Troubling Ephedra Research

The problem: between 1995 and 2003, FDA held a number of hearings to consider whether ephedra posed an unreasonable risk to public health when used as directed. In 1997 the agency proposed to regulate ephedra as a drug, only to be thwarted by DSHEA and industry stakeholders. More recently, following the sudden death of Steve Belcher and the discovery of over 13,000 previously undisclosed adverse event reports from persons taking this product, FDA renewed these efforts and subsequently announced its intention to ban the sale of ephedra as a dietary supplement. During this same period, industry stakeholders sponsored clinical trials of ephedra and ephedra compounds, the results of which were heavily advertised as the gold standard proof of safety and efficacy. These claims came under sharp scrutiny within the last year and a half as evidence from civil litigation became public and a striking collection of documents were released to the public in July 2003 by the House Committee on Energy and Commerce in the course of its investigation of ephedra. These documents, including sponsor and investigator correspondence, internal FDA memoranda, depositions, institutional correspondence, and data from clinical trials, appear to paint a dismal picture of scientific misconduct, IRB lassitude, and regulatory impotence coupled with a complete and utter disregard for the rights and welfare of the human beings enrolled in these studies. Perhaps the most remarkable document we've come across is the 300-plus page deposition of the principal investigator for the two most respected clinical trials, which Senators Kennedy and Durbin and Representative Waxman submitted into the public record through the FDA Dockets. The deposition points up an alarming number of gaps in our feeble system of research protections, and taken as a whole, forms some of the strongest evidence supporting the need for statutory protection of human research subjects.

Some of the more alarming allegations to surface were:

• after the initial IRB demanded the sponsor secure an IND, the sponsor went shopping for another presumably less fussy IRB
• one IRB approved 2 clinical trials through expedited review, and did so at least in part according to the investigators, because the sponsor offered a bonus payment for speedy approval
• the test products in 2 clinical trials may have been contaminated with pharmaceuticals
• mislabeling of active and placebo products was discovered, yet it's unclear if, or to whom, this was reported
• in 1 instance of mislabeling, the researcher investigated by looking at the pills
• investigators signed a clinical trial agreement prohibiting them from disclosing information to the FDA without permission from the sponsor
• investigators refused to disclose data to FDA from research supported, at least in part, by NIH grants
• the principal investigator in 2 clinical trials was not a physician and had no experience as a principal investigator
• in 2 clinical trials, when the sponsor became annoyed with the only co-investigator who was a physician, they directed the PI to refuse him access to the research subjects and data, yet no replacement physician was approved in his stead
• adverse events were under-reported
• subjects were enrolled despite having medical conditions excluded by the research protocol
• in 1 instance, a subject requiring emergency medical intervention was simply replaced by a healthy subject who completed the trial in his place
• an Oklahoma federal judge nullified a confidentiality agreement when the sponsor-defendant destroyed study data to avoid discovery in tort action

What's the answer? Accountability.

We believe the way to create a mechanism of accountability is through federal legislation, in the form of a National Human Research Protections Act that would empower the federal government to impose civil and criminal penalties on researchers and institutions that violate established guidelines for the ethical conduct of research on human subjects.

Index of Ephedra Material

Ephedra Research I – FDA and HHS Documents, including:

• FDA Dockets, including industry/sponsor submissions of research allegedly supporting the safety and efficacy of ephedra, investigator submissions allegedly supporting the safety and efficacy of ephedra, trial deposition of Carol Boozer, DsC, principal investigator in two clinical trials of ephedra, FDA Adverse Event Report documents from users of ephedra, and more
• Study commissioned by FDA/HHS on adverse events from ephedra use
• Transcripts of hearings held by HHS on the safety of ephedra
• Clinical research *concept* cleared by NCCAM/NIH for case-controlled study of adverse events from ephedra in adolescents

Ephedra Research II – Clinical Trials Testing Ephedra, including:

• Links to the full-text version of seven clinical trials, study abstracts presented at conferences, meta-analyses, and survey articles
• Peer reviews and subsequent rejection of study by D Kalman from the Journal of Obesity
• Correspondence to the editor of the International Journal of Obesity Research regarding change of published conclusions due to reporting of adverse events

Ephedra Research III – Government Hearings and Investigations, including:

• House Committee on Energy and Commerce, Issues Relating to Ephedra-Containing Dietary Supplements, 23/24 July 2003
• Extensive links to documents made public by the committee including: internal sponsor correspondence, sponsor-investigator correspondence, and FDA memoranda and internal correspondence.
• Committee for Oversight of Government Management, Restructuring, and the District of Columbia, Ephedra: Who Is Protecting the American Consumers? October 8, 2002
• Additional government hearings covering research on ephedra and dietary supplements

Ephedra Research IV – Dubious Research, including:

• FDA Draft Guidance on Use of Material From Deer and Elk in Animal Feed
• Clinical Trials with Elk Velvet Antler
• Clinical Trial conducted by Brian D. Fisher, Ph.D., Faculty of Physical Education and Sports Studies, University of Alberta
• University of Alberta repudiation of results of Fisher
• Lawsuit related to Fisher's clinical trial
• Clinical Trials with Elk Velvet Antler conducted by the University of Calgary (2002-2004)
• Clinical Trial with Elk Velvet Antler currently being conducted by the University of Alberta
• Lawsuits Related to Ephedra
• Media Articles
• Lobbying

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Last Updated: 2007-06-01

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