Opinion ID: 76908
Heading Depth: 2
Heading Rank: 3

Heading: Reliance on Other Studies and Reports

Text: 56 O'Donnell also relied on several other studies to support his opinions about the toxicity of ephedrine and caffeine. A close analysis of the studies, however, shows that they do not authorize his opinions. The authors of the articles limit the application of their studies consistent with the principles of good science; O'Donnell expands the application beyond good science. 57 O'Donnell relied heavily on a report by Haller and Benowitz published in the New England Journal of Medicine that concluded that the ephedrine/caffeine combination in some patients may cause toxicity. Christine A. Haller & Neal Benowitz,  Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids,  343 NEW ENG. J. MED. 933-38 (2000) (emphasis supplied). The authors studied 140 adverse incident reports from persons who took dietary supplements containing ephedra alkaloids. Id. The authors said that these interactions between phenylpropanolamine and caffeine support the idea that the combination of ephedrine and caffeine could increase the risk of adverse effects. Id. (emphasis supplied). The authors, however, admit that their study does not offer a basis to determine the incidence of serious adverse effects of ephedrine alkaloids, and they recognize the necessity for study of the determinants of individual susceptibility to serious adverse effects of dietary supplements containing ephedra alkaloids so that the appropriate guidelines and warnings can be devised. Id. Moreover, O'Donnell agreed that Haller and Benowitz concluded from this study that the use of dietary supplements that contained ephedra alkaloids may pose health risks to some persons. Id. (emphasis supplied). He further conceded that the authors sent a letter to the editor explaining that the study did not prove causation. 58 In the same volume of the New England Journal of Medicine, Dr. G. Alexander Fleming published an editorial entitled The FDA, Regulation, and the Risk of Stroke, in which he discusses the Haller and Benowitz study that O'Donnell considers so important. 343 NEW ENG. J. MED. 1886-87 (2000). About that study Fleming stated: the study by Haller and Benowitz represents only an early step in the process of pharmacologic vigilance. Data from spontaneous reports usually provide only preliminary evidence of risk and not proof of risk. Id. Fleming reviewed the eleven cases of sudden catastrophic cardiovascular and cerebrovascular events that Haller and Benowitz attributed as definitely or probably caused by ephedra alkaloids. Id. He concluded that only one of the cases should be attributed to supplements containing ephedra alkaloids. Id. He reached this conclusion in substantial part because of the background risk of subarachnoid hemorrhage and myocardial infarction. As he explained, subarachnoid hemorrhage and myocardial infarction are too common, even among young and middle-aged people to be pathognomonic of complications of the use of products containing ephedra alkaloids. Id. He acknowledges the importance of background risks in reaching conclusions about toxicity and individual injury. Id. Fleming went on to explain that 59 it is much less clear whether the FDA should take steps to ban or even restrict the use of products containing ephedra alkaloids. The risks of such products, when they are used as directed, have not been adequately established. A large body of data suggests that products containing ephedra alkaloids and ephedrine as an over-the-counter drug have a low risk of adverse effects at the recommended levels of consumption. The report by Haller and Benowitz provides information that justifies the initiation of the same kind of study that was conducted by the Hemorrhagic Stroke Project. 60 Id. 61 Fleming neither exonerates nor indicts ephedra alkaloids, but he does explain the limitations of the Haller and Benowitz study which, in turn, shows that O'Donnell does not follow the conservative approach of scientists in this field. Dr. Fleming exemplifies this approach by limiting conclusions about causation from insufficient evidence. Indeed, Haller and Benowitz limit the conclusions authorized from their study by saying that it does not prove causation. The comments of Fleming and Haller and Benowitz demonstrate the intellectual rigor in this field of science, an intellectual rigor that is conservative and does not leap to specific conclusions about causation or toxicity from incomplete evidence or broad principles. But the record offers yet more evidence of O'Donnell's willingness to exceed the limits of the conservative scientific methodology. 62 He also relies on an article called  Adverse Cardiovascular Events Temporally Associated with Ma Huang, an Herbal Source of Ephedrine  published in the Mayo Clinic Proceedings. David Samenuk et al., 77 MAYO CLIN PROC. 12-16 (2002). The author studied adverse reaction reports filed with the FDA by consumers of ma huang, a natural source of ephedrine. The study focused on the safety of ma huang for adverse cardiovascular effects. Id. Of the 926 complaints studied, 37 involved serious cardiovascular events. Id. at 15. But the authors of the study explained that their report must be interpreted as demonstrating only a temporal, not a causal, relationship between ma huang (ephedrine) and the adverse cardiovascular events. Id. at 13. The authors further explained that [o]ur report has the limitation of being an observational study and as such does not definitively establish the relationship between ma huang use and the risk of adverse cardiovascular events. But this shows again O'Donnell's lack of scientific rigor in that he draws unauthorized conclusions from limited data — conclusions the authors of the study do not make. 63