, their infants’ blood, or a combination to help researchers measure drug levels and determine the safest dose. Mothers and infants are expected to remain in the study until the infants reach 180 days of age.

The study, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), will also explore the effects of maternal obesity on drug exposure and long-term outcomes of breastfed infants exposed to drugs in breastmilk.

See the NIH LactMed database for more information on the levels of various substances in breastmilk and infant blood, and possible adverse effects.

15 IDeA sites welcomed into PTN POPS study

Fifteen sites in states participating in the NIH Institutional Development Award (IDeA) program are being onboarded into the Pediatric Trials Network’s (PTN) POPS study of commonly used medications in children.

The IDeA program aims to build research capacities in states that have historically received low levels of NIH funding by supporting research, faculty development, and infrastructure improvements. The IDeA States Pediatric Clinical Trial Network (ISPCTN), a network of IDeA sites established by the NIH’s Environmental Influences on Child Health Outcomes (ECHO) Program, recruits study participants from states whose populations are disproportionately rural and medically underserved.

“Historically, these populations have been underrepresented in multicenter clinical trials and their involvement in this study will provide them an opportunity to participate in clinical research,” said Jeannette Y. Lee, principal investigator for the ISPCTN and Professor of Biostatistics at the University of Arkansas for Medical Sciences. “PTN will also provide the sites with a way of interacting with a large community of clinical trial researchers and a venue for contributing to clinical research.”​

The Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care (POPS) study is designed to better characterize the pharmacokinetics of a variety of commonly used drugs in children and infants for which limited information is available in the pediatric population. More than 70 drugs (36 currently enrolling) used to treat nearly 50 diseases and conditions have been studied so far.

“We are excited to welcome these sites, and feel confident that they will make a vital contribution to the POPS study,” said Dr. Chiara Melloni, co-investigator of the study and Assistant Professor of Medicine at Duke University. “Their participation will allow PTN to expand enrollment and ensure that a more diverse and inclusive population of children is represented in this important study.”

The 15 new study sites are:

  • Alaska Native Medical Center in Anchorage, Alaska
  • Kapiolani Medical Center for Women and Children in Honolulu, Hawaii
  • University of Kansas Medical Center in Kansas City, Kansas
  • Tulane University Health Science Center in New Orleans, Louisiana
  • University of Mississippi Medical Center in Jackson, Mississippi
  • Children’s Mercy Hospitals and Clinics in Kansas City, Missouri
  • University of Montana in Missoula, Montana
  • Dartmouth-Hitchcock Medical Center in Dartmouth, New Hampshire
  • University of New Mexico Health Sciences Center in Albuquerque, New Mexico
  • University of Nebraska Medical Center in Omaha, Nebraska
  • Board of Regents of the University of Oklahoma in Oklahoma City, Oklahoma
  • Rhode Island Hospital in Providence, Rhode Island
  • University of Vermont Medical Center in Burlington, Vermont
  • University of South Carolina in Columbia, South Carolina
  • West Virginia University Hospital in Morgantown, West Virginia

Four IDeA sites are already participating in the study: the Arkansas Children’s Research Institute in Little Rock, Arkansas; the Alfred I. DuPont Hospital for Children in Wilmington, Delaware; the University of Louisville Norton Children’s Hospital in Louisville, Kentucky; and the Medical University of South Carolina Children’s Hospital in Charleston, South Carolina.

Dr. Shakhnovich offers guidelines for prescribing GERD medications to obese kids

 

Dr. Valentina Shakhnovich, Children’s Mercy

When treating gastroesophageal reflux disease (GERD) in obese kids, the common practice of dosing stomach acid blockers based on children’s weight could actually cause more harm than good, said Dr. Valentina Shakhnovich, investigator for the Pediatric Trials Network (PTN) and Associate Program Director for the Gastroenterology Fellowship Research Program at Children’s Mercy Hospitals in Kansas City, Missouri. Shakhnovich shared her research on The Children’s Mercy’s Transformational Pediatrics podcast.

