Investigator Spotlight: Dr. Susan Rahman

Q: Could you tell us about yourself (background, areas of interest, expertise, etc.)?

A: I’ve been a pediatric researcher and innovator for nearly 30 years overseeing basic, clinical, and translational research programs. I’ve been funded by an array of sponsors (e.g. the National Institutes of Health, World Health Organization, Centers for Diseases Control and Prevention, National Endowment for the Arts) and have had the opportunity to conduct research in over a dozen countries across 4 continents. But no matter the location or sponsor, the focus of my research has always centered on improving the health of underserved and underrepresented populations.

Q:What PTN studies are you currently involved with? What are you hoping to learn from the study/studies?

A: I’m currently providing oversight for two studies as part of the PTN Diversity Metrics group. The first is a project examining the changes that get introduced to study protocols over their lifetime in hopes of understanding the extent to which patient burden is added or alleviated by sponsors and regulators. The second study is similarly themed and explores the extent to which investigators and participant families share perceptions of the burden carried by a study and its related protocol elements.

Q: Can you recall an especially impactful encounter with a participant and/or family of a participant?

A: As a clinician caring for the patients I engage in research, there are more poignant interactions than I can count. However, our recent implementation research has been particularly rewarding. We are developing solutions that empower parents and community health workers to improve the health and wellbeing of children in their homes and villages. Not only have we observed a measurable impact on child health, but we’ve heard directly from families about how meaningful these tools have been to them. It’s easy to forget that almost half of the world’s population doesn’t have access to basic health services so developing practical and sustainable solutions to address these gaps is incredibly satisfying.

Q: Why is the work of PTN important to you?

A: Any effort made to ensure the judicious use of medications in children should be lauded. However, what sets the PTN apart is their focus on medicines that might otherwise fail to receive the attention of researchers and their commitment to ensuring that the information garnered finds its way into the product label. It’s not just about conducting research and sending the results into the ether, but about working hard with regulatory colleagues to guarantee meaningful dissemination and application of the findings.

Q: What goals do you hope to achieve through your PTN-related work?

A: Through my current work with the PTN, I hope to remind pediatric researchers that the single most important partners we have are the patients, families, and communities we serve. They are an asset that we cannot undervalue, and we should strive to be purposeful in protecting this asset as we design and execute pediatric clinical trials.

Vance Fowler Jr.: PTN Principal Investigator at Duke University Medical Center

Dr. Vance Fowler ‘s interest in infectious disease blossomed in the highland rainforests of Tanzania, where he spent a year studying malaria during medical school as a Rotary Scholar. “What a blast,” recalls Fowler. “From plague outbreaks and river blindness to smallpox scars and rabid dog bites, this year was a crash course in infectious diseases. It also hooked me on clinical research, as I designed and completed my first clinical trial. Although the challenges then were a bit different— I had to learn Swahili to enroll study subjects, and excluded participants for simultaneously visiting their local traditional healer—the satisfaction of completing a clinical trial is still just as rewarding now as then.” Twenty years later, Dr. Fowler is a professor of infectious disease at the Duke University Medical Center, specializing in the treatment of patients with multi-drug resistant bacteria, and in particular methicillin-resistant Staphylococcus aureus (MRSA). As part of Pediatric Trials Network (PTN), he works to identify better ways to treat such multidrug-resistant bacterial infections in children.

MRSA is a “staph” germ that does not respond to the first-line antibiotics that usually cure staph infections. Most staph germs are spread by touch. Doctors, nurses, or hospital visitors may carry staph germs on their bodies that can be passed to susceptible patients. Once the staph germ enters the body, it can spread to bones, joints, the blood, or any organ, such as the lungs, heart, or brain, causing severe infection and even death. The consequences of S. aureus infections are particularly dire when they occur in newborns and premature infants.

The PTN is conducting a trial examining the pharmacokinetics of three drugs (rifampin, clindamycin, and ticarcillin-clavulanate) used to treat term and premature infants with staphylococcal infections, for which Dr. Fowler is playing an active advisory role. He is also advising the PTN on its forthcoming trial on the use of clindamycin to treat MRSA in overweight and obese children and adolescents. “Finding the right dose of these life-saving drugs to use in infants and children can make the difference between complete recovery and devastating neurodevelopmental impairment or death,” he observes. “The work of the PTN is filling a critical knowledge gap in infectious disease treatment.”

