Transcript Ephedra is an

How to Tell the President…
Or At Least the Secretary of HHS
…The 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.
Southern California
Evidence-Based
Practice
Center
Santa Monica
Los Angeles
San Diego
Efficacy and safety of ephedra and
ephedrine for weight loss and athletic
performance. A meta-analysis. JAMA.
2003;289(12)1537-1545.
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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
• Nature’s Nutrition – Formula 1
• Ripped Fuel (Twin Labs), E’ola, 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including unpublished and non-English literature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
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