Listen to the podcast here.

GERD, commonly called acid reflux, is a long-term condition in which stomach acid comes back up into the esophagus, causing heartburn, indigestion, and tissue damage. Because the occurrence of GERD is associated with excess weight gain, pediatricians are seeing more cases, as the number of overweight and obese children increases.

Pantoprazole belongs to a class of drugs known as proton-pump inhibitors (PPIs), which have long been used to treat GERD and other conditions related to excess stomach acid. Pediatricians typically dose pantoprazole based on a child’s weight. However, this common practice can actually put bigger kids at risk for unwanted long-term side effects, associated with higher doses of PPIs, such as low bone density and vitamin deficiencies.

“A lot of us have the knee-jerk reaction that if we see a 10-year-old who’s twice the size of an average 10-year-old, maybe we should double the dose,” Dr. Shakhnovich said. “What our research has shown is that’s actually not the best thing to do for obese kids, and it appears that they actually require a lower dose of proton-pump inhibitors than their non-obese counterparts.”

Dr. Shakhnovich suggested including a statement on the pantoprazole label, warning pediatricians not to give more of the drug to overweight and obese children. “Until clear dosing guidelines come from the FDA, think twice before dose escalating just because a child is obese,” she said.

She commended PTN for its awareness of the problem and for leading the way in finding the safest and most effective dose of commonly used medications for overweight and obese children.

“One in 6 children is obese. One in 3 is overweight,” Dr. Shakhnovich said. “It’s essential to start including obese patients in clinical trials so we’re not trying to guess at the correct dose and we’re not trying to play catch-up.”

Sildenafil safety studied for premature infants with bronchopulmonary dysplasia

The Pediatric Trials Network (PTN), with support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is conducting an interventional study to examine the safety and efficacy of sildenafil in treating bronchopulmonary dysplasia (BPD) in premature infants.

BPD is a common chronic lung disease that can affect premature newborns, often leading to life-long medical problems, prolonged hospitalization, and even death. Approximately 17,500 U.S. infants develop BPD each year.

Dr. Matthew Laughon of UNC Hospitals observes infant in NICU

Sildenafil, which is approved for the treatment of pulmonary hypertension in adults, may help improve lung development and is increasingly being used off-label in premature infants with BPD. However, the efficacy and safety of sildenafil in premature infants at risk for BPD is currently unknown.

“Our hope is that this study benefits premature infants and their families by providing more information on the safest and most effective dose of sildenafil to treat this life-threatening condition,” said Dr. Matthew Laughon, principal investigator and neonatologist at the University of North Carolina Hospitals in Chapel Hill, N.C.

The study, Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia, draws on a previous safety study conducted by the PTN from 2013 to 2016. This study enrolled 34 infants of less than 28 weeks gestational age who were receiving sildenafil to treat BPD. Health care providers administered varying doses of sildenafil and collected plasma samples to determine the optimal starting dosing for sildenafil in premature infants.

The current study is expected to enroll approximately 120 infants and will be guided by dosing data from the previous phase 1 safety study. The first study site, Golisano Children’s Hospital at the University of Rochester Medical Center in Rochester, N.Y., was activated Jan. 2 and is currently recruiting participants.

 

PTN captures valuable anthropometric data for infants

The Pediatric Trials Network (PTN) conducted a study in 2015 to capture anthropometric data on pre-term and full-term infants up to 90 days old. An article on the study, An Anthropometric Survey of U.S. Preterm and Full-Term Neonates, was published in the journal Annals of Human Biology last month.

Dr. Susan Abdel-Rahman

“Anthropometric data are invaluable for informing the development of pediatric growth charts, assisting in policy making decisions, and supporting health initiatives,” said the article’s lead author, Dr. Susan Abdel-Rahman of Children’s Mercy Hospitals and Clinics in Kansas City, Missouri. “However, only a limited set of measures are available in publicly accessible databases.” These measures typically include weight, length, and head circumference of infants.

