The effects on children of pediatric drugs approved before 1998 were largely un-researched. However, that could change with a Duke-led study on drug doses for children, funded by $95 million from the National Institutes of Health.
In 1998, Congress passed laws authorizing the Food and Drug Administration to require prescription drugs used on children to be studied before they arrive on the market. As for drugs approved prior to then, there was no way to adequately study them and their effects on children. However, this seven-year initiative will attempt to answer questions on correct dosages and product safety and compare products to each other. Prior to 1998, doctors relied primarily on the educated guesses of experts to determine the correct dosages for their youngest patients.
But even those weren’t accurate enough, research has shown.
“Sometimes the [differences in dosages] are not too big, but sometimes they are ten-fold wrong or a twenty-fold dosing difference,” said Dr. Daniel Benjamin, a professor of pediatrics at Duke and faculty associate director of the Duke Clinical Research Institute, who will be leading the new project.
Additionally, Benjamin said the experts were wrong one-third of the time.
“In children, they have different ages at when they develop different enzymes in their liver that break down drugs,” Benjamin explained. “Their kidney function is different from adults in how fast they clear things. In some years they are more efficient; in some years, they are less efficient.”
As a result, the amount of a drug a child needs will vary. In addition, drugs can be shunted down various metabolic pathways in children, leading to extremely unpredictable outcomes, Benjamin said. Because of this, children cannot be treated as miniature adults and have their dosages scaled down accordingly.
Throughout the next seven years, the goal of the study will be to develop 14 different trials, said Katherine Berezny, Duke’s project leader for the trials.
Each trial will enroll between 100 and 200 children of both sexes and of varying ethnicities and ages. The studies will primarily focus on drugs for serious health problems and life-threatening conditions, where it would be critical to have the appropriate dose. Other selection factors include the extent to which the drug has been studied before and the feasibility of a study with a certain drug, Benjamin said.
It costs roughly $10,000 to $20,000 for every patient enrolled in these trials, he added. These thousands of children will need nurses to help facilitate data collection, including blood samples and vital signs. The blood samples nurses collect will be sent to a central lab and analyzed. The researchers need to validate the results and prove to the FDA that the same results are obtained every time. This validation process is complex and expensive. To account for all these costs, when the money comes to Duke, the researchers will need to ensure the funds get distributed evenly.
Berezny emphasized the importance of this project and noted that the money for the project represents “one of the largest amounts of money set aside for pediatric drug research.”
In an e-mail, Dr. Robert Harrington, director of the Duke Clinical Research Institute, expressed enthusiasm for the project as well, calling these studies “long overdue.”
“It’s astonishing that clinicians have been forced to try and prescribe therapies in children for which basic information regarding the relationship between dose and outcome, safety and efficacy, is so unclear,” he wrote. “Understanding the basic tenets of drug therapy is critically needed.”
Benjamin said these studies will have tangible results, noting the lack of formulations for medicines taken by two of his sons.
“When you think about formulations and pediatric drug developments, it hits a little closer to home than you might initially anticipate,” he said.
Get The Chronicle straight to your inbox
Signup for our weekly newsletter. Cancel at any time.