A native of North Carolina, Dr. Fowler also manages a family farm. Located on the banks of the Cape Fear River, the “River place” has been in Fowler’s family since 1737. In his off-hours, he enjoys spending time with his family, fishing, and running.

Kelli Brown: PTN Study Coordinator at the University of Louisville and Kosair Children’s Hospital

When asked about her research staff in the Kosair Charities Pediatric Clinical Research Unit at the University of Louisville and Kosair Children’s Hospital, Dr. Janice Sullivan is quick to recognize Kelli Brown, the primary coordinator for the POPS study at her site. “She is doing a tremendous job!” effuses Dr. Sullivan.

A research nurse coordinator for pediatric studies, Ms. Brown oversees everything from organizing the overall study and site initiation visit to screening patients for potential trial participation and helping to ensure that the trial protocol is followed to the letter. “She wears many hats in a given day,” notes Dr. Sullivan, “but Kelli never drops the ball and does it all with an easy smile.”

Ms. Brown’s professional interests run the gamut from the basic building blocks of life to the big picture. “Pediatrics and genetics intrigue me,” she explains. “DNA analysis and its potential for tailoring the treatment of disease are tremendous developments in medical practice.” On the other hand, she’s also very interested in exploring the benefits of holistic and alternative medicine for treating the whole person—body, mind, and spirit—as opposed to focusing only on his or her disease. “It’s hard to ignore the relevance of the mind and spirit to the healing process,” she observes.

Recently married last September, Ms. Brown and her husband enjoy hiking, biking, and traveling. In her alone time, she indulges in painting, cooking, and baking. Soon, however, her off hours will be filled with school work, as she has been accepted to the University of Louisville for an MSN program with a concentration in Family Nurse Practitioner.

Janice Sullivan: PTN Principal Investigator at the University of Louisville and Kosair Children’s Hospital

Dr. Janice Sullivan is a pediatric intensivist in the Kosair Charities Pediatric Clinical Research Unit at the University of Louisville and Kosair Children’s Hospital in Louisville, Kentucky, which means that she specializes in caring for infants, children, and adolescents with serious illnesses or injuries. She’s also a clinical pharmacologist with a focus on pediatrics and a particular interest in phase I trials (which test new drugs in small groups of healthy people to evaluate safety, determine dosage, and identify side effects). These varying passions drew her to the Pediatric Trials Network, for which she is serving as a PI on the POPS study and as a co-investigator with colleague Michael Smith, MD, on the study of clindamycin in overweight and obese children. Dr. Sullivan also acts as a member of the PTN Steering Committee, which oversees the network’s activities.

In recent years, her pharmacological and medical pursuits have merged in the advancing field of personalized medicine. Personalized medicine comprises an effort to tailor health care to each patient’s unique clinical, genetic, genomic, and environmental circumstances. Because these factors differ from person to person, the nature of diseases—from their onset and course to how they respond to drugs or other treatments—is as unique as the people who have them. Dr. Sullivan hopes to improve care for her young patients by taking into account as many of these factors as possible to ensure the best possible outcomes.

In addition to her clinical and research undertakings, she devotes a great deal of time to mentoring medical students, residents, and junior faculty, educating the next generation of physicians and scientists. Dr. Sullivan also chairs the Section of Clinical Pharmacology and Therapeutics for the American Academy of Pediatrics, which is currently working to address drug shortage issues that are dangerously compromising the care of children, particularly those who are critically ill.

Outside of work, she enjoys spending time with the latest addition to her family—her beautiful, 3-month-old “granddaughter” Ellie, who, according to Dr. Sullivan, “has won my heart.” Other hobbies include reading, quilting, home decorating, gardening, biking, and church activities. Awash in family and friends, she reflects, “I am so blessed!”

Adriana Tremoulet: PTN Principal Investigator at Rady Children’s Hospital, San Diego

Dr. Tremoulet is a pediatric infectious disease specialist who cares for children at Rady Children’s Hospital, San Diego. As part of the PTN, she is the site principal investigator responsible for the enrollment of study-eligible subjects into the POPS/PTN study of drugs used in children as a standard part of care.

