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.

POPS Paradigm Explained

PTN studies managed via the POPS paradigm seek to determine the appropriate dosing of understudied drugs in children by using samples collected as part of regular care (for example, blood draws). The data collected provides valuable pharmacokinetic and dosing information for drugs in different pediatric age groups and special pediatric populations (such as obese children).

Dr. Ram Yogev, POPS Investigator at Lurie Children’s Hospital of Chicago, explains, “The current empirically-based dose selection for pediatric patients can be improved by applying evidence-based dosing strategies. POPS studies provide important information about how best to dose medications in children and adolescents, and support dosing strategies that provide the best chance for any given drug to demonstrate both efficacy and acceptable tolerability.”

Since its inception, POPS has investigated 48 understudied drugs with 19 currently enrolling. POPS has a total of 31 active sites, and in March, two UK sites joined the ranks, Southampton General Hospital and Alder Hey Children’s Hospital. As of June 1, POPS sites enrolled 1904 participants of the targeted 3000.

SCAMP Enrollment is Wrapping Up

Two years ago, the study site at the University of Florida–Jacksonville Shands Medical Centerwe enrolled SCAMP’s first patient. With remarkable effort from more than 50 study sites, including 5 in Canada, SCAMP will close enrollment by the end of 2016. Once the enrollment period ends, the study team will analyze the data and submit the clinical study report.

PTN MD, Micky Cohen-Wolkowiez, receives Young Investigator Award

MCW_HeadshotMichael (Micky) Cohen-Wolkowiez, MD, PhD, director of the Duke Clinical Research Unit, has received the 2016 Young Investigator Award from the Pediatric Infectious Diseases Society (PIDS). The award recognizes a young physician whose research has generated outstanding contributions in the field of pediatric infectious diseases.Cohen-Wolkowiez is the author of more than 75 peer-reviewed publications and has led several multicenter pediatric studies, including trials for pediatric labeling. He also spent two years as a scientific advisor to the Office of Pediatric Therapeutics at the U.S. Food and Drug Administration and participated in a series of projects related to pediatric dosing and the ethical aspects of pediatric regulatory submissions.

“This prestigious award could have not gone to a more deserving physician-scientist,” says Coleen Cunningham, MD, professor of pediatrics and chair of the Divisions of Infectious Diseases and Global Health in the Duke Department of Pediatrics.

Cohen-Wolkowiecz received his medical degree from the Central University of Venezuela in 2001. He trained in pediatrics at the Miami Children’s Hospital in Florida and completed a pediatric infectious diseases fellowship at Duke University Medical Center in 2009.

PIDS is the world’s largest organization of professionals dedicated to the treatment, control and eradication of infectious diseases affecting children. Membership is composed of physicians, doctoral scientists, and others who have trained or are in training in infectious diseases or its related disciplines, and who are identified with the field of pediatric infectious diseases through clinical practice, research, teaching, and administrative activities.

PTN mentioned by Huffington Post blogger who offers global and longitudinal view of pediatrics research.

Over the past few decades, children’s health has arguably made some of the greatest gains. Infant mortality in most developed countries has fallen dramatically from an estimated 30 per cent to less than one per cent. Infectious diseases, the primary cause of infant mortality, have been addressed with better sanitation and water quality, and the development of vaccines and innovative new therapies. Parents need only consider penicillin or vaccines for polio, whooping cough, meningitis, and chicken pox to get a sense of the stress that parents would have had just a few decades ago.

Read the entire  blog post here.

PTN lisinopril study and subsequent label change highlighted in DCRI News.

Pediatric Trials Network study results in label change for hypertension drug

May 11, 2016 – The change could affect the hundreds of children who are prescribed lisinopril after kidney transplants each year.

A study conducted by the Pediatric Trials Network (PTN) has resulted in a labelling change for a widely used drug.

Lisinopril is an angiotensin converting enzyme inhibitor that is commonly prescribed to treat high blood pressure or heart failure in adults. It is also given to children who have hypertension, including children who have undergone kidney transplants. As with many other drugs, however, there has been little research to suggest the optimal dose for pediatric transplant patients. The PTN was established to answer these types of questions about drugs given to children and adolescents.

