Medication and Kids: A Growth Industry

Children have become the new growth industry for prescription drug makers. A study released last month by the pharmacy benefit manager Medco found that 26% of kids under 19—almost 30% of those aged 10 to 19—are now taking prescription medications for a chronic condition. Meanwhile, spending on prescription drugs for children increased by almost 11% last year, the largest increase experienced by all segments of the market, including the elderly. Although asthma drugs are the still the most commonly prescribed therapeutics, kids are increasingly being prescribed drugs that are decidedly uncommon for such young patients: atypical anti-psychotics, diabetes drugs, anti-hypertensives, cholesterol medications and heartburn drugs—expensive therapeutics that in the past were rarely used outside of adult populations.

The Medco figures are alarming first of all because intuitively it just feels wrong that so many children are downing prescription pills along with their morning multivitamin and orange juice. Kids are supposed to be healthy, full of energy, free spirited. But increasingly, this is not the case. More than 17% of adolescents (10-19 year olds) are now classified as obese: in fact, a whopping one out of three kids is considered overweight or obese. And obesity brings with it a raft of formerly adult chronic conditions.  According to a fact sheet provided by the Institute of Medicine, in one population-based sample some 60% of obese children aged 5 to 10 years had at least one cardiovascular disease risk factor—including high levels of total cholesterol, triglycerides, insulin, or high blood pressure—and 25 percent had two or more of these risk factors.

According to the Medco report, the incidence of Type 2 diabetes increased over 150% in kids between 2001 and 2009. Meanwhile, the industry newsletter The Pharmaletter reports that  “Type 2 diabetes medicines use by juveniles increased 5.3% in 2009, the largest increase across all age groups, and higher than overall utilization growth of 2.3%. Since 2001, the number of children aged 19 and younger using these medications has risen more than 150%, with girls between 10 and 19 showing the greatest jump at nearly 200%."

The news gets worse. A CVS Caremark study published in the April 2009 issue of Archives of Pediatrics and Adolescent Medicine, found that “over a two-and-a-half year period ending in June 2007, the use of medications to treat high blood pressure, high cholesterol and diabetes among children increased 15.2%.”  More evidence of a problem: The number of children regularly taking proton pump inhibitors, used to treat heartburn and GERD (also associated with obesity), and in some cases prescribed for colic in infants, increased by 147% from 2001 to 2009.

The carefree view of childhood takes a bigger hit if you look at the Medco findings on mental health. The study shows an increase in prescriptions for ADHD drugs like Adderral and also highlights the trend for doctors to prescribe so-called atypical anti-psychotics for their pediatric patients. The report’s nine-year analysis revealed that the use of these treatments—which can have serious side-effects that include weight gain and an increase in diabetes and other metabolic problems—in children has doubled over that time period. While atypicals are still more prevalent among boys, the rate of growth in girls aged 10-19 (130%) was the largest of all groups.

"Atypical antipsychotics are extremely powerful drugs that are being used far too commonly - especially in children - given their safety issues and side effects," commented David Muzina, a specialist in mood disorders and national practice leader of the Medco Therapeutic Resource Center for Neuroscience. "We're seeing them prescribed for a number of different conditions including depression and anxiety for which there is not good evidence that they are an effective treatment and yet we're exposing children to the possibility of extreme weight gain that could lead to a host of health problems including diabetes," Dr Muzina warned.

What’s also disturbing is that some 70-80% of drugs being used to treat children have only been approved for use in adults. And in some cases, especially when it comes to psychiatric drugs, they are also being used for “off-label” indications: for example, a drug approved to treat schizophrenia in adults is used to treat bipolar depression in children. The net result is that without national registries or wide-range clinical trials for many of these off-label drugs, children function as a giant, disorganized experimental pool where trial and error, not evidence-based medicine, is the rule of the day.

Children are not “small adults:” there are many questions still to be answered about how drugs affect neurological development, growth rates, metabolism and many other variables that are selectively affected at differing stages of development. The FDA’s Office of Pediatric Therapeutics has noted that increases in reports of central nervous system “events,” and other unique physiological responses to medication in children suggest that researchers may be considering the wrong endpoints when they are studying a drug’s safety profile.

It’s interesting that just over a decade ago, most of the controversy in pediatric therapeutics centered on the fact that due to a dearth of clinical trials involving children, there were few suitable drugs for treating pediatric problems. In response, in 1997 Congress authorized drug companies to receive a six month extension of patent protection for certain proprietary drugs if the companies conducted pediatric trials. These were drugs that the FDA believed might be beneficial in treating childhood conditions that had few therapeutic options.  In 2002 Congress went further and passed the Best Practices for Children Act  that renewed the 6-month patent extension for drug companies, but also mandated that an advisory group meet several times a year to review a wide range of  information received from doctors, clinical investigators and advocacy groups about medications for children.

