Parents assume that when a pediatrician prescribes a drug for their child, that drug has been tested and proven safe and effective. If only it were so. Only half of the medicines doctors prescribe to patients 18 and younger have been through the same rigorous trials as those drugs prescribed to adults. The other half are given off-label—that is, in circumstances for which they were never properly vetted, putting children at risk for overdoses, side effects and long-term health problems. For newborns, that fraction rises to 90 percent. In July the U.S. Congress gave the Food and Drug Administration new authority to compel companies to test their products for kids. The law should improve the situation, but it has worrying gaps.

As biologists have come to appreciate, drug metabolism is one of the many ways in which kids are not just small adults. When doctors downsize an adult dosage to suit a child's weight or body surface area, a drug can prove ineffective or harmful. Infants have immature livers and kidneys, so even a seemingly small dose of medicine can build up quickly in their bodies. As children mature, their organs can develop faster than their body size, so they need to take disproportionately more of the drug. For example, some recent pediatric clinical trials have found that the asthma medication albuterol does not work for children younger than four when taken through an inhaler. The seizure drug gabapentin (Neurontin) requires higher-than-expected doses for children under five.

The reason that drug companies neglect their youngest customers is simple. Children make up a small fraction of the world's drug recipients, so developing and testing new medicines for them is rarely worthwhile from a business perspective. Pediatric trials are especially expensive and complex, in part because of the difficulty of finding enough patients to enroll in them.

Congress began to address the issue in 1997, and its latest legislation, known as the FDA Safety and Innovation Act, strengthens those earlier efforts. The law requires pediatric studies for certain drugs and provides incentives to test others, such as a six-month patent extension. In addition, the law requires better advance planning of pediatric studies, improves the transparency of data and makes special provisions for newborns. The American Academy of Pediatrics praised the law: “The bill ensures that children will have a permanent seat at the table for drug research and development.”

Still, the law leaves many children vulnerable. It does little for youngsters with cancer, who rely disproportionately on undocumented drugs. Earlier this year Genentech won FDA approval for the skin cancer drug vismodegib, which intervenes in the same molecular process thought to be involved in a childhood brain tumor, yet the company was under no obligation to test the drug in younger patients. Congress needs to close this loophole, and in the meantime the FDA should continue to work closely with pharmaceutical companies and pediatric oncologists to find new ways of identifying and testing promising cancer medicines in children.

Another problem is that doctors are worryingly in the dark about the long-term health effects of pediatric drugs. Young people take medications for asthma, diabetes, arthritis and many other chronic conditions, yet rarely are side effects recorded and followed up on. In its February report “Safe and Effective Medicines for Children,” the Institute of Medicine recommended that the FDA make greater use of its authority to require long-term safety studies when it approves a product for pediatric use.

That said, the FDA Safety and Innovation Act is an important achievement. Children's medications are safer now than at any time in history, and many doctors and children's health advocates are so elated by the act's passage that they are reluctant to talk about what still needs to be done. But now is not the time to let up on our drive to make drugs safe for all our citizens. We hope this legislative victory will breed even more success.

8 Comments

1. 1. SteveCurry 02:40 PM 8/16/12

   I once heard a somewhat less charitable explanation for the lack of drug safety and effectiveness testing in children. It is hearsay and it may not be true. I would be interested if anyone can confirm or deny it. I heard that the six month extension of patent rights beyond the normal termination date is available for drug companies that need the time to complete safety and effectiveness testing in children. Consequently, it would be to the company's financial advantage to postpone that testing until the patent is about to run out in order to qualify for the extension. This would be a powerful motivation for a drug company to *delay* testing in children for as long as possible.

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2. 2. CalifBillR 01:56 PM 8/17/12

   This article contradicts a later article about 'Can We Keep Getting Smarter'. In fact, it suggests we are getting dumber. In only one place does this article actually mention in passing the real problem: "...in part because of the difficulty of finding enough patients to enroll in them". Do the authors actually imagine that any parent would willingly enroll their child/baby in an experimental drug program??? In the latest legislation requiring pediatric studies for certain drugs (for children), the FDA Safety and Innovation Act, exactly how are they going to force parents to allow drugs to be tested on their children? Will they fine them $2000/year if they don't comply as per the current government medical insurance plan? The comment above from SteveCurry shows how well the public has been trained to give a knee-jerk response to these issues - it's always the drug companies greed. In fact, I'm sure most drug companies would willingly test the drugs on children given the parents permission. Would SteveCurry or the authors of this article allow their children to be used in these trials? I highly doubt it. It is clear that information is needed in dosing children but this kind of nonsense reporting doesn't address the problem. I would very much like to hear from the authors how they plan to have children enrolled in these studies!!

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3. 3. voxfuror 03:52 PM 9/14/12

   It is always illegal to prescribe any medication for off-label use under Medicaid funded service delivery but that has certainly stopped very few doctors or organizations from doing so. Until there is a much higher level of accountability and culpability for these crimes against citizens there is little incentive to stop them and much to gain from these practices.

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4. 4. Charlie Taylor PhD in reply to SteveCurry 06:49 PM 9/14/12

   The truth is that drug trials are not safe in the early stages, and it is generally thought that conducting all the early safety and also efficacy/safety trials is more ethical in adults who can give informed consent than in children.
   
   There are no "evil thoughts" from the drug companies to delay testing in children...it's just that they don't want to expose kids to experimental medicines before they know they are relatively safe in adults. In some cases, it may not be ethical to do trials in kids, and specialized pediatricians have been doing great medicine for dozens of years using meds that were never approved for children.

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5. 5. kaebomb 12:00 PM 9/19/12

   I'm the parent of a 10-year-old child who was prescribed Ritalin. More than one doctor told him that his reported side effects were "all in his head" because they weren't on the list of side effects. When he stopped taking it however, his "imaginary" side effects went away. The carelessness in the medical field extends way beyond the drug companies...

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6. 6. tmorr01 in reply to voxfuror 10:19 PM 10/13/12

   It is not illegal to prescibe drugs for off label use under Medicaid guidelines. Medicaid does not presume to dictate medical care. It may be illegal to try to collect reimbursement for off label treatment. However, without reimbursement, where is the incentive for all these "gains". Actually, the incentive is successfully treating a patient with a drug that has a positive effect. An illegal act under Medicaid guidelines and a criminal act against the public are two different issues and are covered under different bodies of law.

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7. 7. tmorr01 in reply to kaebomb 10:27 PM 10/13/12

   If you had volunteered your son for the clinical trials for Ritalin, his "side effects" would have been included on the list. Would you have been willing to do so? Herein lies the major defect, as mentioned above, of the whole idea of clinical trials in children.

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8. 8. Generalwutangcharleschang 08:57 PM 3/1/13

   I'm flabbergasted by the innocuous attitude of pharmaceutical companies who should be doing more to improve safe drugs for kids, and human beings in general rather than screwing America's young-ins with doctored excuses. I understand from a research lab p.o.v. that there are certain "unique" challenges when conducting pediatric trials, re: complexity and cost, adding on the plausible disadvantage or "difficulty of finding enough patients to enroll...". However, we are talking about a gazillion-ba-billion-ten X a million and forty million pennies-industry (here). Spend the money on improving and making safer pediatric drugs; stop using economic justifications to overshadow morally reprehensible attitudes toward the priority level status of children. So what is the plan? We screw up them up before they even hit the ground as fully functioning human adults then we prescribe more shoddy, crappy, 1,000+1 side-effected drugs to keep the money wheel rolling. Orwellian epic here.

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