From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 23 Sep 2005 21:39:47 -0700
Message-ID: <1127536787.611915.98790@g43g2000cwa.googlegroups.com>

fresh~horses wrote:
> Last month:
> The head of the Agency of Women's Health at the FDA, Dr. Susan Wood,
> resigned over the FDA's refusal to make the morning after pill OTC.
> http://www.washingtonpost.com/wp-dyn/content/article/2005/08/31/AR2005083101271.ht
>
>
>
> Last week:
> The FDA appointed a male veterinarian as acting director to fill Dr.
> Susan Wood's position. Then, after flack from women's groups, they
> unappointed him and denied they'd ever appointed him but... .
> http://www.tompaine.com/print/fda_shenanigans.php
> (follow links within)
>
>
>
> Today:
> The brand new still-wet-behind-the-ears head of the FDA abruptly
> resigned.
> http://nytimes.com/2005/09/24/politics/24fda.html
>
>
>
> It was the best of times. It was the worst of times.


COMMENT:

It was the dumbest of times. The FDA's OTC regulatory and application
policies resulted in a situation where, for nearly two decades, the
only safe non-drowsiness producing antihistamine was only by
prescription, not OTC. While meanwhile we struggled along with OTC
antihistamines that put people to sleep at the wheel, and other
prescription antihistamines that were still sedating or (even worse)
lethal causes of heart arrhythymias. This situation was so bad it
finally got to the point that one HMO company (Wellpoint) actually
petitioned the FDA to make ANOTHER company's drug available OTC.

Don't get your knickers in a twist thinking the recent FDA
foot-dragging might be some kind anti-female agenda. You're not being
singled out. The FDA has an effective anti-human agenda-- it's just
that this time women happen to be the segment of humans bearing the
regulatory problems. Never explain with complex politics and trickery
and bigotry what can more adequately be explained by simply
bureaucratic intertia, sloth, and simple stupidity. There's plenty of
the last to go around at the FDA.

SBH

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: Sat, 24 Sep 2005 09:18:20 -0400
Message-ID: <dh3jna$ih2$1@reader1.panix.com>

Steve Harris wrote:
> regulatory problems. Never explain with complex politics and trickery
> and bigotry what can more adequately be explained by simply
> bureaucratic intertia, sloth, and simple stupidity. There's plenty of
> the last to go around at the FDA.

While I agree with this general sentiment, my impression from various
news reports is that the FDAs decision on Plan B had more to do with
"complex politics" than with "bureaucratic inertia".

--
David Rind
drind@caregroup.harvard.edu

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 24 Sep 2005 19:16:45 -0700
Message-ID: <1127614605.207105.233420@o13g2000cwo.googlegroups.com>

David Rind wrote:
> Steve Harris wrote:
> > regulatory problems. Never explain with complex politics and trickery
> > and bigotry what can more adequately be explained by simply
> > bureaucratic intertia, sloth, and simple stupidity. There's plenty of
> > the last to go around at the FDA.
>
> While I agree with this general sentiment, my impression from various
> news reports is that the FDAs decision on Plan B had more to do with
> "complex politics" than with "bureaucratic inertia".
>
> --
> David Rind
> drind@caregroup.harvard.edu


Complex politics there may have been, and may still be, but you don't
need them to explain the status quo. The point is that what was being
attempted was to overcome plain old bureaucratic inertia. For an agency
stuffy enough to keep claritin and nicorette off OTC status (which they
should have been granted in review, the moment they were approved to
sell at all) I think it's more than naive to imagine that the FDA would
just roll over and allow OTC abortifacients. I mean, come ON.  It will
eventually happen, but not today and not tomorrow. You'll see OTC SSRIs
first (that would be fluoxitine or citralopram). Every one of these
drug classes takes getting used to, before society tolerates them. Just
as with OTC H2 blockers and OTC proton pump inhibitors. The whole
process reminds me of a much of baboons poking at a dead snake. One day
we'll see an OTC blood pressure pill (my guess is captopril). But not
today, and not tomorrow. The head of the FDA could resign over it, and
you still wouldn't see it soon. Things just don't work that way, at
that agency.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 24 Sep 2005 23:05:20 -0700
Message-ID: <1127628320.673299.322640@g49g2000cwa.googlegroups.com>

SJ Doc wrote:
> At the time low-dose ibuprofen (as Advil) went over-the-counter
> (OTC), a nephrologist friend of mine shook his head and predicted
> an enormous increase in patients predisposed to chronic kidney
> disease (CKD) progressing to Stage 5 and life on dialysis.  He
> was pretty much right.  The indiscriminate use of any medication -
> Rx or OTC - has adverse consequences.