Her research interests include pediatric pharmacology and the testing of new therapies for immunological and infectious diseases. Dr. Tremoulet is particularly interested in Kawasaki disease and serves as the associate director of the Kawasaki Disease Research Center at UCSD.

Kawasaki disease is a rare condition in children that involves inflammation of the blood vessels, which, in turn, can lead to aneurysms and heart attacks. In the United States, after congenital heart defects, Kawasaki disease is the leading cause of pediatric heart disease, with most patients aged less than 5 years. Dr. Tremoulet cares for nearly 1500 children with this devastating condition in San Diego County, as well as another 90 children hospitalized annually at Rady Children’s Hospital.

When she steps out of her white lab coat, Dr. Tremoulet enjoys dancing flamenco, an art form that she has practiced for over 15 years. She is also the proud mother of 2 girls and a 7-year-old chocolate Labrador retriever who is trained as a therapy dog.

Brenda Poindexter: PTN Principal Investigator at Riley Hospital for Children in Indianapolis

Brenda Poindexter is a clinical neonatologist, which means that she specializes in the care, development, and diseases of newborn infants (neonates), both premature and full-term. Working in a neonatal intensive care unit (NICU), she tackles issues related to premature birth, low birth weight, sepsis (infection) and septic shock, birth defects, critical illness, respiratory problems, and other life-threatening complications.

Her specialization in neonatal medicine makes her a valuable contributor to the Pediatric Trials Network, which seeks to fill gaps in knowledge about how best to treat these uniquely vulnerable patients. As the PTN principal investigator (PI) at Riley Hospital for Children, she oversees a staff of 7 research nurses, whom she describes as “hard-working, dedicated, and amazing women to work with.”

A professor of pediatrics at the Indiana University School of Medicine, Dr. Poindexter devotes her research efforts to the study of nutrition in premature neonates—specifically, the impact of early parenteral nutrition (intravenous feeding) on infant growth and neurodevelopment. She also investigates the effects of human breast milk on infant development. This work has been advanced through her involvement as a PI for the Neonatal Research Network of the National Institute of Child Health and Human Development, a role she has played since 2006 when she worked on a clinical trial studying parenteral glutamine supplementation in extremely low birth weight infants. She also serves as a PI for the multicenter Prematurity and Respiratory Outcomes Program (PROP) study funded by the National Institutes of Health.

In addition to these research activities, Dr. Poindexter coordinates all clinical research for the Division of Neonatal-Perinatal Medicine at Indiana University. She also serves as the vice chair for one of the biomedical institutional review boards at the university. (An institutional review board is a committee formally designated by an institution to approve, monitor, and review biomedical research involving humans that is conducted at the institution).

At home, the Poindexter women outnumber the man 5 to 1. Dr. Poindexter is the proud mother of 4 busy daughters: Emily (age 20, a pre-med student at Indiana University in Bloomington), Claire (age 17, a high school junior), Anne (age 14, a high school freshman), and Ellie (age 10, a 4th grader). The girls’ soccer and lacrosse games keep the family very busy. When college basketball season rolls around, the Poindexters will be rooting for the Hoosiers, who currently rank #1 in preseason polls.

Antonio Arrieta: PTN Principal Investigator at Children’s Hospital of Orange County

Director of Pediatric Infectious Diseases at Children’s Hospital of Orange County (CHOC), California, Dr. Antonio Arrieta is a board-certified pediatric infectious disease specialist who leads a team of 5 physicians providing inpatient and outpatient consults for the hospital and the community. He also directs the pediatric HIV treatment center.

Physicians trained in pediatric infectious disease treat a variety of infectious and immunologic afflictions, such as those caused by bacteria, viruses, fungi, and parasites. These specialists are also consulted regarding conditions that are complicated or atypical, including respiratory infections, bone and joint infections, tuberculosis, HIV/AIDS, hepatitis, and meningitis.

As a pediatric infectious disease specialist, Dr. Arrieta understands the unique symptoms, treatments, and outcomes associated with infectious diseases in children, which can differ quite radically from those of adults with the same conditions. He uses this knowledge to inform his research, which primarily addresses antifungal agents, pediatric HIV, and the safety, efficacy, and pharmacokinetics of medicines used to treat and prevent infectious diseases in children. Dr. Arrieta is a principal investigator for many studies being conducted at CHOC.

