Bioidentical Hormone Therapy: Whats the Harm

1
Bio-identical Hormone Therapy Whats the Harm?

• Bruce Patsner, M.D., J.D.
• Professor, Health Law Policy Institute,
  University of Houston Law Center
• NAMS Annual Meeting September 26, 2008

2
Disclaimer

• 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

3
Putting Bio-identical Hormone Therapy (BHT) in
Perspective

• 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?

4
Some Basic Definitions

• 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

5
What Are Bio-identicals?

• 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

6
Some Basic Facts First

• 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

7
Why the Surge in Prescriptions for Bio-identicals
from Patient POV?

• Response to widely publicized results from 2002
  WHI
• Suspicion of traditional medicine
• Dislike of big Pharmaceutical companies
• Perception its 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

8
Facts to Frame the Harm Q

• 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

9
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?

10
There Would Be No Harm If the Following Were All
True

• 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

11
What Harm/Potential Harms, and Harm to Whom?

• 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?

12
Discuss Data Before Harms Likely Bottom Lines

• 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
  theres 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, its also a trade/business

13
Summary of Recent Literature

• Cirigliano M. Bioidentical Hormone Therapy A
  Review of the Evidence. J. Womens 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.

14
Practices Which Dont Measure Up

• The salivary hormone level thing. Lets 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

15
How Do Some Compounding Pharmacies Hurt Patients?

• 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

16
How Do Physicians Hurt Patients?

• 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 its indicated

17
How Can Federal Courts Hurt Patients?

• 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

18
Update on Federal Litigation Over Pharmacy
Compounding

• 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 FDAs long-standing position
  on compounding but creates bigger problems with
  FDAs 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 FDAs business
• The problem is the litigation doesnt stop

19
Most Recent Federal Court Decision Continues to
Create Problems

• Med Ctr Pharm v. Gonzales (W.D. Tex 2006) holds
  compounded drugs are not new drugs in a bench
  trial. FDA loses, but appeals
• Med Ctr Pharm v. Mukasey (5th Circuit 2008)
  reverses but muddies the waters
• Compounded drugs ARE new drugs and FDA can
  regulate, BUT
• Congress did not intend to deem all compounded
  drugs new drugs, and
• 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

20
Medical Center Pharmacy v. Mukasey (5th Circuit
2008)

• 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

21
Implications if compounded drugs are new drugs
by ruling

• 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 wont 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 youre making too
  much then you are a manufacturer, not a
  traditional compounding pharmacy)

22
Enough about Judicial Harm.Can Patients Hurt
Themselves?

• 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 professions job to place real
  limits on this. It is our fiduciary duty to do
  so.
• Also, its bad enough when patients 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?

23
A final harm Medical Information via the Internet

• Its 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.

24
What Must the Pharmacy Profession Do to Help
Itself?

• Better self-regulation so the feds and state
  boards dont step in
• Get rid of false and misleading advertising
• Reign in the worst offenders they are ruining it
  for everyone else. Its no different than the
  Ephedra/dietary supplement debacle

25
What Must Medicine Do, or Try to Do, To Correct
Itself?

• 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 thats out there about BHT as well as
  the pseudoscience behind salivary hormone levels,
  Im not sure what we can do about this

26
What Must Federal Courts Do?

• Sigh
• Its always a thrill when federal courts weigh in
  on medical matters. Between abortion and autism,
  theres no telling where things are headed (and
  thats just the as)
• It is possible the status of pharmacy compounding
  will now end up in front of the Supreme Court. If
  it does not, well have different regulatory
  systems in different parts of the U.S.

27
What Should State Boards Do?

• 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

28
This is Not Just a U.S. Issue

• 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.
• Im open to suggestions from members of NAMS
  outside the U.S. on how to approach this issue

29
Summing Up the Harms

• Economic (for patients)
• Patient Safety (for patients). Need data
• Regulatory for government and courts. The
  latter are confused, and confusing.
• FDA whats the point if youre only going after
  the small fish?
• Reputation for medical profession

30
Where We Are Likely Headed

• 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 dont count
  on it, but greater effort to kill medicine with
  no good evidentiary basis would be a nice start

31
Thank You

• Qui tacet consentire videtur
• He who is silent is taken to agree