The Act also requires that the advisory group (made up of representatives from the FDA, NIH and outside pediatric experts) publish a list at least every 3 years of drugs that should be considered as highest priority for government-funded clinical trials. These are almost exclusively drugs that are older and no longer have patent protection; and many are used to treat relatively rare childhood conditions. Finally, the 2007 FDA Amendments Act reauthorizes for five years the agency’s authority to require drugmakers to include assessments for pediatric use along with applications for new drugs or new uses for drugs.

Since 1997, about 350 drugs have had their labels changed to include pediatric indications—about 22% of the total number of drugs currently used to treat children. Dr. Alan Stiles, Chairman of Pediatrics at University of North Carolina and a member of the FDA/NIH advisory group says that the number of drugs that still need to be studied for use in children is enormous. “It’ll probably take 1,000 years to do this because it’s so expensive and it takes so long. Pharmaceutical companies have incentive to do this with proprietary drugs because they can get a patent extension, but there is no incentive for cheaper, generic drugs.” He gives the example of hydrochlorothiazide, a 30-year-old drug that is commonly used to treat hypertension and metabolic syndrome in adults. “This is not a drug that has had wide study in kids,” says Stiles, “and it would never be studied by pharmaceutical companies. But it’s a good, inexpensive, first-line treatment for kids.”

It makes far more sense to pharmaceutical companies to intead finance pediatric trials for their new, more expensive drugs. A 2008 article in the American Heart Journal looked at the economic results when companies took advantage of the FDA’s 6-month patent extension and performed pediatric studies on nine such name-brand hypertension drugs. The conclusion: although companies spent an average of  $5.2 million on safety studies and pediatric trials for each hypertension drug, the authors concluded: “the Pediatric Exclusivity Provision has generated highly variable, yet lucrative returns to industry sponsors.”

The increase in prescription drugs marketed for pediatric conditions will likely continue unabated. Obesity is a serious and growing problem among young people, and the diagnosis of behavioral disorders—and the accompanying pressure from schools, parents and practitioners to deal with them through medication—also shows no sign of slowing. As rates of hypertension, glycemic disorders, gastroesophageal reflux and asthma rise, so will the number of prescriptions written for kids.

The FDA’s policies that encourage drug companies to conduct pediatric clinical trials for their new proprietary drugs has brought mixed results. It has increased the sheer number of therapeutics available for treating difficult pediatric problems; but at the same time companies are also now driven to recoup their financial investment. They increase marketing of expensive, name-brand drugs—like the atypical antipsychotics—to doctors and even consumers (who often have few other sources of information on appropriate therapeutics for their young patients) and in some cases, drive inappropriate medication of kids. Meanwhile, information on how these drugs affect neurodevelopment, metabolism, growth rates and other long-term effects remains distressingly elusive.

What we urgently need is a saner system for monitoring the effects of a growing lexicon of prescription drugs used to treat our children. Along with that is a need for a broader, more accessible and comprehensive program for providing doctors with evidence-based recommendations for drug therapy. This issue has been in the forefront recently with the growing use of the newer atypical antipsychotic drugs in children and the need to monitor their long term metabolic effects. A 2008 article in Child and Adolescent Psychiatry and Mental Health details the need for stricter monitoring and reporting of all effects—beneficial, adverse, long-term, etc.—in children taking psychiatric drugs. Other groups have called for national registries to be set up so that doctors and investigators can record pediatric clinical information—helping to create a large database to help identify best treatments for various psychiatric problems in kids. This same approach should be considered for cardiovascular drugs and all others that have been used primarily in adults.

The Medco report provides evidence of a new reality. Due to an epidemic of obesity, an increase in diagnosis of behavioral and mental health problems and, in some cases, better drugs for controlling widespread conditions like asthma, children are now an attractive—and growing—market for drug companies. But first, caution. The dearth of knowledge concerning dosing, contraindications, long-term effects and just plain suitability for children of many drugs is striking. The solution is for the FDA and NIH to devote more resources to conducting evidence-based studies, creating national registries and putting together treatment guidelines for pediatric therapeutics. This particular national resource is to precious to leave to chance.

 

Comments

[Sam Kiva]

It seems a shame to start children on a drug regiment this early.
I hope profits do not overshadow health.
S.