Although free time can be in short supply, when Dr. Arrieta has a spare moment, he enjoys playing squash, traveling, sampling various ethnic foods, visiting the local beach, and movie-watching. He also enjoys spending time with his beautiful wife and two children (ages 21 years and 15 years).

Joseph Flynn: PTN Principal Investigator at Seattle Children’s Hospital

Dr. Joseph Flynn is a professor of pediatrics and chief of the Division of Nephrology at Seattle Children’s Hospital. His personal vision for clinical research can be summarized quite simply: “For years, I have felt that every patient that we see should be viewed as a potential research subject. We’ll never advance our understanding of diseases and their treatment unless we enroll patients in clinical research.”

At Seattle Children’s, nephrology clinic nurses actively enroll patients in registry studies and provide them with preliminary information about clinical trials. Dr. Flynn feels that this type of clinical and research teamwork should be happening everywhere and is glad to be part of the Pediatric Trials Network, which is moving pediatric clinical research in that direction.

Dr. Flynn’s own research focuses on the epidemiology and treatment of childhood hypertension (high blood pressure), as well as the cardiovascular complications of pediatric chronic kidney disease. The study that Dr. Flynn is most enthusiastic about is a large observational cohort study called the Chronic Kidney Disease in Children (CKiD) study. Underway since 2003, CKiD is looking at risk factors for progression of chronic kidney disease (CKD) and the impact of CKD on growth, neurocognitive development, and risk factors for cardiovascular disease. Approximately 730 children are currently enrolled at around 50 centers across the United States and Canada, and investigators are getting ready to apply to the National Institutes of Health for a third five-year grant.

“The CKid study is very exciting,” says Flynn. “We’ve been extremely productive in terms of what we’ve learned about these children.” In addition to two papers currently in the works, key findings from CKiD that Dr. Flynn has helped to publish include the following:

  • Among children who are being followed at specialty centers for CKD, about 25% still have uncontrolled hypertension; even those who are being treated for hypertension still don’t have well-controlled blood pressure.
  • About 20% of children with CKD have a high rate of thickening of the heart muscle—left ventricular hypertrophy—which is related to abnormalities on 24-hour ambulatory blood pressure monitoring.
  • Many children with CKD have significant lipid abnormalities and other risk factors for heart disease.
  • There appears to be an impairment of IQ in children with CKD who also have elevated blood pressure.

Not only is the CKid study providing important insights that will inform future research, it has also resulted in direct, immediate benefit to some individual study participants. For example, Flynn reports that assessments included as part of the study have led to changes in medication or referrals to additional specialists.

Registries: Fighting the Stereotype

Although patient registries are “probably the least sexy kind of research,” Dr. Flynn believes they are extremely important, especially in less common pediatric conditions like kidney disease. Having a large number of research centers pool their data provides much more meaningful information than would the data from just one or two centers. Such registry data can be invaluable for generating new hypotheses and increasing understanding of these diseases. “There are certain questions you can’t answer any other way,” observes Flynn.

For example, Seattle Children’s was one of several centers to collaborate on the International Pediatric Peritoneal Dialysis Network. This group agreed to treat pediatric patients with peritonitis in the same way and then to pool their data to assess how well that treatment protocol worked. “Well, we learned that it wasn’t a good way…that the way we had been doing before was actually better,” says Flynn. This network now includes over 140 institutions, has over 1700 patients enrolled, and works to continue improving the care of children on chronic peritoneal dialysis.

Breaking New Ground with Clinical Trials

In addition to observational and registry studies, Dr. Flynn is also active in several clinical trials. In one current study, Dr. Flynn and his colleagues are looking at a new class of antihypertensive medication (recently approved for adults) that directly inhibits renin, an important hormone in blood pressure regulation. Another ongoing study is testing different dosing regimens for a medication used to treat anemia in patients with chronic kidney disease.

Seattle Children’s has just joined the Pediatric Trials Network as a participating site, and Dr. Flynn and his team are looking forward to helping the PTN make contributions to understudied areas in pediatrics, including pharmacokinetic studies of commonly used medications, and studies in underserved age groups, such as neonates. Dr. Flynn has been an advisor to the BPCA office of the NICHD since 2005 and is excited to see the growth of the PTN. He hopes to guide Seattle Children’s participation in many PTN-sponsored trials.

