Alliance for Human Research Protection

Pediatric Drug Tests_CNN / NYT Editorial

Children are increasingly being exploited for profit by the biomedical industry. Between 1983 and 1997, children had been protected from medical experiments that are not in their best interest. But in 1997 Congress passed the FDA Modernization Act (FDAMA), providing a six-month extension on patent exclusivity to drug companies that test their patented and new drugs in children. The Wall Street Journal reported that patent extension for a blockbuster drug can mean $284 billion and $995 for a drug company. The law was passed without an impact assessment study. Indeed, Congress failed to balance the financial incentives for industry with improved safeguards to protect young children from exploitation. No provision in that law ensures that the child's best interest will be protected.

New proposals for increased recruitment of children are being considered by Congress - again without any provision to protect the best interest of the child subjects. S 2394 is sponsored by Sen. Hilary Clinton, Sen. Christopher Dodd, and Sen. Michael DeWine. A NY Times Editorial (Oct 14) unhesitatingly promotes efforts to "push ahead with legislation that would require all drugs to be tested for safety and efficacy in children, not just in adults."

By contrast, more thoughtful articles and opinion pieces present the profound ethical dilemma presented by the issue of using children--who cannot refuse to consent--in clinical trials. The children are, in fact, exposed like "canaries in the mines" to test the safety of drugs so that (it is claimed) other children could benefit. For example, an Opinion piece by Jeffrey Kahn, Center for Bioethics, University of Minnesota (below) and a five-part series in Parenting Magazine, The Drug-Testing Debate By Jennifer Wolff. [http://www.parenting.com/parenting/article/article_general/0,8266,7768, 00.html ]

Those who claim that clinical trials are essential for providing treating physicians with guidelines for prescribing drug doses for children, pretend that no guidelines exist. In fact, a widely used and highly acclaimed guideline exists: The Harriet Lane Handbook, published by Johns Hopkins Hospital, which is in its 16th edition --is available in pocket size and electronic version! http://www.medicalpocketpc.com/articles/review_harriet.shtml

Drug safety studies can be very hazardous for the children involved. FDA refuses to provide the data about adverse events from pediatric trials. AHRP asks: how many healthy children have been harmed in clinical trials? How many children who participated in clinical trials died? Congress should ask the FDA and NIH to provide the data from previous trials so that they can assess the impact on children before passing additional legislation that will target more children for drug testing that may be hazardous for their health.

Since FDAMA, children who are legally precluded from exercising the right to refuse are being aggressively recruited to bear the burden of testing drugs that may (or may not) be in their best interest. Children are being sought as drug testing subjects to enrich the drug companies. What’s more, children who do not have a life-threatening condition are being put in harm’s way. For example, psychotropic drugs are an especially lucrative market for the drug industry--the incentive to extend that market to children is obvious. Children who may or may not have a condition for which the drugs were approved for adults, are being subjected to the adverse effects without a benefit.

The value of clinical trials for clinical practice is a matter of dispute. For example, a meta analysis of FDA’s antidepressant drug trial data by Irving Kirsch, Thomas J. Moore, and Alan Scoboria and Sarah S. Nicholls: http://journals.apa.org/prevention/volume5/pre0050023a.html Similarly, Dr. David Healy, wrote: "there is in principle no need for any drug studies in children for either anti-psychotics, antidepressants or for treatments for OCD for example. Research conducted in children or adolescents with such conditions will in fact only produce a situation in which companies gain a license to vigorously promote their treatments for these conditions."

Although the scientific literature rarely, if ever, mentions suicide in clinical trials, the recent findings by Dr. Arif Kahn who analyzed FDA's clinical trial data involving 71,604 patients (1985-2000) who were tested psychotropic drugs confirms what others have suggested based on partial data: the suicide rate in adult clinical trials testing all psychotropic drugs is extraordinarily high - despite the exclusion of those who were suicidal: http://www.ahrp.org/infomail/0902/06.html

There is evidence revealing that pediatric drug trials testing psychotropic drugs are not designed to ensure that risks to the children involved are minimized. Indeed, children are being exposed to preventable, severe adverse reactions in experiments designed to test dose tolerance.

The following is but one example: in a series of pediatric studies conducted by Pfizer testing it's antidepressant drug, sertraline (Zoloft) “Doses were pushed up to find out if they would become intolerable [for the children]-- “despite evidence published 10 years earlier from adults that sertraline induces dose dependent agitation and the dose to which sertraline was pushed in these children could have reliably been expected to produce agitation. http://www.ahrp.org/children/healy0402.html

Dr. David Healy's examination of Pfizer's expert report about its pediatric trials submitted to the FDA, "makes it clear that there were in fact at least six children who made suicidal acts while on sertraline and more who became suicidal." Pfizer maintains these suicidal acts occurred among 44 children classified as depressed. If that is the case, Dr. Healy points out, then the rate of suicidal acts in children given Sertraline, represents "a 20-fold higher rate of suicidal acts than appear in the sertraline-treated adult literature." [See: David Healy MD, Testing Psychotropic Drugs in Children http://www.ahrp.org/children/healy0402.html

How many children have been recruited for drug trials designed to test the safety and efficacy of psychotropic drugs? Have the senators sponsoring legislation to broaden the recruitment of children for clinical trials been informed about the suicide rate in some pediatric trials testing psychotropic drugs --that even surpass the extraordinary suicide rates in adult trials? Shouldn’t Congress and the Administration be concerned about recruiting children for trials that expose them to risks of suicide?