Hmmm. I'll take your word for it. Last I looked, the NSAID effect on
renal function was thought to be generally temporary and reversable,
and chonic renal failure was not clearly related to lifetime NSAID use.
There have been a few case-control studies that suggest it, but just as
many that do not. There's a good review by McLaughlin:

http://dceg.cancer.gov/pdfs/mclaughlin546791998.pdf

There is also some good evidence for phenacitin and and its metabolite
APAP causing renal failure over a lifetime, but of course APAP/Tylenol
has been OTC since 1955.


> But I think you're entirely wrong about the degree to which the
> officers of the FDA have the lawful power to compel a manufacturer
> to make a product available OTC if that manufacturer doesn't desire
> to do so.

COMMENT:
Sorry, but YOU are wrong. The OTC vs Rx decision is entirely at the
pleasure of the government. And we are talking about an exact case
where the company was basically forced into OTC status, with
loratadine. True, FDA hasn't forced Zyrtec into OTC status dispite
Wellpoint's application, so yes, it can be a battle. On the other hand,
Zyrtec can be a bit sedating. Fexofenidine's license is up, and the FDA
has okayed OTC status there. A generic OTC fexofenidine is a done deal,
if it hasn't happened already.

>  The last time I looked, a patented product was the exclu-
> sive property of the patent's owner.

COMMENT:
Sure, but that has nothing whatsoever to do with whether or not it's
sold OTC, by Rx, or is added as a controlled substance regulated also
by the DEA.


> With regard to medicinal
> products, the enabling legislation authorizing the FDA's actions
> require them to receive from a patent holder a series of submission
> documents leading up to a completed new drug application (NDA),
> which outlines the purposes for which the patent holder is seeking
> FDA marketing approval.
>
> If the patent holder wants the drug to be marketed as a prescription-
> only product, they'll say that in the application process.  If they
> want to be able to sell it OTC, they'll say *that*.


COMMENT:
So they will. But there's absolutely nothing to say the FDA needs to
respect the company's desires on the matter. About the only say the
company really has is whether or not to market the product at all. They
can refuse, if they like. But if the FDA decides it's an OTC product,
the manufacturer can't do much but squawk.



>  The FDA has
> the duty to evaluate that request, and if the FDA's advisors and
> administrators determine that a request for OTC marketing is in-
> appropriate (and you honestly think that captopril [Capoten, old
> Squibb, now Bristol-Meyers Squibb] ought to go OTC?), they'll
> disapprove the application.

COMMENT:
Yep. But the reverse also happens, and somebody can make your
application FOR you. The FDA is set up for maximal laziness. Just as
with GRAS applications, they now make the applicant do almost ALL the
work. I'm amazed the FDA still does anything at all when it comes to
drugs, but I suppose
they have to look like they're doing something, for congress (and to
justify those exorbitant NDA fees). When it comes to GRAS petitions,
FDA really actually DO do nothing but post GRAS petitions, and often
just let them sit there, for public comment. Forever, without need for
formal FDA ruling. They'd like that to be the full regulatory extent of
it, but since they proposed the messy "regulation without rulings" idea
in 1997, even that is stuck in limbo. What a mess.


> I'm not saying that the FDA serves a beneficial purpose, or even
> that the enabling legislation under which the FDA operates is in
> any way constitutional.  Clearly, it's not.  But the statutes do not
> even begin to empower the FDA's Vogon bureaucrats to tell a
> patent holder what said property owner *must* do with the
> goods in his/her keeping.  If the patent holder of a particular
> pharmaceutical product doesn't want to have his/her intellectual
> property sold over-the-counter, he/she is perfectly free to with-
> hold it from that segment of the world market that is under the
> unconstitutional control of the FDA.

COMMENT:
Yes, as noted, if they don't want it sold OTC in the US, the only thing
they CAN do is refuse to sell it in the US at all, even as
prescription. But they cannot chose under what status to sell it in the
US, if they do decide to sell it in the US.



