How to Tell the President Or At Least the Secretary of HHS The Facts About Ephedra

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How to Tell the PresidentOr At Least the
Secretary of HHSThe Facts About Ephedra
Sally C. Morton, RAND Statistics Group
Shekelle PG, Hardy ML, Morton SC, Maglione M,
Mojica WA, Suttorp MJ, Rhodes SL, Jungvig L,
Gagné J. Efficacy and safety of ephedra and
ephedrine for weight loss and athletic
performance. A meta-analysis. JAMA.
2003289(12)1537-1545.
Southern California Evidence-Based Practice
Center
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Ephedra Use in the United States

• Ephedra is an herbal dietary supplement regulated
  under the Dietary Supplement Health and Education
  Act of 1994 (DSHEA)
• Specifically forbids FDA to regulate
• Forbids disease treatment claims
• Places burden of proof for safety on the
  government
• Ephedra is sold as part of many concoctions
• Metabolife 356
• Natures Nutrition Formula 1
• Ripped Fuel (Twin Labs), Eola, Slacker II
• Ephedra industry claims 3 billion servings are
  sold per year

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Ephedra Clinical Efficacy and Side Effects
Project

• Systematic review project conducted at the AHRQ
  Southern California Evidence-Based Practice
  Center
• Conduct comprehensive literature search,
  including unpublished and non-English literature
• Conduct meta-analysis of clinical trial data as
  appropriate to assess efficacy of ephedra for
  weight loss and improved athletic performance
• Examine safety using data from clinical trials,
  published case reports, and FDA and Metabolife
  adverse event databases

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Our Project Had Started in 2001

• June 2002
• Public Citizen asks HHS Secretary to ban ephedra
  as a threat to public health
• HHS Secretary Thompson announces that RAND will
  conduct a comprehensive review of the existing
  science on ephedrine alkaloids
• August 2002
• Ephedra is an imminent hazard Senator
  Durbin
• October 2002
• The results of the RAND review will help FDA's
  scientists to develop future
  regulatory actions on dietary supplements
  containing ephedrine alkaloids.
  FDA Acting Commissioner Crawford

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The Anecdotal Adverse Event

• Baltimore Orioles pitcher Steve Bechler dies on
  February 17, 2003
• Ephedra is implicated
• "This was certainly a preventable death it
  didn't have to occur, this kind of tragedy," said
  Broward County's chief medical examiner (CBS News
  2/18/03).

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Conclusions Of Our Evidence Report Released
2/28/03

• Ephedra does promote short-term weight loss but
  long-term effects are unknown
• Ephedrine plus caffeine does have modest
  short-term effects on athletic performance
• Ephedra does cause some side effects such as
  palpitations and psychiatric symptoms (source
  clinical trial data)
• The sentinel events (e.g., 5 deaths, 5 heart
  attacks, 11 strokes) we identified are a signal
  that ephedra may cause serious adverse events,
  and this effect is biologically plausible
  (source adverse event case report files)

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Limitations of the Analysis

• Clinical trials
• Usual limitations for clinical trial
  meta-analysis
• No deaths or other serious adverse events
  reported but insufficient sample size to detect a
  rate of adverse events smaller than 1 per 1000
• Case reports
• Did not have access to all reports
• Many reports did not contain sufficient
  documentation
• No estimate of the number of people using ephedra
• Study design considered insufficient to warrant
  conclusions regarding causality
• Definitive case-control study needed to assess
  safety

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Federal Government Response (2/28/03)

• HHS Acts to Reduce Potential Risks of Dietary
  Supplements Containing Ephedra, FDA News
• Ban on advertising effects of ephedra on athletic
  performance
• Proposed new warning label for ephedra
• HHS Secretary Thompson says "We want to caution
  all Americans - particularly athletes and those
  who engage in strenuous activities - about using
  dietary supplements that contain ephedra. There
  continue to be serious questions about the risks
  surrounding this particular dietary supplement."
• Congressional Hearings 7/23-24/03 FDA
  Commissioner McClellan says A ban on ephedra use
  is in the range of options we are considering."

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Ephedra Education Council (3/12/03)

• The Rand report confirms that more than 55
  clinical studies support the safety and benefits
  of the Ephedra/caffeine combination, when taken
  as directed by overweight, but otherwise healthy
  individuals. Recently announced efforts by the
  Food and Drug Administration (FDA) to regulate
  Ephedra should consider these studies in the
  agency's final rulemaking decision. Furthermore,
  FDA should also ban irresponsible marketing
  practices, a complete ban on use by minors,
  mandatory strict science-based serving
  recommendations and medical condition warnings
  for the labels of all Ephedra products.
• The Ephedra industry continues to call upon the
  Food and Drug Administration to adopt
  science-based regulations for Ephedra dietary
  supplement products. The industry is committed to
  working with FDA on appropriate measures that
  guarantee continued access for the millions of
  responsible adult Americans who consume these
  products every day for safe and effective weight
  loss."

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How to Tell The Facts

• Focus on a small number of conclusions and
  support with strong analyses
• Promotes short-term weight loss, no long term
  studies, very limited evidence on athletic
  performance
• Does cause some side effects
• Sentinel events are a serious signal but further
  research needed to establish causality

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How to Tell The Facts

• Anticipate
• Who will focus on which conclusions
• The spins from different audiences and in
  multiple directions
• When you speak to journalists, politicians are
  listening
• Beware yet accept better yet use
  the anecdote