Download Bio-identical Hormone Therapy: What`s the Harm?

Bio-identical Hormone
Therapy: What’s the Harm?
Bruce Patsner, M.D., J.D.
Professor, Health Law & Policy Institute,
University of Houston Law Center
NAMS Annual Meeting September 26, 2008
Disclaimer
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The views expressed in this presentation are
those of the author only. All information is in
the public domain.
My views do not represent those of the
University of Houston Law Center, The United
States Food and Drug Administration, or any
other government employee
Putting Bio-identical Hormone
Therapy (BHT) in Perspective
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BHT is a major issue at NAMS and every
ACOG meeting every year
There is NO WAY to talk about this
subject without talking about the
medical profession itself
Are there “problems” with BHT?
If so, what are the solutions?
Some Basic Definitions
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Bio-identical – no set definition
Natural – neither artificial nor
pathologic
Pharmacy compounding – defined by
both FDA and Pharmacy industry; at
core is the “triad” relationship
New drug – defined by 1938 FDCA
What Are Bio-identicals?
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Not a scientific term, and no uniform definition in any
medical dictionary
Molecularly very similar or identical to endogenous
hormones; plant-derived from soybean or yam
“Individualized exact doses” to replicate homeostatic
hormone levels of Estrogen, Progesterone,
Testosterone
Dosage is adjusted according to salivary or blood
hormone levels, unlike commercial HR which is
adjusted based on symptom relief
Purported anti-aging, sexual vibrancy and energizing
effects are similar to structure/function claims made
for dietary supplements rather than disease
treatment/prevention claims made for drugs
Some Basic Facts First
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Pharmacy compounding of BHT is now a
multi-billion dollar a year industry
Bio-identical HR drugs are prescription drugs,
not over-the-counter. Physicians are (or
should be) always part of triad.
Absent active participation by the medical
profession, this industry could not prosper or
function the way it has
FDA has been fighting for decades over
whether it has jurisdiction over pharmacy
compounding at all, and to what degree
Why the Surge in Prescriptions for
Bio-identicals from Patient POV?
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Response to widely publicized results from 2002 WHI
Suspicion of traditional medicine
Dislike of big Pharmaceutical companies
Perception it’s a safer alternative
Natural is equated with safer
Wider and more aggressive advertising, via internet
and other media
Patient preference for alternative medicine. Begs
question of just how “alternative” it is
Least likely reason – patients still symptomatic on
properly prescribed commercial HR products
Facts to Frame the Harm Q…
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Little or no substantive data comparing BHT
with commercial HT. The studies all have
deficiencies
Given uncertainty over whether FDA really
can regulate, no real incentive on the supply
side for anyone to do randomized, controlled
or comparative studies it would be great if
someone did
Almost all potential patients could obtain
adequate medical therapy/symptom relief
with commercial HR were they prescribed
properly and patients so inclined to take them
The Problems with BHT
No tested in good clinical trials, and no endometrial
safety data
 “Natural” does not really equal “safer”
 No clinician or patient package inserts documenting
safety/efficacy, and no black box warnings
 No uniform manufacturing standards. In one study
25% of compounded products tested failed quality
control testing vs. 2% of commercially manufactured
drug products
 No formal review of accuracy of advertised claims
This is A LOT of “Nots”. Will it even matter to those
determined to take these products?
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There Would Be No Harm If
the Following Were All True
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Patients fully informed of true risks/safety
Physicians fully aware of limitations on safety/efficacy
data
All advertising of risks/benefits is completely truthful
The pharmacies all product a consistent, excellent
product and did not attempt to practice medicine
All prescriptions were completely legitimate
Salivary hormones levels actually meant something
and were inexpensive to boot
BHT were proven as safe and effective as other HR
FDA found more important things to regulate
What Harm/Potential Harms,
and Harm to Whom?
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To patients?
To prescribing physicians?
To medical societies?
To the medical profession?
To commercial drug manufacturers?
To compounding pharmacies and their
industry?
To regulatory agencies such as FDA and state
pharmacy/medical boards?
To the reputation of our federal courts?