> And if the FDA won't approve the marketing of a patent holder's
>  product within the FDA's statutory but constitutionally illegiti-
> mate jurisdiction, the manufacturer is perfectly free to sell it else-
> where.

COMMENT:
Sure, so long as they make it elsewhere. Or else make it in the US by
cGMP for export-only.


> Note that sanofi (now sanofi-aventis) peddles a second-
> generation "atypical" antipsychotic drug called amisulpride (trade-
> marked as Solian in several countries) just about everywhere in
> the world other than in these United States.  To the best of my
> knowledge, they've never even waved the molecule under the
> noses of the boys down in Rockville.

COMMENT:
Yep. The company doesn't have to sell in the US at all if they don't
want to.


> And the FDA did not "keep claritin and nicorette off OTC
> status" at all.  While Claritin (loratadine) was under patent,
> Schering Plough did its very damnedest to maintain its
> status as a prescription drug.

COMMENT:

Well, if you call simply doing nothing, "their very damnedest." As you
know, if you do nothing, the FDA will also do nothing. The circus for
Claritin came when somebody (Wellpoint) filed the FDA OTC petition FOR
Schering. They fought that for about 2 weeks, until they couldn't keep
a straight face, and then they gave in and joined Wellpoint's petition.


> The same goes for the patent
> holders of Nicorette gum (SmithKline, now GlaxoSmithKline),
> who kept it as a prescription-only product until it had neared
> the end of patent exclusivity in 1996, whereupon they took the
> product OTC in exchange for a three-year extension of market-
> ing exclusivity (i.e., an effective extension of the product's
> patent life) while conducting pharmacovigilance studies on the
> product's safe use under OTC access.

COMMENT:

I don't know who owned the original patent on the gum delivery system
(the only thing patentable, of course) but it must have originally been
Marion Merrill Dow, since they actually brought out the first nicotene
gum (SK came in later and Hoechst bought out Dow). But no, this
couldn't be nearing the end of patent life, since the gum hit the US
market in 1984, so 1996 is only 12 years from there. The standard then
was 17 years from launch date, so I imagine that SK/Hoechst must have
jumped the gun and applied for OTC in 1996, many years before their
exact gum-delivery system went off patent.

The cat was out of the bag in 1996 on OTC nicotene anyway, since two
nicotene patches were OTCed the same year--- not only SK's NicoDerm but
also a competitor (Pharmacia-UpJohn's NicoTrol, which actually beat
them to OTC). So I suspect the patch OTC had something to do with the
gum going OTC about the same time, not pending loss of patent.  As the
FDA is lazy, you may be right that they traded SK 3 years of OTC gum
exclusivity for post marketing survailance. However the patch, which
had been by Rx for less than 5 years before it went OTC, got NO post
marketing survailance, so that was hardly a standard. The patchmakers
were in no position to dicker, as you say, since there were 4 patches
but still only one gum. In general, OTC products get no survailance
after they go OTC. And, as noted, the 4 Rx nicotene patch products got
< 5 years of Rx status before 2 of them suddenly became OTC
competitors, one having forced the other (I don't know which forced
which). So generally you cannot use any of these as arguments for how
things "usually" happen. Politics and the FDA do as they please on
these issues. Though, as noted, the companies usually are the driving
forces to get things OTC.


> Schering Plough could not manage such a dicker with their
> loratadine products (they'd spent years proving that Claritin
> - although a pretty weak and commonly ineffective antihista-
> mine - *is* astonishingly safe), and so the rug came out from
> under Kogan and Kenilworth when the patent life of Schering
> Plough's "blockbuster" drug died an ignominious but perfectly
> anticipatable death a few years ago.

