Congress set to reauthorize drug study laws next year

May 1, 2011

The nation has been struggling for many years to correct for the many years that medications were not studied in children.

The nation has been struggling for some time to correct for the many years that medications were not studied in children.

A 2007 Government Accountability Office report said that two-thirds of drugs prescribed for children had not been studied and labeled for pediatric use.

That same year, Congress reauthorized legislation requiring federal agencies to work to ameliorate the problem. Food and Drug Administration (FDA) officials say that since that time the proportion of unstudied drugs may have been reduced closer to 50%, although FDA currently has a project to update the list of drugs used in children.

According to FDA, more than 100 drugs have had some kind of studies done on them since that time. The majority (83) were required under the Pediatric Research Equity Act (PREA), which mandates a pediatric assessment of drugs and biologic products when the product's sponsor applies to FDA for a new active ingredient, indication, dosage form, dosing regimen, or route of administration.

Twenty-one drugs have been studied under the Best Pharmaceuticals for Children Act (BPCA), which, among other things, allows FDA to extend the patent life of drugs if the sponsor does pediatric studies, often a major financial incentive.

Twenty-six other drugs have been studied as a result of BPCA and PREA.

FDA official Robert Nelson, MD, PhD, says that progress has been dramatic, with more than 400 label changes, over the approximately 14 years that at least parts of the legislation have been in place.

A big problem continues to be finding the resources to have studies done on off-patent drugs, because drug manufacturers or sponsors have little incentive to do so.

The BPCA legislation does provide funds for the National Institutes of Health (NIH) to sponsor some pediatric studies on off-patent drugs; however, that public funding is not quite in the realm of what drug manufacturers spend on trials for drug approvals. That's a big reason there's been little progress in label changes for children for off-patent drugs, says Nelson, pediatric ethicist in FDA's Office of Pediatric Therapeutics. Many drugs used in children are off patent, he said.

Currently there are 14 clinical trials being sponsored by NIH under BPCA, according to Anne Zajicek, MD, PharmD, chief of the Obstetric and Pediatric Pharmacology Branch at the National Institute of Child Health and Human Development (NICHD). Most of them have finished recruiting and data will be submitted to FDA later this year.

The process can be more complicated than simply looking at effectiveness. Sometimes there is a need for a preliminary study to determine the correct dose, Zajicek said, and even some outcome measures have not been validated.

One important thing from the 2007 reauthorization, according to Zajicek, is funding for infrastructure for trials, something that has been lacking. The needs include remaking pediatric formulations for the purposes of the trials, finding people who know how to do clinical pharmacology trials, designing the trials, and analyzing the results.

To help meet that need, NIH has funded clinical pharmacology training programs at 7 universities, as well as other grantees funded under NICHD.

In addition, the NICHD last year awarded a contract to Duke University to create a Pediatric Trials Network so that structure will not have to be rebuilt each time. It will offer expert consultation, pediatric clinical pharmacology, product formulation, drug distribution, and device development.

One piece of advice Nelson has for his fellow pediatricians is to encourage parents to put children in clinical trials when it's appropriate because, "We don't know what we don't know."