“There is a great medical need but a small market for these types of studies,” said Daniel Benjamin, Jr., MD, MPH, PhD, the PTN’s principal investigator (pictured). “This is why the PTN was formed—to conduct the studies that no one else will.”

A study led by DCRI researcher Uptal Patel, MD, and other researchers for the PTN recently resulted in a decision by the the U.S. Food and Drug Administration (FDA) to update the label for lisinopril. In addition to Patel, the study’s authors included Howard Trachtman, MD, of New York University; Adam Frymoyer, MD, of Stanford University; Laurence Greenbaum, MD, PhD, of Emory University; Daniel Feig, MD, PhD, of the University of Alabama at Birmingham; Debbie Gipson, MD, of the University of Michigan; Bradley Warady, MD, of Children’s Mercy Hospital of Kansas City; Jens Goebel, MD, of Cincinnati Children’s Hospital; and George Schartz, MD, of the University of Rochester.

The study was a multicenter, open-label pharmacokinetic study of daily oral lisinopril in 22 children, aged 7–17 years, with stable kidney function following transplant.

The researchers found that the pharmacokinetics of lisinopril in children who underwent kidney transplant were similar to hypertensive children who did not receive kidney transplants. Lisinopril was generally well tolerated by the patients and was accompanied by a lowering of blood pressure at approved pediatric doses in the study population.

The results of the study were published in the July 2015 issue of Clinical Pharmacology & Therapeutics.

Approximately 1,200 children in the United States develop end-stage renal disease (ESRD) each year. Because kidney transplantation has become the primary method of treating ESRD for children, many of these patients will be prescribed lisinopril. As a result of the FDA’s recent decision, Benjamin noted, doctors will now have a better understanding of the correct dose.

“This has been a problem for over 60 years, and we’re only now addressing it,” he said. “With the PTN, we now a have a vehicle to make those changes.”

PTN Gears up to Present at the 2016 Pediatric Academic Society (PAS) Meeting

PTN Investigators to present abstracts at the PAS Meeting in Baltimore, April 30-May 3

Here’s a sampling of presentations with more to come:

  • Platform Presentation: Sunday, May 1 at 4:15 PM–Dosing of antimicrobials in the neonatal in the NICU: Does clinical practice reflect published recommendations? M England, RG Greenberg, RH Clark, M Laughon, M Cohen-Wolkowiez, DK Benjamin Jr, and PB Smith on behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act – Pediatric Trials Network.
  • Platform Presentation: Saturday, April 30, 2016 at 8:00 AM–Use of Pediatric and Adult Midazolam Population Pharmacokinetics to Assess IM Dosing and Early Drug Exposure for Status EpilepticusE Capparelli, K Chiswell, B Smith, D Siegel, S Weinstein, S Muchohi,  M Reed, J Barrett,  S de Wildt, E Jaqc-Aigrain, J Ma, T Glauser for the Pediatric Trials Network.
  • Poster Presentation: Tuesday, May 3 at 7:30 AM — Using Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin Safety in Infants. S Salerno, C Hornik, M Cohen-Wolkowiez, PB Smith, R Clark, and D Gonzalez on behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act – Pediatric Trials Network.

NICHD Announces Research Funding Opportunity (U54)

Specialized Centers in Research in Pediatric Developmental Pharmacology (U54) 

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) announces the re-competition of the Research in Pediatric Developmental Pharmacology Centers Program (RPDP). 

The NICHD proposes to fund a limited number of research Centers that will provide an arena for multidisciplinary interactions between basic and clinical scientists interested in establishing high-quality translational research programs in the area of pediatric developmental pharmacology. The Centers also will serve as a national resource for the education of new scientists electing to pursue careers in the conduct of translational research in high priority areas of pediatric developmental pharmacology. Finally, Center investigators will facilitate important community outreach and education efforts to increase awareness and convey the importance and implications of their research activities to the general public.

Application deadline: February 18, 2016