Yep. As discussed in another message. BTW, Wellpoint, the HMO you
complained about, did end up giving their members coupons to buy
generic loratadine. So they did get it anyway.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 24 Sep 2005 20:23:17 -0700
Message-ID: <1127618597.348030.126080@g47g2000cwa.googlegroups.com>

SJ Doc wrote:
> On 23 Sep 2005 21:39:47 -0700, Steve Harris wrote:
>
> >It was the dumbest of times. The FDA's OTC regulatory and application
> >policies resulted in a situation where, for nearly two decades, the
> >only safe non-drowsiness producing antihistamine was only by
> >prescription, not OTC. While meanwhile we struggled along with OTC
> >antihistamines that put people to sleep at the wheel, and other
> >prescription antihistamines that were still sedating or (even worse)
> >lethal causes of heart arrhythymias. This situation was so bad it
> >finally got to the point that one HMO company (Wellpoint) actually
> >petitioned the FDA to make ANOTHER company's drug available OTC.
>
> Wellpoint is not a drug manufacturer.  Wellpoint is not an "applicant"
> in the FDA regulatory sense of holding an approved New Drug
> Application (NDA), and therefore responsibility for complying with
> FDA regs (Title 21, U.S. Code of Federal Regulations) in the way
> a pharmaceutical product's manufacturer (either innovator or generic)
> must.  Wellpoint is just another Mangled Care [or is that "Managed
> Money"?] Organization (MCO).


COMMENT:

I *said* Wellpoint was an HMO. Please see above. They didn't *need* to
be an "applicant" in the sense of NDA application, to petition the FDA
to switch the legal status of a drug. Anybody can petition the FDA for
such changes, and although it's unusual for the maker not to be the
petitioner, it's completely within the law (the right to petition the
government on various regulatory matters is pretty high up there, in
terms of rights of citizens, don't you know. See Bill of Rights). Such
a petition forces the FDA to consider the safety issue, and so it did.


> Wellpoint's effort was entirely self-serving.  If I remember aright,
> Wellpoint's petition covered all of the "second-generation" prescrip-
> tion antihistamines (including desloratadine) but not in order to
> improve OTC access to less sedating medications.  They wanted
> to be able to stop paying for drugs like Zyrtec, Allergan, and
> Clarinex under the prescription benefits plans for which Wellpoint
> was receiving hefty payments from Wellpoint's clients.  Third-party
> "health insurance" payers almost never have any obligation whatsoever
> to cover the costs of any *non*-prescription medications (even, for
> example, aspirin taken under the explicit direction of a physician)
> and *that* was Wellpoint's true motivation.


COMMENT:

Wellpoint never said otherwise! They said they were tired of paying a
lot of money for non-sedating antihistamines, and they said that the
average American should be just as tired of it, if they didn't happen
to have a health plan that covered all prescriptions. And they were
right. These things were going for $3 a pill. This was one of those
cases where the HMO's interests coincided with the public's interests
(I'm speaking of the case of Claritin, which was at that time just
going generic--- even though yes indeed, Wellpoint petitioned for the
feds to make Zyrtec and Allegra OTC as well, which had a lot of patent
time still to run).


> The fact that you and I might agree with the contention that
> drugs like cetirizine and fexofenadine are even more appropriate
> candidates for OTC sales than are "first-generation" antihistamines
> like diphenhydramine (Benadryl) and chlorpheniramine maleate
> (Chlor-Trimeton) has nothing to do with what those penny-
> pinching bastards at Wellpoint were trying to diddle their clients
> out of.


COMMENT:

The question of just who was diddling who here, needs examining. As
noted, at the time, Claritin was just going off patent, but was still
selling as the branded drug at $3 a pill in the US (yes it was-- I was
THERE).  In Canada, Schering-Plough had been selling it OTC for 12
years, and it was going for 40 cents a pill; same exact drug. Now, who
was getting screwed?

Wellpoint "well-pointed out" that only the prescription status of the
drug in the US allowed that kind of economic insulation against
re-importation (re-importatation laws don't work the same for Rx
drugs). Meanwhile, everybody in the US had to pay the extra $2.50 a day
if they didn't want to fall asleep when taking these drugs. I'm sure
that killed a few people. When people were fully insured and the doctor
wrote them a scrip for Claritin, the insurers had to pay that extra, to
be sure. But in the end, it's always the consumer who pays one way or
the other, no? If the drug company gets an extra $2.50 a pill in the
US, that comes out of the consummer's pocket, sooner or later. If
later, as greater insurance premiums. There's just no way to somehow
make insurance companies absorb it. That's the whole POINT of how
insurance companies operate.

Duh, do I have to explain this in detail??

