New Law Mandates More Testing of Drug Safety in Children

Cathy Tokarski

December 15, 2003

Dec. 15, 2003 — Lost in the front-page headlines earlier this month about creation of a new drug benefit for the Medicare population was passage of a law that advocates say will enhance the quality and safety of drugs that are prescribed for use in children.

The Pediatric Research Equity Act of 2003, signed into law by President Bush on Dec. 3, requires pharmaceutical companies seeking approval from the U. S. Food and Drug Administration (FDA) for their new drugs and biological products to assess a drug's safety and effectiveness, including dosages, in pediatric patients. Companies could be granted partial waivers from such assessments if such studies are "highly impractical or impossible" or if there is "no meaningful therapeutic advantage" in the pediatric population or is not likely to be used in a substantial number of patients.

In addition, according to the law, the federal government could require that labels indicate cases in which a waiver has been granted based on evidence that the drug would be unsafe or ineffective in treating children. The label can also specify a date by which an assessment should be submitted if the drug would provide a "meaningful therapeutic benefit" for one or more claimed indications and if it is used for a number of patients for the labeled indications and the absence of labeling could pose risk to the patients.

The law replaces the Pediatric Rule, a regulation that took effect in 1998 granting the FDA the authority to require pediatric drug studies. It was struck down in October 2002 by the U.S. District Court for the District of Columbia on the grounds that the agency did not have the statutory authority to require such studies.

Enactment of the Pediatric Research Equity Act into law is more than a procedural victory, according to physicians. Supported by the American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry, "it says [to drug manufacturers] right from the get-go, 'You need to put safety and efficacy data in as part of the development' when you're submitting a new drug application," said Adelaide Robb, MD, a child and adolescent psychiatrist at Children's National Medical Center in Washington, D.C. As a result, she added, physicians may be "more likely to look at newer medicines rather than only existing ones because they've only been tested in adults."

The law "is in place of doctors doing unregulated experiments," said Richard Gorman, MD, a pediatrician in private practice in Ellicott City, Maryland. "The reality is that children are not adults — they are physiologically different. Testing drugs in immature biological systems has taught us a lot," he added. For example, a pharmacology committee conducting clinical trials on a pediatric population were surprised to learn that dosing ranges for children were off by a factor of 50% to two times the appropriate amount, Dr. Gorman said. "It came as a huge surprise...we were giving either half of an appropriate dosage to two times as much."

Not everyone is enthusiastic about the FDA's new legal authority to require evidence of drug safety for children.

Vera Hassner Sharav, who heads the Alliance for Human Research Protection, a New York–based advocacy group, said children enrolled in clinical trials do not receive the protection they need and parents often are not adequately informed of potential downsides. "When children are recruited for studies that are not for a life-threatening condition, there is greater need to justify exposing children to pain risk and discomfort," she said.

Since the 1997 law creating the Best Pharmaceuticals for Children Act, which provided financial incentives for conducting pediatric studies, "children are being harmed," Ms. Sharav said. "The big one you have is SSRIs [selective serotonin reuptake inhibitors]," she said.

The use of antidepressants to treatchild and adolescent depression is "raising lots of controversy," said Dr. Robb, noting that the FDA will convene a meeting on Feb. 2 examining the link between suicide and use of various antidepressants by pediatric patients. But more, not less, research on drugs is needed to help physicians learn which medications work best in children, she said. "Even if all [SSRIs] work in grown-ups, we learned [from previous studies] they don't all work in kids. That helped us as pediatric psychiatrists determine which group of medicines to work from. That was an important finding."

Reviewed by Gary D. Vogin, MD

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