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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. Carol Boozer D.Sc.
Introduction Thank you for the invitation to speak to you today. I am Dr. Carol Boozer. I received my doctorate of science in nutrition from Harvard University, School of Public Health. I am presently on the faculties of the Institute of Human Nutrition, in the Department of Medicine at Columbia University and at the New York Obesity Research Center at St. Luke's-Roosevelt Hospital in New York. I have received research funding from the National Institutes of Health and have served on NIH study sections and as an NIH site visit reviewer. I currently receive significant research support from NIH grants. My career has been devoted to research in the areas of nutrition and obesity with the intention to promote public health. Ephedra Studies Issues relating to ephedra are highly controversial. My interest in this issue is through my role as a scientist who was the principal investigator in two of the very few clinical trials of the efficacy for weight loss and safety of herbal ephedra/caffeine combinations. My position today is to promote the role of science in the policy making process in general and in this issue in particular. The sudden death of any individual is tragic to the family and friends and a loss to the country. The effort to reduce the number of these tragedies and promote public health should be the highest priority. Reports of adverse events related to the use of ephedra must be taken seriously, and they are useful in pointing to areas that require research. They do not constitute scientific proof of an association between ephedra consumption and injury. The reason why such reports cannot prove cause and effect is easily understood by the following example. If a city is considering whether installation of a traffic light has reduced accidents at a dangerous intersection, both the accident rate before the installation, the "background rate" and the rate after installation must be known. However, even if both rates are known, a difference in rates might not be due to the light itself since other factors such as weather, condition of the road, or the opening of a bar in the area could affect the rate. A reduction in the accident rate following installation of the light cannot, in and of itself, prove that the light caused the change. Methodology Scientists have carefully considered the methodology required to show causality. The "gold standard" method in clinical studies is the randomized, double-blind, placebo-controlled trial. Randomization is a process whereby individuals are assigned to treatment groups in such a way that the two groups are similar in all other characteristics, except for the treatment under study. This controls for the possibility of even unknown factors affecting one group differently from the other. Double-blinding insures impartiality, since throughout the study neither the participants nor the investigators know the treatment group of any participant. Finally, inclusion of a placebo group allows assessment of the background rate, in a group that is similar in all aspects to the treatment group, except for the treatment under study. The two clinical trials of ephedra-containing products that I conducted were both randomized, double-blind, placebo-controlled studies undertaken to assess the efficacy for weight loss and safety of herbal/ephedra combinations. A statistician not involved in carrying out the studies provided the randomization codes using a system that would maximize the chance that placebo and treatment groups would on average be similar in characteristics such as age, body weight, gender distribution, income, education, etc. Since none of the research staff involved in the study knew the codes, there was no way that they could bias the results by treating one group differently from the other during the study. Only after the study was completed and after the data had been entered into computer spreadsheets was the code broken by the statistician who analyzed the data. The data for the group receiving the ephedra was then compared with the data for the group receiving placebo. Since the groups were similar at the start of the study and followed the same protocol with the exception of the treatment, herbal ephedra/caffeine or placebo, any differences that were found could be attributed to the treatment. These two studies were the only clinical trials of ephedra and ephedrine that were given the highest ranking for quality in the recently published Rand Report. Results The two studies together included 234 men and women who were overweight, but otherwise healthy. Half received herbal ephedra/caffeine and half placebo. One study continued for 8 weeks, the other for 6 months. In both studies, those receiving the herbal treatment lost more body weight and body fat and had improved blood lipids compared with those receiving placebo. No individual in either study experienced a significant adverse event (defined in the scientific community as death, heart attack, stroke, etc.). In both studies, the herbal groups had increased heart rate and slightly increased blood pressure relative to placebo groups. Heart monitors, used in the 6-month study, showed that herbal treatment did not increase heart irregularities. Drop-out rates were similar in the herbal and placebo groups in both studies, but in the 8-week study, the reasons given for dropping out of the herbal treatment group included more self-reported side effects (primarily palpitations). In the 6-month study, the numbers of individuals who dropped out due to side effects were very low and were similar between the two groups. The side effects reported more frequently by all subjects in the herbal groups compared with placebo groups were: dry mouth, insomnia, headache and heartburn. Reaction These studies were published in the International Journal of Obesity. & Prior to publication, experts in the field critically reviewed each paper and made recommendations to the editor as to the validity of methods, interpretation of results and scientific importance, a process called peer-review. Subsequent to publication, there have been attacks on the studies by the media and others. The public is not well served by suppression of scientific studies. The value of scientific study does not depend on agreement of outcome with preconceived expectation. While no study is perfect, these studies were conducted without pressure from the industry sponsors for a predetermined outcome, as evidenced by their contractual agreement to publication of results regardless of outcome. The studies were conducted with impartiality that was assured by the randomized, double-blind, placebo-controlled design. They were subjected to peer-review and published in a reputable scientific journal. Rejection of scientific data in favor of anecdotal stories is inconsistent with the advancement of knowledge or responsible public health policy. The Rand Report reviewed approximately 20,000 adverse event reports. They classified events as "sentinel" if they provided three things: 1) documentation that the event did occur, 2) documentation or toxicological evidence that the subject had consumed ephedra within 24 hours prior to the adverse event, and 3) evidence that an adequate investigation had assessed and excluded other potential causes. Only 21, approximately 1 in 1,000 reports, reached this level and only two of these were deaths. One estimate of ephedra consumption in the United States was 12 million people in 1999. Among such a large number of people, some adverse events would occur whether or not individuals were taking ephedra. Data from the U.S. Government's Division of Vital Statistics estimates the death rate from heart disease alone to be roughly 1 in 5,500 even in young individuals, age 25-44 years. Among the millions of people consuming ephedra, the background rate of deaths and other serious adverse events would be in the thousands, many fold higher than the 21 documented sentinel events. That is why the Rand Report states that "classification as a sentinel event does not imply a proven cause and effect relationship." While efficacy of ephedra in promoting weight loss is established, it is not my position that the safety of herbal ephedra is proven for different populations or with different usage. Additional research would be required to determine effects in people who are not healthy, or who consume ephedra at levels above those studied, or for periods longer than six months, or in combination with prescription or illicit drugs. But, at present, there is no scientific data proving that consumption of ephedra/caffeine combinations for weight loss are unsafe, when consumed in accordance with appropriate warning labels. Additional research on the effects of ephedra on weight loss and in other areas, such as athletic performance, is clearly needed. I urge those who are responsible for policy to promote such research and to be guided by its findings.
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