In any case, during the FDA trials Schering-Plough did some mumbling
about complex safety issues being involved, all the while knowing (and
hoping nobody else would find out) that they'd been selling it OTC to
Canadians for a dozen years for about a seventh of the price. I suppose
Canadian safety just isn't as complex, eh?

In any event, Schering finally gave up and (I think in "scher"
embarrassment as much as anything else) joined the petition to the FDA
on Wellpoint's side.

And that's the story of how you got branded Claritin at 20 cents a
pill, which is the price today in the US on-line. And 10 cents for
generic. Instead of $3. Comprende?

Now, at this point somebody is going to ask me if I don't support
Schering-Plough being able to make as much as the market will bear from
a non-sedating and better antihistamine, while their patent ran on it.
Answer: you bet! If you're a drug company, charge what the market will
bear on your inventions! Just don't try to dishonestly diddle with the
regulatory laws and treat it as a "safety issue" to protect your price
diffefential from re-import errosion, when you try to sell at
differential prices, at home and abroad. If you want honest business
tarrifs as a way toward protectionism for your product, then have the
honesty to try to argue for those. Some industries actually get away
with doing that. But don't try to medicalize the safety issues, and lie
your way into tarrifs on the back of US drug paranoia. Untruth, as
usual, just hurts everybody.

In any case, to sum up, there's no doubt that Wellpoint was acting in
its own self-interests. But they were completely up-front and open and
honest about it, and made the argument successfully that their
interests were also YOURS and MINE. (As patient and doctor).  It's
Schering-Plough that comes out the villain of the antihistamine story.
And there only for their dishonesty. If they'd sold Claritin for $3 a
pill OTC both in the US and Canada, and never said boo about the safety
issue (except to point out truely that their drug is safer than the
first gen antihistamines), I'd have no problem with them at all. As it
was, they stressed the safety of Claritin in their advertizing, saying
it couldn't be told from sugar pill (which is true). But they only said
that when it was in their interests, and when it came to market
protectionism, they basically lied. Eventually, it caught up with them.


Wellpoint helped get out the truth. I didn't know why you're not
happier with an honest HMO which, in the process of doing themselves a
favor, also did you a favor. Wellpoint didn't HAVE to do what they did.
They could simply have jacked up their premiums, knowing they were
competing with US HMOs who had no choice but to do the same. Instead,
they figured they'd instead help out the regulatory process to do what
it should have been doing all along. Which is to get safe drugs OTC,
ASAP.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 26 Sep 2005 00:08:49 -0700
Message-ID: <1127718529.177671.225820@g44g2000cwa.googlegroups.com>

SJ Doc wrote:


> Title 21 of the U.S. Code of Federal Regulations is available online
> at:  http://www.access.gpo.gov/cgi-bin/cfrassemble.cgi?title=200221
> Could you please provide a reference from that or some similar
> source to prove your contention regarding the "OTC vs Rx
> decision"?  I don't doubt your good faith, but I have trepidations
> about the accuracy of your knowledge.

COMMENT:
Well, then you can check with the pharmacists. See the subheading
"status changes", which is referenced with the legalities.

http://www.uspharmacist.com/index.asp?show=article&page=8_1149.htm

> >COMMENT:
> >
> >Well, if you call simply doing nothing, "their very damnedest." As you
> >know, if you do nothing, the FDA will also do nothing. The circus for
> >Claritin came when somebody (Wellpoint) filed the FDA OTC petition FOR
> >Schering. They fought that for about 2 weeks, until they couldn't keep
> >a straight face, and then they gave in and joined Wellpoint's petition.
>
> When Schering Plough petitioned the FDA for permission
> to take loratadine OTC toward the close of the product's
> patent life, it was not out of embarrassment (pointy-haired
> bosses like Kogan don't *get* embarrassed when you accuse
> them of price-gouging) but rather because they were ready to
> introduce a successor product line - Clarinex (desloratadine,
> licensed from drug developer Sepracor) - to the prescription
> market, and they wanted to cut the legs out from under the
> generics manufacturers who had gotten their own "me-too"
> ANDAs into Rockville well in advance of the Claritin patents'
> expiration.

COMMENT:
And you know this, how?  I'm only making an inference from the
historical record, which is that they fought the switch initially, then
caved. I don't see how that bahavior fits with your inside track.