The PTN study captured additional measurements, such as humeral, ulnar, femoral, tibial, and fibular lengths, as well as mid-upper arm, mid-thigh, chest, abdominal, and neck circumference. More than 2000 infants were involved in the ­­study at 8 U.S. medical centers from February to December 2015.

The data generated through the study can be used as indicators of nutritional status, predictors of morbidity and mortality, and can serve as proxy measurements when total body weight is difficult to obtain by traditional means.

“Weight is the single most important predictor of newborn mortality and an essential piece of information for therapeutic decision-making,” Dr. Abdel-Rahman said. “Though a weighing scale remains the universal gold standard for obtaining weight, there exist a number of settings wherein access to a functional, calibrated scale is limited.”

Dr. Abdel-Rahman subsequently used the data to develop a weight estimation strategy for infants in cases where scales are unavailable, or when their use is impractical, such as when infants are connected to monitoring or life-support equipment in the neonatal intensive care unit. The related publication, A Weight Estimation Strategy for Preterm and Full-term Infants, was recently published in Global Pediatric Health. A separate PTN study is currently evaluating a prototype of this weight estimation device.

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

PTN investigator to retire at end of 2017

 

In 2004, Dr. Ram Yogev, Director of the Section on Pediatric, Adolescent and Maternal HIV Infection at the Ann & Robert H. Lurie Children’s Hospital of Chicago, was invited to serve on an FDA advisory committee on anti-retroviral, anti-fungal and anti-tuberculosis drugs. As the only pediatrician on the committee, he was surprised to see that drugs were approved for pediatric usage with minimal supporting data and that information on optimal dosing for pediatric patients was virtually nonexistent.

The lesson stuck with him. In 2012, he became an investigator for the Pediatric Trials Network (PTN), conducting trials related to dosing of commonly used medications in children.

Dr. Ram Yogev (center) and Dr. William Muller (right) with Dr. Ellen Chadwick (left)

“The beauty of PTN research is that it gives us the basis for making better decisions in how we treat our patients,” he said.

For the past 5 years, Dr. Yogev has been an invaluable member of the PTN team. He was involved in several studies related to antibiotics, anti-epileptic drugs, and a measuring tape used to determine an infant’s weight when using a scale is impractical. He also enrolled the highest number of participants of any site in a 2012 trial assessing appropriate dosing for a variety of understudied drugs, and contributed more than 44,500 patient records to the PTN Data Repository, which will be used to inform the design of future PTN studies.

After more than 40 years as a practicing physician, Dr. Yogev is retiring at the end of this year. Taking over Dr. Yogev’s role with PTN will be Dr. William Muller, attending physician for pediatric infectious diseases at Lurie Children’s, who lists Dr. Yogev among his mentors.

Laying the foundation

Dr. Yogev has specialized in pediatric and maternal HIV since 1986, when he treated a young patient who had been infected with HIV during a blood transfusion. He found, to his dismay, that many physicians refused to treat HIV-positive patients.

“For me, it was obvious what I needed to do,” he said. “The essence of medicine is the humanity of it. Medicine is important, but more important to me is how the child and his or her family are coping with the disease socially and emotionally.”

In his quest to find innovative solutions for his most vulnerable patients, Dr. Yogev became a champion of clinical research. Named director of the Experimental Therapeutics Program of Children’s Memorial Research Center in 2005, he is credited with building the hospital’s clinical research program from the ground up.

“I had to develop an infrastructure to support my own studies,” Dr. Yogev said. “It quickly became obvious what the obstacles were, so I began to work to address them.” For example, after finding that transportation was a major challenge for people participating in trials, he acquired a van and a driver. He also hired his own phlebotomist to meet the research PK demands more efficiently and to keep from overburdening the hospital staff.

