Drug Testing in Children

by Food and Drug Administration (FDA)

Q. Dr. Botstein, the FDA has been focusing more attention recently on drugs for children. Why is that?

A. There's a simple answer to your question: Pediatricians are infiltrating the FDA.

Q. (Laughing) Perhaps. But what's the real reason?

A. It's that children need medicines. Some drugs have already been well studied and approved for use in adults. To use one of these drugs for the same disease in children, it's important to figure out what doses work best in kids and what kinds of adverse reactions are likely to occur.

Other drugs are for diseases specific to children, and these need adequate and well-controlled studies of their effectiveness and safety.

Q. Can you tell me about the current situation? Are there lots of drugs approved for adults that are perhaps not well understood or well labeled for use in children?

A. The majority of drugs have been studied in adults and labeled for use in adults. Their physician labeling includes a disclaimer that says safety and effectiveness have not been established for use in children. That's the usual and common situation.

Q. So it's much more often the case that drugs have not been studied in children?

A. That's right. Even a drug like morphine, which is a standard, necessary pain medicine, has not had explicit labeling for use in children.

Q. Why haven't these drugs been studied in children?

A. In 1963, Dr. Harry Shirkey coined the phrase "therapeutic orphans" to describe children. Shirkey was alluding to the plight of children for whom many drugs have not been studied. The reasons for this are complicated. Pharmaceutical firms have had little incentive to study drugs for use in children because the population — and therefore the financial return — is likely to be small. Moreover, testing drugs in children is more complicated than in adults. Pediatric drug trials are often done in children's hospitals and may be more involved because people take pains to make sure that parents and children understand what's going on. Children are less likely than adults to be used as "normal" volunteers in clinical trials; most children in trials have the disease in question.

People are more reluctant to use a drug in children if there is no potential benefit to the specific child.

Q. But is this really a problem? Why can't physicians simply give a child less of a particular drug than would be given an adult?

A. It's not that simple. Young children may metabolize or absorb drugs at a different rate from adults, and therefore a suitable dose is difficult to estimate from the size of the children. The same is true for older adults, compared to younger adults. In recent years, FDA has paid more attention to establishing specific dosages for elderly patients, and we are now doing the same for children.

Q. So how do pediatricians know the proper dose of a drug if it is not specifically labeled for use in children?

A. That question goes to the heart of why FDA is encouraging clinical trials in children.

The answer is that there is no standard source of information. Pediatrics textbooks usually give drug dosages, but the source and reliability of the information are seldom specified. Mostly, pediatric doses of drugs that have not been formally studied in children are simply established by experience. Some drugs are used all the time in children. Anesthesia drugs would be a good example. They may not be labeled or approved specifically for children, but children routinely need major surgery. So physicians build up the experience in using the drugs. It's not the ideal way.

Q. You've established that many drugs currently approved for use in adults are not specifically labeled for use in children. But you mentioned a second category of drugs — new drugs specifically for childhood diseases.

A. Children have various types of diseases, the most common kind being acute infectious diseases — for which they need antibiotics, anti-fungal agents, and anti-viral agents. Some antibiotics are in fact studied and labeled for use in children — for meningitis or otitis media [middle ear infection], for example — while they are being studied for adults. But other major antibiotics, such as piperacillin or metronidazole, have no labeling for use in children.

Q. What are some other types of pediatric diseases for which adequate testing of drugs in children might be an issue?

A. In addition to the acute diseases, there are the chronic diseases of childhood, such as seizure disorders. Children also can have congenital diseases, such as cystic fibrosis and enzyme deficiencies.

Q. Are the drugs on the market without labeling for pediatric indications being used illegally?

A. No, doctors may legally use approved drugs for whatever uses they think appropriate, according to their medical judgment.

Q. As a pediatrician, you must be concerned. What sort of things is FDA doing to make more drugs available for children?

A. We're doing a number of things to be active in this area and are about to launch a plan for more. As we meet with drug companies to discuss the drugs they are studying, we are encouraging them to test those drugs in children when appropriate. We are finding that companies are often responsive to the need.

We are changing our internal procedures to foster the availability of new drugs for youngsters. We routinely ask our FDA drug review divisions to sift through their INDs [the formal requests to test a new drug] to identify drugs that might show particular promise in children. It is these drugs with potential pediatric uses that we encourage drug companies to develop for children, either before or after approval for use in adults.

We have created what we call a "pediatric page" as part of our review of new drug applications. This is a summary of what is known about the drug from the perspective of pediatrics: whether it has been tested in children, what uses are promising, and the like. It's basically a management tool, so that FDA's own people will think more in terms of drugs for children — and to explore this potential with the drug sponsors.

We are going to ask sponsors to tell us early in a drug's development about expected use in children and plans for studying the drug in children. We are also going to focus on actual use in children after marketing.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.