The FDA has acknowledged that before FDAMA the use of children as subjects in phase I safety drug studies "had been primarily limited to life threatening diseases and children who had the disease" in question. Prior to FDAMA children were protected from harmful experiments in accord with federal regulations (45 CFR 46.404-409). In 1999 the FDA acknowledged that the post-FDAMA policy change "led to an increasing number of proposals for studies of safety and pharmacokinetics, including those in children who do not have the condition for which the drug is intended."

In 2001 the Boston Globe reported that children had suffered and died in clinical trials in which ethical standards had been violated. Neither Congress nor the senators--Clinton, DeWine and Dodd-- who are promoting legislation legitimizing the use of other people's children as drug test subjects have even addressed the immoral practice of giving financial incentives for parents, physicians, and researchers, to "volunteer" and refer children for medical experiments that may result in undermining the children’s health and welfare.

The children who will be used as "canaries in the mines" to test drugs for market expansion purposes will not come from affluent families--such as the editorial board of The NY Times, or Congress or FDA officials. The "canaries" are likely to come from disadvantaged, poor families for whom the financial enticements are a form of coercion. It is appalling that the government is pushing unsuspecting families to lend their children for what the courts would characterize as child abuse.

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http://www.cnn.com/2002/HEALTH/10/15/ethics.matters.peds.research/index. html

Research in kids: Why it's risky, why it's important By Jeffrey P. Kahn, Ph.D., M.P.H. Director, Center for Bioethics University of Minnesota Tuesday, October 15, 2002 Posted: 2:22 PM EDT (1822 GMT)

(CNN) -- Federal policy for biomedical research on children has come to a crossroads because of a convergence of circumstances, and the next step is vitally important.

For starters, the U.S. Senate is about to consider a bill that would require all drugs sold and marketed in the United States to be tested on children as well as adults.

It may seem surprising that this isn't already the case, but most drugs prescribed for children have been tested, in controlled settings, only on adults.

Doctors then order lower doses for children, but it's an inexact science because children are not just small versions of grownups.

So a policy that requires testing explicitly for safety and efficacy in children is long overdue, and this bill – stemming from a recent, but challenged rule by the Federal Drug Administration -- would make it happen.

New biomedical frontiers, new problems This policy decision comes at a critical time in biomedical research.

Gene therapy research has been put on hold after what appeared to be success stories -- in three children with a genetic type of immune deficiency -- suffered a setback when one of the children developed leukemia from the treatment.

And the family of a deceased artificial heart recipient is suing. They say the patient didn't understand all that was involved in the research project.

As these cases should teach us, research we hope will improve drugs for future children requires risks to those involved in the research today.

Should children be exposed to these risks of research so that other children can benefit?

Calculated risks, geared to children As a society, we want the benefits of biomedical research, and we want those benefits to be shared as widely as possible -- especially with the most vulnerable.

But benefits come with costs, one of which may be injury to those very people we hope to help.

Our research policies have focused on protecting children as much as possible from risks. Unfortunately, that didn't mean children weren't harmed. It means the harm occurred when drugs developed for adults were used in children through trial and error and without the benefit of a controlled scientific setting.

We now have an opportunity to change that and test drugs for children just like we test drugs for adults -- on the populations that will eventually use them and in controlled settings.

But that doesn't mean we should do it in just the same ways as we do in adults. Since children can't decide for themselves whether to participate in drug trials, we should make sure parents or guardians understand all the risks and benefits.

For example, parents shouldn't receive benefits, such as payments, in return for their children participating. Also, the risks should be markedly less than those we tolerate in adult drug trials. This might mean testing drugs on children later in the testing process, after early-stage trials on adults have proven safety. That way we can protect children in research while reaping the benefits of pediatric research.

The reality is that if we want a future that includes effective drugs for our children, it's time to move past pint-sized drug research policy.

Visit the "Ethics Matters" Archive where you'll find other columns from Jeffrey Kahn on a wide range of bioethics topics.

"Ethics Matters" is a biweekly feature from the Center for Bioethics and CNN Interactive.

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http://www.nytimes.com/2002/10/14/opinion/14MON2.html?pagewanted=print&position=top

NEW YORK TIMES EDITORIAL October 14, 2002 The Need for Pediatric Drug Tests

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