“Soon we were expanding the clinical research unit, educating physicians on clinical research, and developing a mechanism where people were recognized for their contributions and expertise,” he said. After about 5 years, the unit, now known as Clinical and Translational Research (CTR), was providing critical services to more than 125 physicians conducting clinical research at the hospital.

With funding from the NIH, Dr. Yogev also helped develop clinical research sub-units in Thailand and South Africa. Now independent sites, both are successfully conducting clinical trials on their own.

“There’s nothing more rewarding than seeing a sub-unit performing as well as the main site,” he said. “It’s like the pride a father feels when he sees his son or daughter is getting better than him.”

Taking the reins

Dr. William Muller, who will assume Dr. Yogev’s role of site investigator at the end of this year, has worked closely with Dr. Yogev since joining Lurie Children’s 10 years ago. They also both teach pediatric infectious diseases at Northwestern University’s Feinberg School of Medicine.

Dr. Muller’s area of study relates to the effects of viruses such as herpes simplex, Zika, and HIV on neurocognitive development. His current research explores how to most effectively prevent and treat herpes simplex encephalitis in newborns. He also researches infections in immune-compromised patients.

His ultimate goal is to make sure the results of clinical trials are communicated in the field, where they can be incorporated in decisions made when treating patients.

“You spend a lot of time in the lab trying to tease out why something happens, but that doesn’t necessarily help patients,” Dr. Muller said. “We have to look at how this can lead to better outcomes in the people we’re treating.”

Dr. Yogev credits Dr. Muller and the rest of the dedicated team at Lurie Children’s with his success. “They don’t mind what time of day or night; if something is needed, they are there,” he said. “I’ve truly been standing on the shoulders of giants.”

Nov. 17 marks World Prematurity Day

Friday, November 17th marks World Prematurity Day. Part of the March of Dimes’ Prematurity Campaign, the event is designed to raise awareness of the problem of premature birth and to support ongoing efforts to reduce rates of premature birth in the United States and around the world.

Rachel Greenberg, MD

According to the March of Dimes, roughly 10 percent of U.S. births each year are premature, meaning that they take place before the 37th week of pregnancy. The World Health Organization identifies complications resulting from premature birth as the leading cause of death for children under the age of 5, and premature infants have a substantially elevated risk for a host of serious medical problems, some of them lifelong.

“With premature babies, pretty much every organ system is immature – everything is still developing. The human body wants a chance to mature for 9 months, and when it doesn’t get that chance, there are challenges,” says Dr. Rachel Greenberg, a neonatologist at the Duke Department of Pediatrics and a researcher with the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pediatric Trials Network. She notes that these challenges are complicated by the fact that some therapies that are vital to sustaining premature infants can cause them additional harm. Worse, many medicines used to treat premature infants are not well-studied in this fragile population.

“We have to make an educated guess on what the dose is, based on the dose in adults,” says Greenberg, whose work with the Pediatric Trials Network is focused on gathering evidence to guide the use of medications in children and infants.

Premature birth also takes a heavy toll on parents, who often endure tremendous emotional stress while their child undergoes treatment—sometimes for weeks or months—in a hospital neonatal intensive care unit. “It can be the happiest day of their lives, and it can be the scariest,” notes Dr. Greenberg. “They’re so excited to have a child, but the baby’s sick.”

While neonatologists like Greenberg seek better treatments for premature infants, World Prematurity Day is part of efforts to prevent premature birth in the first place. This is a particularly urgent issue, as rates of premature birth have been rising around the globe in recent years, including in the United States, whose overall performance earns it a grade of “C” on the March of Dimes’ 2017 Premature Birth Report Card. Although infections and other underlying health issues in the mother are known to play a role, Duke’s Greenberg points out that the chain of events leading to a premature birth is often far from clear.

“Many times, we don’t know what causes it,” she says.

The March of Dimes’ Prematurity Campaign is supporting research into preventing premature birth, with the goal of reducing the U.S. rate of premature birth to 8.1 percent by 2020. The campaign also supports efforts to improve care delivery and foster advocacy and community engagement.

