(Page 3 of 3)

"There was no infrastructure for the research before," says Floyd R. Sallee, M.D., Ph.D., a child psychiatrist and director of the pediatric pharmacology research unit at Cincinnati Children's Hospital Medical Center. "I see the culture changing in industry and at FDA," he says. "Drug companies have hired pediatric experts and there is a larger network of expertise to draw from."

Sallee's center is part of the Pediatric Pharmacology Research Unit (PPRU) Network, a group of centers that conduct pediatric drug trials with support from the National Institute of Child Health and Human Development (NICHD). The network was established in 1994 and now includes 13 PPRUs.

Shirley Murphy, M.D., (no relation to Dianne Murphy) joined the FDA in September 2002 as director of the Division of Pediatric Drug Development. She says linkages between the FDA, NICHD, AAP, and other organizations have been important for building a foundation for pediatric research, and children are getting more and better drugs as a result.

"What it means for parents is that they can feel more secure knowing that their children are being treated appropriately," Shirley Murphy says. "FDA remains committed to keeping pediatric drug research a high priority."

Several areas that will continue to receive the agency's attention include the ethics involved with studying drugs in children. The FDA's Pediatric Advisory Subcommittee has concluded that generally, pediatric studies should be conducted in subjects who may benefit from participation in the trial. Usually, this implies the subject has or is susceptible to the disease under study.

Debbie Birenbaum, M.D., an FDA pediatric team leader, says FDA experts think long and hard about the public health benefit before requesting pediatric studies. "We don't want to under study children and we don't want to over study them. It's our job to get information that will help them and protect them at the same time."

Shirley Murphy cites pediatric oncology as another important area for the agency. "The development of cancer drugs needs special consideration," she says. Differences in the biology of tumors in children and adults usually make it difficult to prescribe children drugs based on adult data. And it has been typical for new cancer drugs to reach children late — only after they have been tested in adults.

As a result of pediatric initiatives, there have been about 30 studies initiated on cancer drugs, which will help researchers gain access to potential new cancer therapies for children.

While it may be challenging to enroll children in clinical trials for some diseases, that's not the case with cancer. Most children receive their cancer therapy as part of a clinical trial. "Parents are desperate to have their children in these studies," says Patrick Reynolds, M.D., Ph.D., a pediatric oncologist with Childrens Hospital Los Angeles. "They know very well what the odds are and they want to take a chance to find life-saving treatment. They also want to help other children. They don't want to do nothing."

Reynolds is a member of the FDA's Pediatric Oncology Subcommittee, a group of outside experts who have met several times since 2000 to advise the agency on such questions as: In what phase of a drug development program should pediatric cancer studies begin? What trial designs should be used? How may data from adult studies be used in pediatric studies? How should adult and pediatric studies be coordinated when studying life-threatening diseases?

Reynolds calls both the pediatric rule and the exclusivity provision essential. "Children don't have a voice in this," he says. "Somebody has to stand up for them."

Changing Drug Labels

Recent pediatric drug studies have resulted in the addition of pediatric information to the labeling for more than 40 drugs. The drug labeling provides guidance for doctors and other health-care providers on how to use a drug. Here are examples of several changes that are considered significant for dosing and risk.

Luvox (fluvoxamine): Treats obsessive-compulsive disorder. The dose of the drug may need to be increased up to the recommended adult dose in adolescents, but may need to be prescribed in lower than recommended doses for girls ages 8 to 11.

Neurontin (gabapentin): Treats seizures. Safety and effectiveness have been established for children as young as 3. Children under 5 need higher doses than previously thought based on the studies conducted. New adverse effects not seen in adults, such as hostility and aggressive behavior, are now noted in the label.

Diprivan (propofol): An anesthesia drug. A research study showed an increase in deaths when the drug was used for pediatric ICU sedation in comparison with standard sedative agents. Administration of propofol with the pain medication fentanyl may result in serious slowing of the heart rate.

BuSpar (buspirone): Treats generalized anxiety disorder. Safety and effectiveness were not established in patients ages 6 to 17 at doses recommended for use in adults.

Versed (midazolam): Used as a sedative. The drug was shown to have a higher risk of serious life-threatening adverse events for children with congenital heart disease and pulmonary hypertension. Research identified the need to begin therapy with doses at the lower end of the dosing range to prevent respiratory problems in this special pediatric population.

Lodine (etodolac): Treats the signs and symptoms of juvenile rheumatoid arthritis. Research shows that the drug can be used in children ages 6 to 16 and that higher doses are needed in younger children.

Tags: Pediatrics

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.