New Law Mandates More Testing of Drug Safety in Children

[Guest guest]

New Law Mandates More Testing of Drug Safety in Children

http://www.medscape.com/viewarticle/465999?mpid=22483

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

Gorman, MD, a pediatrician in private practice in Ellicott City,

land. " 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 treat child 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. "