FDA News (Full Article)f1

FOR IMMEDIATE RELEASE
P04-45
April 19, 2004

Acting FDA Commissioner Dr. Lester M. Crawford Outlines Science-Based Plan for Dietary Supplement Enforcement

Speaking before the American Society for Pharmacology and Experimental Therapeutics (ASPET) and the American Society for Nutritional Sciences, Dr. Lester M. Crawford, Acting Commissioner of the Food and Drug Administration (FDA), today outlined the agency's science-based approach to protecting American consumers from unsafe dietary supplements.

Dr. Crawford said the agency would soon provide further details about its plan to ensure that the consumer protection provisions of the 1994 Dietary Supplement Health and Education Act (DSHEA) are used effectively and appropriately. Through DSHEA, which sets up a distinct regulatory framework for dietary supplement products, Congress attempted to strike a balance between providing consumers access to dietary supplements and giving FDA regulatory authority to act against supplements or supplement ingredients that present safety problems, are marketed with false or misleading claims, or are otherwise adulterated or misbranded.

"FDA is absolutely committed to protecting consumers from misleading claims and unsafe products," said Dr. Crawford. "Unlike most foods, some dietary supplements are pharmacologically active. And we have seen over the last 10 years a huge growth in the dietary supplements industry, including the introduction of products that seem far removed from the vitamins and minerals of the pre-DSHEA days. We have become increasingly aware of the potential health problems some of these products pose."

In the last 6 months, FDA has inspected 180 domestic dietary supplement manufacturers; sent 119 warning letters to dietary supplement distributors; refused entry to 1,171 foreign shipments of dietary supplements; and seized or supervised voluntary destruction of almost $18 million worth of mislabeled or adulterated products. "We will continue to aggressively enforce DSHEA against unsafe or mislabeled products," Crawford said.

In March FDA requested that 23 companies cease distributing dietary supplements containing androstenedione, which are marketed to stimulate testosterone and muscle growth but have anabolic steroid effects in the body.

Over the next several months FDA will provide additional information to explain and implement the tools available to the agency under DSHEA to act against unsafe supplements and false or misleading supplement labeling claims.

FDA is also developing regulations for industry on good manufacturing practices (GMPs). When finalized, this rule, proposed last spring, will help protect consumers from dietary supplements that contain impurities or contaminants as a result of how they are manufactured or handled.

FDA is, in addition, putting dietary supplement labeling under closer scrutiny. Dietary supplement labels cannot claim the supplement will treat or cure a disease, and since December 2002 FDA has worked with the Federal Trade Commission to challenge false claims of supplement effectiveness for treating a range of diseases.

To support its consumer protection actions, the agency is developing approaches to systematically review the evidence about the safety of individual dietary supplements. FDA expects to evaluate the available pharmacology, published literature (including animal, in vitro, epidemiological and clinical trial data) evidence-based reviews, and adverse event information -- the approach that formed the scientific foundation for FDA's recent rulemaking on ephedra.

Supplement labels can make claims about the impact of a supplement on the structure or function of the body, but the claims must be truthful and not misleading. Two weeks ago, FDA sent warning letters to 16 firms to stop making false claims for weight loss. The FDA plans, in addition, to issue guidance on what data would substantiate such claims.

FDA's rulemaking on dietary supplements containing ephedrine alkaloids became effective on April 12, 2003. Last week the federal district court supported the agency's rule by declining to issue a temporary restraining order sought by the industry.

When DSHEA was passed a decade ago, there were about 4,000 supplements on the market, including vitamins, minerals, amino acids, and herbs and other botanicals. Congress determined that these products were more like foods than drugs, which cannot be put on the market unless a high threshold of evidence about their safety and efficacy is met, and that, like foods, such dietary supplements should in general be given the benefit of the doubt as to safety.

A recent Institute of Medicine report, sponsored by FDA, estimated that American consumers spend $18 billion annually on dietary supplements and that there are about 29,000 such products on the market, with another 1,000 new products introduced each year.

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Damaging Drug Study? Bury It (Full Article)f2
By Kristen Philipkoski
02:00 AM Apr. 22, 2004 PT

The risks for children taking some antidepressants could outweigh the benefits, according to an analysis of data that pharmaceutical companies did not make widely available to the public or to researchers.