More information on World Prematurity Day activities, as well as ways to get involved, can be found at the March of Dimes website.

PTN determines appropriate TMP/SMX dosing in infants and children

Micky Cohen-Wolkowiez, MD, PhD
Micky Cohen-Wolkowiez, MD, PhD

The Pediatric Trials Network (PTN), with funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), recently completed a multicenter study of trimethoprim/sulfamethoxazole (TMP/SMX) to determine appropriate dosing for infants and children. The results of the study were published in the journal Antimicrobial Agents and Chemotherapy on Oct. 30.

TMP/SMX is a combination antibiotic used to treat various types of bacterial infections in children, including urinary tract infections, bacterial pneumonia, and skin abscesses caused by methicillin-resistant Staphylococcus aureus (MRSA). Although it is one of the most commonly used drugs for treating infections in infants and children, pharmacokinetic data in children are lacking and appropriate dosing information had never been determined for this population.

“It’s common to extrapolate adult doses to treat children,” said Dr. Michael (Micky) Cohen-Wolkowiez, co-principal investigator for the study. “However, developmental changes during childhood play a significant role in drug dosing, and failure to account for these changes often leads to decreased drug efficacy and safety in young patients.”

During the study, investigators analyzed samples from 153 infants and children who had been given TMP/SMX as part of their treatment. The TMP/SMX combination is one of more than 30 drug therapies given as part of standard care that are being evaluated in POPS, a study that began in 2011 and is expected to have enrolled approximately 3000 patients by 2018.

Only a small percentage of drugs and devices approved by the FDA are actually labeled for pediatric use. As a result, pediatricians must frequently prescribe medical therapies according to their best guess based on dosing information from adult studies.

PTN, a network of more than 100 sites in 5 countries, aims to fill this gap by conducting trials primarily with off-patent drugs that lack data to guide their use in pediatric populations. Since its inception in 2011, it has studied 72 drugs to determine appropriate dosing for children and infants.

PTN study contributes to successful treatment of MRSA abscess in preterm infant

Early this summer, Lucas,* a one-month-old infant born 9 weeks prematurely, was receiving routine respiratory support in the neonatal intensive care unit at the University of North Carolina Children’s Hospital when he suddenly developed a dangerous neck abscess. Upon testing, the infection was found to be caused by methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Staphylococcus infections in general can be life-threatening in the NICU, but because MRSA is resistant to many commonly used antibiotic therapies, Lucas’ treatment options were limited from the outset.

Dr. Jackie Patterson
Dr. Jackie Patterson, UNC Children’s Hospital

Neonatologist Jackie Patterson, who was caring for Lucas in the NICU, immediately turned to the medical literature to determine the best course of treatment. During her search, she found an article published in the May 2016 issue of Antimicrobial Agents and Chemotherapy that was directly relevant to Lucas’ case. The article reported results from a trial sponsored by the Pediatric Trials Network (PTN) that explored dosing for antibiotics including clindamycin in infants being treated for staph infections.

Clindamycin was originally approved by the FDA in 1997 and is used to treat bacterial infections when other antibiotics, including penicillin and methicillin, are ineffective. The PTN “Anti-Staph Trio” study, a multicenter trial that evaluated 3 different antibiotic therapies for staph infections, was designed to identify drug dosages appropriate for use in term and pre-term infants—information that was not available in existing product labeling.

By combining their findings with pharmacokinetic and safety data from two other studies, the authors were able to describe a dosing regimen for clindamycin in premature infants based on postmenstrual age and total body weight that would allow physicians to effectively treat the infection while avoiding unwanted side effects.

Dr. Patterson knew, based on lab results, that Lucas’ particular strain of MRSA was sensitive to clindamycin. Thanks to the data published in the PTN study, she was able to choose a dosing strategy that would be most effective for Lucas.

