Ped Med: Children as "Therapeutic Orphans"

By Lidia Wasowicz

San Francisco - Rarely wanted by treatment testers, often left to the vagaries of medical guesswork by the system charged with their care, U.S. pediatric patients have also come to be known by another name: "therapeutic orphans."

By most estimates, as many as seven of every 10 medicines doled out to minors do not carry the official seal of approval for that age group.
A formal nod from the federal Food and Drug Administration may not provide a guarantee of a remedy's safety and effectiveness, but at least it offers a measure of reassurance the drug has met some preset standard of scientific scrutiny relevant to the case at hand.

"About 75 percent of all drugs prescribed for children are not tested for use in children, and as a result they may be ineffective or even harmful," cautions the FDA, the agency established to keep dangerous pills, potions, powders and products out of public reach.

Rather, the chemicals are tried out in adults. Once authorized as a remedy for a particular ailment in grown-ups, the medicines become fair game for doctors to put to any "off-label" purpose in any patient they see fit. In contrast, the drugs' makers are forbidden by law to promote any unapproved use.

"It's rarely in a pediatric practice setting that the pediatrician is not prescribing some medication off-label for something," said Dr. Jeffrey Stoddard, a veteran pediatrician, vice president at Covance Inc., a drug development services company, and former senior director of medical affairs for influenza programs at MedImmune in Gaithersburg, Md.

The company, which makes the nasal FluMist vaccine, specializes in developing pharmaceuticals for childhood infectious disease.
A lack of federal sanction does not necessarily connote a lapse in scientific footing.

"For almost all drugs used in the pediatric population, some testing has been done to estimate the dose, efficacy, side effects, drug-drug interaction," said Dr. Cheston Berlin Jr., professor of pediatrics and pharmacology at Pennsylvania State Children's Hospital in Hershey, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine.
"For many compounds, there needs to be more (testing), particularly in the areas of pharmacokinetics (the way the body absorbs, distributes, metabolizes and excretes the medicine) and pharmacodynamics (the way the pharmaceutical affects tissues and organs)," added Berlin, the 2003 Pennsylvania Pediatrician of the Year and member of the American Academy of Pediatrics Committee on Drugs which developed ethics guidelines for conducting medical research in children.

In some instances, the drugs may be missing more of the financial than scientific backing needed to earn federal clearance. Until recently, among children's remedies, FDA approval was largely confined to antibiotics.
"Many treatments have good data but are not FDA-approved because of the expense of getting drug approval," said Donna Palumbo, associate professor of neurology and pediatrics and head of pediatric neuropsychology training at the University of Rochester School of Medicine and Dentistry in Rochester, N.Y.

Often, off-label drug use "may represent the only, or best, treatment available for a specific illness in a child," pediatricians testified before a congressional subcommittee looking into the practice.
Even so, it can be a crapshoot.
"You don't know if the child is safe if you don't have FDA approval," said Palumbo, principal investigator on a government-funded study of attention-deficit/hyperactivity disorder in preschoolers. "For a drug that has not been shown to be safe and effective in an FDA-approved trial, each child that comes through your door becomes an experiment."

In the absence of standardized labeling information to guide them, pediatric practitioners rely on published literature, word of mouth, extrapolation from adult findings and their own professional judgment and clinical experience to determine suitable dose and duration of treatment.
"Drugs are commonly used off-label without a good understanding of the proper dose or monitoring or what the side effects might be," said Dr. Jeff Blumer, professor of pediatrics and pharmacology at Case Western Reserve University, chief of the Division of Pediatric Pharmacology and Critical Care, professor of pediatrics and director of the Pediatric Intensive Care Unit at Rainbow Babies and Children's Hospital in Cleveland, Ohio.
"Some understanding comes from experience, but everyone's experience is different," added Blumer, member of the pediatrics academy's Committee on Drugs. "Generally, we take our best guess based on what's been done before."

Most often, doctors rely on previous clinical reports.
"The Committee on Drugs ... regularly publishes a series of statements on the treatment of certain conditions in (the journal) Pediatrics," Berlin said.
In addition, the National Institutes of Health has published reports on the treatment of asthma in children, while numerous societies and associations have prepared a variety of practice parameters to supplement the standard texts, he said.

Still, even with long-used, child-tested medicines and ailments as common as an ear infection, there remain divergent viewpoints on such basic questions as when to allow a condition to self-correct, when to treat it pharmaceutically and when to employ non-drug therapy.
"The current controversy about when to treat otitis media (ear infections, which some reports say are best left untreated) in children is a good example of this dilemma," Berlin said. "In the absence of ideal treatments, this usually means that there is not one that all can agree on."

(Note: This column is based on dozens of reports, studies and conferences and more than 200 interviews with specialists in children's health issues. Wasowicz is the author of the new book, "Suffer the Child: How the Healthcare System Is Failing Our Future," published by Capital Books.)