Researchers in the United Kingdom analyzed 22 randomized controlled trials that compared the effects of antidepressants and placebos in children from 5 to 18 years old. Data on four out of the five antidepressants examined showed the drugs had the potential to do more harm than good in depressed kids, according to research published in the April issue of the British medical journal The Lancet.

About half of the results had not previously been published in medical journals, so researchers and doctors didn't have access to them. The published data showed the drugs benefited young patients with depression. But when the unpublished results were factored in, the risks outweighed the benefits, the researchers said. It's unclear why the studies were not published, but critics accuse pharmaceutical companies of withholding studies that didn't turn out the way they hoped.

"We can't tell what motivates the pharmaceutical companies involved, but we do know that some probably don't publish for that reason, given recent reports," said Dr. Craig Whittington, the lead researcher on the Lancet paper and a researcher at the University College of London, referring to a recent study published in the Canadian Medical Association Journal that said executives of GlaxoSmithKline (the maker of Paxil) had advised members of their staff to withhold data about antidepressants' effects on children.

The research in question addressed only children with depression. The drugs might be safe and effective for treating children with obsessive-compulsive disorder, anxiety or other problems, the U.K. researchers said.

Fluoxetine, or Prozac, was the exception. The Lancet analysis found the drug could help depressed children. But evidence on sertraline (Zoloft), citalopram hydrobromide (Celexa) and venlafaxine (Effexor) showed the drugs didn't do the children any good, and might actually be harmful.

The researchers examined the incidence of risk factors as reported in the studies, such as "suicide, suicide attempt, suicidal tendency, non-accidental overdose and thoughts of self harm," Whittington said.

The Lancet study comes in the midst of a debate over whether antidepressant drugs -- also called selective serotonin reuptake inhibitors, or SSRIs -- might cause some children and adolescents to commit suicide. In 2003, the United Kingdom's Committee on Safety of Medicines prohibited the treatment of childhood depression with any SSRI except Prozac. The U.S. Food and Drug Administration has ordered pharmaceutical companies to include warnings on drug labels, but stopped short of prohibition.

"In view of the high risk of suicide in this group of children and young people, the possibility that a drug might increase that risk without clear evidence of benefit, should, in our view, discourage its use," the authors wrote in The Lancet paper.

Vera Hassner Sharav, founder of the advocacy group Alliance for Human Research Protection, says the FDA has known about the potential suicide risk in children since at least 1996, and that the agency has put children's lives at risk by not disclosing that information.

"How will FDA officials defend their failure to protect children from the hazards of antidepressants before a Congressional committee, inasmuch as they knew the content of the unpublished data for years?" Sharav wrote in an e-mail.

Sharav points out the suicide rate among adolescents has actually increased since SSRI antidepressants have been prescribed for youth. From 1980 to 1997, it increased 11 percent for 10- to 15-year-olds, and 109 percent in kids from 10 to 17 years old, according to the Centers for Disease Control and Prevention.

The House Committee on Energy and Commerce recently warned it might launch an investigation into the FDA for holding back crucial information about the dangers of antidepressants for some children.

"In a global medical culture where evidence-based practice is seen as the gold standard for care, these failings are a disaster," wrote Lancet editors in an editorial accompanying the data analysis.

Critics accuse pharmaceutical companies of valuing profits over patients. Global sales of Paxil in 2003 were $4.97 billion.

The FDA, GlaxoSmithKline and Pfizer (maker of Zoloft) did not respond to requests for comment for this article.

"This debate about the SSRIs is overdue," said Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. "We're in a classic situation where because of liberal off-label prescribing practices in the U.S. and heavy direct-to-consumer advertising, we've got basically a load of kids getting drugs for which they've never been tested."

Off-label prescribing is the legal practice of prescribing an FDA-approved drug for disorders other than those for which it has been specifically approved.

But experts also cautioned that it could be even more dangerous to yank fragile children, especially teenagers, off antidepressants when the medication very well might be helping them. The most important part of drug treatment for depression is monitoring its effects and calibrating it accordingly, because everyone's response is different, said Alice Sterling Honig, a psychologist and professor emerita of child development at Syracuse University.

"With a little antidepressant, a little Zoloft or a little Prozac, maybe he'll cheer up enough so psychology can help him," Honig said. "At least it could let him talk to me, because with depression sometimes people don't want to talk at all."

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