“After only a couple of days, we saw a dramatic improvement with no adverse effects,” she said. Lucas recovered completely by the end of the week-long treatment, and was discharged healthy later in the summer.

Although Lucas’s parents had initial concerns about the treatment, they were reassured when Dr. Patterson referenced the study.

“We were confident about our treatment because of the literature,” she said. “This made the family confident in us.”

However, Dr. Patterson noted that this is not always the case, pointing out that information to guide dosing for infants and premature neonates is often sorely lacking.

“In pediatrics, we’re often extrapolating from adult data,” Dr. Patterson said. “In part because families are reluctant to enroll their children in clinical trials, it’s hard to find data specifically related to infants and children.”

Bridging this gap is a key goal for the PTN, an alliance of more than 100 clinical research sites cooperating in the design and conduct of pediatric clinical trials. Sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the PTN works to improve healthcare for the youngest patients by providing much-needed information on optimal dosing of commonly used drugs.

“The work that PTN is doing is critical,” Dr. Patterson said. “Especially when working with life-threatening conditions in the newborn population, the more science behind our medical practices, the more confident we can be that we will deliver the best outcomes for our patients and their families.”

*Name has been changed to protect confidentiality.

DCRI and partners awarded FDA grant to create Global Pediatric Clinical Trials Network

The Duke Clinical Research Institute and its strategic partners have been awarded a grant from the U.S. Food and Drug Administration (FDA) to establish a coordinating center for a Global Pediatric Clinical Trials Network (G-PCTN). The G-PCTN will support efficient pediatric clinical trials worldwide by developing scientific and operational infrastructure, fostering collaborative networks, sharing knowledge, and engaging stakeholders. The principal investigators for this program will be Drs. Danny Benjamin and Michael (Micky) Cohen-Wolkowiez.

“Although we’ve made a lot of progress in recent years, pediatric trials are still hard to complete successfully. There are perennial challenges – enrolling patients, finding access to supporting infrastructure, navigating a complex regulatory environment – that affect everyone working to advance pediatric research, but they can be especially challenging for research sites that don’t have access to resources or experience,” said Benjamin. “We’ve had great success with the Exclusivity Program, and NICHD’s off-patent program; but we need to work through some of the challenges that folks have had in meeting the requirements outlined by the Pediatric Research Equity Act. It’s crucial to have success across new therapeutics for children.”

Although the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were both implemented to encourage research sponsors to conduct more pediatric clinical trials, many drugs used in children lack sufficient information to guide their safe and effective dosing. Further, 42% of pediatric trials done under BPCA have not successfully supported pediatric indications.

“Despite how vital it is for children’s health, proper dosing information is still sorely lacking for many important therapies used in children and infants,” Cohen-Wolkowiez said, noting that the relatively small numbers of patients eligible to enroll in pediatric trials of therapies for rare diseases adds an additional layer of difficulty. “This Network will provide a key opportunity to address inefficiencies and build capacity across the globe for conducting more effective pediatric clinical trials, which will help inform the decisions parents and healthcare providers make when caring for our youngest patients.”

The grant will be used to create a coordinating center comprising 3 cores for network operations, patient engagement, and scientific oversight and 5 clinical study groups devoted to study design, dosing, regulatory/pharmacy, network partnerships, and rare diseases. Benjamin, who also serves as Principal Investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pediatric Trials Network (PTN) envisions the programs working synergistically: “There are natural interactions, or lessons learned, across the trials conducted in the older, off-patent medicines and the trials conducted for newer therapeutics.”

The creation of the Network reflects consensus findings from a multistakeholder group that included regulators, industry, academia, patient advocacy groups, disease networks, and parents. The group noted that no one set of stakeholders can address these problems in isolation; instead, a global network involving all stakeholders could better ensure successful pediatric trials, especially those being conducted in patients with rare diseases.

The G-PCTN will leverage and extend the extensive infrastructure, networks, and experience already in place via the PTN, whose administrative coordinating center is also located at the DCRI.