Discuss Data Before Harms:
Likely Bottom Lines
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BHT may be just as effective as commercial
HR, and likely is so though never proven to
be
BHT never been shown to be safer or more
effective
BHT should be just as safe as commercial HR,
but there’s no reason for it to be any safer
than any other HR
If all this is true, why are physicians writing
so many prescriptions? Because medicine is
more than an art, it’s also a trade/business
Summary of Recent Literature
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Cirigliano M. Bioidentical Hormone Therapy: A Review
of the Evidence. J. Women’s Health 16: 2007
Moskowitz D. A Comprehensive Review of the Safety
and Efficacy of Bioidentical Hormones for the
Management of Menopause and Related Health
Risks. Alternative Medicine Review 2006
Fugh-Berman A et al. Bioidentical Hormones for
Menopausal Hormone Therapy: Variation on a
Theme. J. Gen. Internal Med. 22: 2007. This one
points out that use of salivary hormone levels may
result in use of doses that are higher than the least
effective dose (LED), an approach favored by both
medical societies and FDA Guidance Documents.
Practices Which Don’t Measure Up
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The salivary hormone level thing. Let’s call it
friendo – this is junk medicine
Promoting BHT as safer, more effective, or
cancer-preventive
Promoting BHT as a wholesale replacement
for commercial HR products. This is not
compounding.
Not taking enforcement actions against those
pharmacies which are the biggest offenders
State boards not pursuing fraudulent activity
How Do Some Compounding
Pharmacies Hurt Patients?
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“practice medicine” by adjusting doses of BHT independent of
physicians.
Note: something is needed to adjust doses in order to claim that
the therapy is individualized
Promote these products globally to any patient as a replacement
for commercial HR products which are safe and effective for
most patients
Make false claims regarding safety/efficacy
Overcharge for these meds?
Largest compounding pharmacies just drug manufacturers in
disguise
Continued litigation by some pharmacies over 1st amendment
issues now runs risk of eliminating availability of compounded
drugs for many patients
How Do Physicians Hurt
Patients?
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By taking patients off meds with known
safety and efficacy profiles to place them on
BHT where these are unknown
Waste scarce patient financial resources on
meaningless hormone level testing and more
expensive BHT that offers no therapeutic
advantage.
Just because patients want it and are willing
to pay for it does not mean you have to go
along with it. How about medical decision
making – prescribe only when it’s indicated
How Can Federal Courts Hurt
Patients?
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By holding that all compounded prescription drugs
are new drugs, as defined by the 1938 FDCA
In the long run this could restrict availability of many
kinds of compounded prescription drug products
Could theoretically require pharmacies to do clinical
trial to support an NDA to meet new drug approval
requirements
Could force pharmacies into doing IND applications in
order to demonstrate that they are planning on
submitting an NDA.
No pharmacy can really afford to do either of these
Update on Federal Litigation
Over Pharmacy Compounding
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Historically most drugs were compounded drugs; now only 8%
FDA originally considered all compounded drugs to be new
drugs, but left much of this practice alone and intent only to
intervene when pharmacies were manufacturing, not
compounding
1997: FDAMA abandons FDA’s long-standing position on
compounding but creates bigger problems with FDA’s attempt to
restrict promotion of specific compounded products, as opposed
to pharmacies just advertising that they compound
Results in Western States litigation which FDA loses
FDA then back to “enforcement discretion” approach to
selectively intervene; pharmacy industry still takes position
compounding is integral part of normal practice of pharmacy
and none of FDA’s business
The problem is the litigation doesn’t stop
Most Recent Federal Court Decision
Continues to Create Problems
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Med Ctr Pharm v. Gonzales (W.D. Tex 2006) – holds
compounded drugs are not “new drugs” in a bench trial. FDA
loses, but appeals
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Med Ctr Pharm v. Mukasey (5th Circuit 2008) reverses but
muddies the waters
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Compounded drugs ARE new drugs and FDA can regulate,
BUT
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Congress did not intend to deem all compounded drugs new
drugs, and
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Disagrees with 9th Circuit and holds that §503A of FDAMA
does remain in effect (even FDA had agreed it was no longer
in effect) and that the advertising restriction sub-section
could be split off from the rest of the section (something the
9th Circuit said could not be done) and that alone was invalid
All of this leaves us where, exactly? Confused yet? They are…
Medical Center Pharmacy v.
Mukasey (5th Circuit 2008)
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Importance relates to Section 503A of FDCA
In the 9th Circuit territory (California, Nevada, Arizona, Oregon,
Washington) pharmacists cannot claim protection of this section
(under FDAMA FDA ceded jurisdiction over compounding to the
states), whereas they can in 5th Circuit
Status of all of this in the rest of the U.S. now uncertain
because of split in Appellate Courts
These cases not originally driven by FDA but rather by
compounding pharmacies who claimed FDA attempts to restrict
their advertising of specific compounded drug products violated
their commercial speech rights under the 1st amendment
The problem is that they have now jeopardized all of pharmacy
compounding because this will likely go up to the Supreme
Court and how they will decide is not known.
