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Prepared Witness Testimony The House Committee on Energy and Commerce
Issues Relating to Ephedra-containing Dietary Supplements.
Subcommittee on Oversight and Investigations
Dr. Raymond Woosley M.D., Ph.D.
Mr. Chairman and members of the Committee: Thank you for the opportunity to testify before the Committee on the very important topic, i.e. the dangers of dietary supplements that contain ingredients from the plant ephedra or the chemical ephedrine. Since 1995, I have served as a consultant to the Center for Food Safety and Nutrition of the Food and Drug Administration to address their concern over the large number of severe adverse reactions with ephedrine-containing dietary supplements reported to the FDA. In 2001, I was awarded the FDA Commissioner's Special Citation for my work on ephedrine for the FDA. I have no financial interests in this question and I do not represent any particular organization. I have consistently recommended that the FDA take steps to have non-prescription products containing ephedrine removed from the market. In 2001, I joined Public Citizen, a consumer advocacy organization, and filed a citizen's petition calling for an FDA ban on ephredrine-containing dietary supplements. I base this recommendation on my almost forty years of experience as a scientist and physician studying the actions of drugs in humans. In 1967, I obtained a PhD in pharmacology, i.e., the study of the actions of drugs. I obtained an MD from the University of Miami and then trained in Internal Medicine at Vanderbilt University. I then completed a fellowship in the subspecialty of clinical pharmacology, i.e. the study of the actions of drugs in humans. I rose to the rank of Professor of Medicine and Pharmacology at Vanderbilt University before moving to Georgetown University School of Medicine to Chair the Department of Pharmacology. I am now Vice President for Health Sciences at the University of Arizona and Director of one of the seven Centers for Education and Research on Therapeutics funded by the Agency for Healthcare Research and Quality. For the last 39 years I have studied the actions of drugs. I have been asked to serve as an advisor to the NIH, the FDA, the DOD and all of the leading pharmaceutical companies on the actions of drugs in humans. My experience has given me a broad perspective and an expertise in the toxicity of drugs. I served as co-director of the NIH-sponsored Cardiac Arrhythmia Suppression Trial that found certain drugs designed to save lives were actually causing tens of thousands of deaths each year. I also served as leader of the team that determined the mechanism of cardiac toxicity caused by terfenadine (SeldaneŽ) which served as the basis for its ultimate removal from the market. I currently lead a team of scientists who are studying 50 prescription drugs that have the potential to induce life-threatening arrhythmias. In 1995 and again in 2000, I was asked by the FDA to review over 230 reports of adverse events related to the use of dietary supplements containing ephedra alkaloids. The following is the conclusion of my most recent report: "The occurrence of serious side effects makes the use of ephedrine containing products as dietary supplements at dosages that can increase blood pressure and heart rate in susceptible individuals unacceptable without medical supervision." Many agencies and regulatory bodies such as Health Canada have already taken action to protect the public from ephedrine-containing products. Two states have banned the sale of these products and the California legislature is now considering such action. The US Military and the National Football League prohibit the use of ephedrine-containing products. The American Medical Association, the American Heart Association, the American Society for Clinical Pharmacology and Therapeutics, and many other professional organizations have called for FDA action to remove these products from the market. Dozens of deaths reported to the FDA and an unknown number of unreported deaths are reason enough for the FDA to take action. However, a year ago, the FDA refused to act on our petition and called for further study. They contracted with the RAND Corporation to perform an analysis of the published studies and FDA reports of adverse events that might pertain to the safety and effectiveness of dietary supplements containing ephedrine or ephedrine with caffeine taken for weight loss or exercise enhancement. However, such an analysis is not relevant to the way ephedrine is used by the public. Since these products are taken as non-prescription "dietary supplements", they are used without any medical screening or medical supervision. However, the scientific papers that were analyzed by RAND were studies in which subjects had been screened for pre-existing medical conditions and were followed during the trials under medical supervision. As an example, in the study by Boozer et al. (Int. J. Obes. Relat. Metab. Disord. 26(5):593-604, 2002) that is often cited as evidence for the safety of these products, the investigators excluded one of every ten subjects they screened because they found medical conditions that made ephedra/caffeine, in their estimation, unsafe. RAND could not find published trials that truly addressed the question posed by FDA. Such studies without medical screening are not feasible or ethical because of the general knowledge in the medical community that ephedrine-containing products are dangerous. Any Institutional Review Board responsible for the protection of human subjects would not approve a research protocol unless it included medical screening and monitoring for safety. It is therefore not surprising that the published reports that include only small numbers of subjects who had been medically screened failed to detect the type of toxicity reported to the FDA. The ephedrine industry has raised doubts about the validity of the adverse events reported to the FDA. Determination of causation for rare adverse events can be difficult when analyzing a single report. However, one must consider the totality of evidence for scientific validity and consistency with the drugs pharmacologic actions. After considering the information in the adverse events reported and the totality of information about ephedrine, I concluded that the use of these products causes a serious health risk to the public. Decades of experience summarized in textbooks of medicine and pharmacology support this conclusion. The RAND analysis of these reports failed to adequately consider the pharmacology and clinical pharmacology of adrenaline-like chemicals such as ephedrine. Also, the consistency of the evidence across a range of chemically-related substances must be considered. The relative safety and efficacy of other drugs that have similar pharmacologic actions is especially relevant. Every drug with adrenalin-like actions that increases blood pressure and heart rate, i.e. they mimic the human body's emergency "autonomic" nervous system, has been already associated with serious cardiovascular and neurologic adverse events. Likewise, the actions of drugs that antagonize the effects of ephedrine should be considered. For example, drugs that block the actions of adrenaline reduce the incidence of strokes and heart attacks. The ephedrine data are consistent with the observation of a high risk of stroke with the diet pills containing phenylpropanolamine (PPA), a drug with almost the same chemical structure as ephedrine. In this case, the FDA took action to remove products with PPA from the market. Another related weakness of the RAND assessment is the absence of consideration of the genetic diversity that we know exists in large populations of people. Most of the studies reviewed enrolled only 50-200 patients and all had been medically screened. It is very unlikely that these studies would include any of the 1 in 10,000 patients at risk for super-sensitivity to ephedrine due to a genetic variant that would be otherwise silent. The available evidence clearly shows that these products cause harm in some individuals that cannot be prevented by warning labels because most patients will not know they are at risk of experiencing adverse effects. Based upon the Boozer trial, approximately 10% of patients will have medical conditions that place them at increased risk of adverse effects. I hope you will take swift action to protect these people. Recommendations In summary, I strongly encourage you to ask the FDA to ban these products. I have no doubt that these products are causing needless death and disability to people. I also ask you to consider enacting legislation that will more accurately distinguish between "drugs" and "dietary supplements" and clarify how the FDA should regulate these products. Many of the products that are marketed as dietary supplements and especially the ephedrine-containing products are in fact drugs because they are not normal constituents of a healthy diet. The ephedrine products are being used by and being promoted to the public for weight loss. Without medical supervision these products present a clear and serious danger to the public and should be regulated as medicines and banned for use without a prescription. Thank you for the opportunity to provide this statement for the record.
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