International Traveler

When Dr. Flynn isn’t working on his research, seeing patients at Children’s, or making trips to outreach clinics across the northwest region, he can often be found traveling the world. As president-elect of the American Society of Pediatric Nephrology and a member of the governing council of the International Pediatric Nephrology Association, Flynn is frequently asked to travel to far-flung locations for meetings and talks. Last year, he followed visits to Japan and Brazil with an invited speaking engagement in Dubrovnik, Croatia, a place he found “fascinating and beautiful.” Closer to home, he enjoys visiting the San Juan Islands and camping in the Cascade Mountains. Of course, he thinks the views of the Olympic Mountains and the Space Needle from his are office pretty great, too!

Debbie Gipson: PTN Principal Investigator at C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor

The adage that children should be seen but not heard does not ring true for Debbie Gipson. A pediatric nephrologist at the C.S. Mott Children’s Hospital of the University of Michigan, she has devoted her research career to investigating the health needs and outcomes of children suffering from diseases involving the kidneys. Fittingly, as high blood pressure can damage these organs, she serves as a member of the steering committee for the PTN hypertension trials.

Dr. Gipson’s research interests extend beyond diseases of the kidneys to the general conduct of pediatric clinical trials and the usefulness of patient-reported outcomes. “Patient-reported outcomes” are data reflecting self-reports from patients about how they feel following treatment. Because patients’ perspectives can play an important role in drug approval, this information can provide crucial insight about the relative success of a treatment. Integration of patient-reported outcomes into pediatric trial conduct helps to ensure that children have a voice in the clinical research process—an objective that Dr. Gipson believes to be very worthwhile.

As associate director for the University of Michigan Institute for Clinical and Health Research and member of the operations committee for the CTSA Child Health Oversight Committee, she is well positioned to keep children’s needs at the center of the research process. Notably, the NIH-sponsored Clinical and Translational Science Awards (CTSA) program encourages collaborative teams of investigators to tackle complex health and research challenges and find ways to turn their discoveries into practical solutions for patients. As such, it provides an exceptional vantage point from which Dr. Gipson can help to ensure that the national investment in health-related discovery includes children and their needs.

In her free time, Dr. Gipson enjoys hiking, kayaking, traveling, and spending time with family.

Howard Trachtman: PTN Principal Investigator at New York University Langone Medical Center

As a pediatric nephrologist, Howard Trachtman treats children with a wide range of kidney problems, from acute kidney disease to chronic kidney failure. The kidneys play a critical role in the body by acting as a filtering system, controlling water levels and eliminating wastes through urine. They also help regulate blood pressure, red blood cell production, and levels of calcium and minerals. The annual rate of kidney disease is only 1 or 2 new cases in every 100,000 children ages 19 and under. In the past two decades, however, the incidence of chronic kidney disease in children has steadily increased, especially among ethnic minorities and the poor.

Dr. Trachtman is particularly interested in glomerular diseases (i.e., diseases that affect kidney function by attacking the glomeruli—the tiny units inside the kidney where blood is cleaned), hemolytic uremic syndrome (a disorder that can occur when an infection in the digestive system produces toxic substances that destroy red blood cells), and hypertension (also known as high blood pressure).

In the Pediatric Trials Network, he acts as the lead investigator for trials concerning the treatment of hypertension. The first of these trials focuses on hypertension in child recipients of kidney transplants—the Safety and Pharmacokinetics of Lisinopril in Pediatric kidney Transplant Recipients trial. Lisinopril is approved by the U.S. Food and Drug Administration for use in children ages 6 years and older and adults with hypertension, heart failure, and heart attack. However, the appropriate dose of lisinopril in children below the age of 6 is not well known, nor is it known what dose should be given to children and adolescents who have received a kidney transplant and in whom hypertension is common. Because the drug likely behaves differently in these groups than it does in older children and adults, the lisinopril trial will meet an unmet public health need.

In his down time, Dr. Trachtman enjoys creative writing, as well as writing about bioethical issues inherent to research, often drawing on his knowledge of Jewish philosophy to inform his views. When he puts down his pen, he may be found running, playing with his grandchildren, or rooting for the Philadelphia professional sports teams. Dr. Trachtman also calls himself a very, very amateur piano player (“I think amateur overstates the case”).