This was not the case when I talked at NAMS on this in 2006
Implications: if compounded
drugs are “new drugs” by ruling
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FDA has real jurisdiction over all of it
If sold compounded drug not supported by an approved NDA
can either be seized or pharmacy enjoined from making and
selling. End result: some patients won’t get these meds
No pharmacy has $800K lying around to invest in an NDA
application or the millions it will take to do clinical trials to prove
they are safe and effective
Pharmacy compounding could cease to exist
FDA will likely “selectively enforce” to prevent this, and the
whole litigation cycle will start all over again since enforcement
criteria will be somewhat arbitrary (i.e. if you’re making too
much then you are a manufacturer, not a traditional
compounding pharmacy)
Enough about Judicial Harm.
Can Patients Hurt Themselves?
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Patients have this right. Physicians do not.
Patients can, and do, ask for medications and
procedures that are either worthless, harmful, or
frivolous. Look at dietary supplements, plastic
surgery, and C-Section on demand.
It is the medical profession’s job to place real limits
on this. It is our fiduciary duty to do so.
Also, it’s bad enough when patient’s waste their own
money. Indirectly, they are wasting others’ as well
The tradeoff: patient autonomy vs. evidence based
medicine. What do we stand for as a profession,
really?
A final harm: Medical
Information via the Internet
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It’s totally unregulated
FDA has not even begun to really engage this issue,
nor has the medical profession (or anyone else) really
Supreme Court takes the position that information is
better than restriction of information
Lots of horribly false or misleading info out there; the
latter is ok according to courts if there is a disclaimer
even though evidence strongly suggests these are
worthless
BUT, this is also an opportunity for medicine –
medical societies, our profession – to seize the
initiative and assert some good information control.
What Must the Pharmacy
Profession Do to Help Itself?
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Better self-regulation so the feds and
state boards don’t step in
Get rid of false and misleading
advertising
Reign in the worst offenders; they are
ruining it for everyone else. It’s no
different than the Ephedra/dietary
supplement debacle
What Must Medicine Do, or Try
to Do, To Correct Itself?
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Real effort at self-regulation. A license to practice
medicine is not a license to practice junk medicine
Make a determined effort to do the comparative trials
to evaluate BHT claims
Medical societies should consider issuing opinions
about setting limits on patient demands. We are not
selling pizza.
Full disclosure to patients of your financial
investments in labs and pharmacies wrapped up in
the BHT process
As for the physicians who genuinely believe
everything that’s out there about BHT as well as the
pseudoscience behind salivary hormone levels, I’m
not sure what we can do about this
What Must Federal Courts Do?
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Sigh…
It’s always a thrill when federal courts weigh
in on medical matters. Between abortion and
autism, there’s no telling where things are
headed (and that’s just the a’s…)
It is possible the status of pharmacy
compounding will now end up in front of the
Supreme Court. If it does not, we’ll have
different regulatory systems in different parts
of the U.S.
What Should State Boards Do?
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Protect their citizens by taking
enforcement actions against marginal
and fraudulent medical and pharmacy
practices
Police fraudulent claims in ads
The First Amendment offers no
protection for lies
This is Not Just a U.S. Issue
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The health issues are a potential problem for
all countries in North America even if the
costs of compounded BHT and the manner in
which the government regulates them is not.
I’m open to suggestions from members of
NAMS outside the U.S. on how to approach
this issue
Summing Up the Harms
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Economic (for patients)
Patient Safety (for patients). Need data
Regulatory – for government and
courts. The latter are confused, and
confusing.
FDA – what’s the point if you’re only
going after the small fish?
Reputation – for medical profession
Where We Are Likely Headed
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A U.S. Supreme Court decision to resolve the issue
Compounding pharmacies will try to stay under the
radar screen if they are smart, but it may be too late
because of continued litigation in federal court
Medical societies such as NAMS will continue to do
the correct thing by continuing physician and patient
education. Perhaps more of an internet presence with
very attractive, and the best, websites.
Medical profession self-regulating: don’t count on it,
but greater effort to kill medicine with no good
evidentiary basis would be a nice start
Thank You
“Qui tacet consentire videtur”*
He who is silent is taken to agree