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.
“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.”