> The reason why physicians write prescriptions for certain
> medications is that patients' prescription plans will pay for
> those medications.  In most cases, prescription plan co-
> payments (even for "non-preferred" products) are less
> than the costs they would incur were they to purchase an
> OTC alternative.

COMMENT:

This I know. And it's a nasty business. And one that tends to keep the
price of a month's worth of OTC equivalent (if there is one) at roughly
the same price as a month's co-pay for something that is still Rx, no
matter what its "real" price to the insurer. Which is the case with
branded OTC Claritin today. It's no accident it costs what it does,
which is around $10 a month, if you buy it at the drugstore.

And by the way, you'll be glad to know your argument that cost to
consumer *if counted only as copay cost* is (or may be) actually
slightly less for Rx than the OTC product, has been used by makers of
Zyrtec, to try to keep it Rx, on the basis that doing so will benefit
the public. LOL.


>  If there were generic loratadine products
> available only as prescription drugs, there would be little
> reason for doctors to write for Clarinex products.  The
> difference between loratadine and desloratadine from a
> clinical point of view is effectively nil.


Of course. Possibly I missed your point?



> And the patent life of a drug product is decidedly *not* "...17
> years from launch date" but rather 17 years from the date of
> its patent approval.  Which precedes its identification to the
> FDA as a new molecular entity (NME) of therapeutic potential.
> Moreover, the "launch date" for a pharmaceutical product is not
> necessarily the date upon which the FDA approves the patent
> holder's new drug application (NDA).

COMMENT:

As a matter of international harmonization, patents (not just drug
patents) now run 20 years from filing rather than 17 from approval, but
that's relatively new and wouldn't have affected the Nicorette patent.

Nicotine of course would not be a new molecular entity, so this would
not be that kind of a patent. Rather a methods patent on use of
nicotine polacrilex gum for addiction (the original patent on nicotine
in amberlite goes back to 1973). I haven't the patience to look the
original Merrell Dow one up (feel free).

We're both wrong on time-- it's actually 14 years from launch date. I
knew time had been added but missed how much (assuming fairness, LOL).
Basically since 1988 the FDA can add (at its discretion) up to 5 years
exclusivity extension to the patent life of a human drug preparation,
to make up for loss of time in regulatory limbo, so long as total
marketing time (and this IS calculated from launch date) isn't extended
more than a total of 14 years (not 17 years) thereby. See 21 CFR Part
60. From 1984 to 1998 is 14 years, so apparently Nicorette got 2 extra
years by this mechanism. I doubt they got 3, because it's not within
the FDA's power to give them a total of 15, and 3 extra years would
have done just that. Watson got FDA approval for their gum in March 99,
which is LESS than 3 years from Nicorette's OTC date, and I suspect the
extra was just Watson ANDA application time. Short at that; I guess
they didn't file enough ahead.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 26 Sep 2005 01:14:04 -0700
Message-ID: <1127722444.389065.323840@o13g2000cwo.googlegroups.com>

SJ Doc wrote:
> What Wellpoint attempted was an effort to violate the property rights
> of several patent holders.  What if a big retailer like Best Buy were
> to petition a federal agency to impose by fiat some sort of change in
> Apple's marketing plan for their patented iPod product line?  Sure,
> Best Buy has the right to petition government (the full phrases is
> "for redress of grievances," isn't it?).  The question now devolves
> into consideration of private property rights, the appropriate powers
> of civil government, and standing.
>
> In Wellpoint's case, the grievance is: "I want to buy this manufac-
> turer's goods at a cheaper price than the greedy bastard is willing
> to charge!"  In the course of their push to get the Federal govern-
> ment to violate the patent rights of the manufacturers of the "second
> generation" (less-sedating) antihistamines, you say they argued that
> "...the average American should be just as tired of [tired of paying
> a lot of money for non-sedating antihistamines as Wellpoint was],
> if they didn't happen to have a health plan that covered all prescrip-
> tions."
>
> It was hardly a question of concern for people who "...didn't hap-
> pen to have a health plan that covered all prescriptions."  As I'd
> said, Wellpoint had (and still has) a contractual relationship with
> many of its clients to cover the costs of certain prescription drugs.
> That contract doesn't give Wellpoint or its corporate officers any
> standing whatsoever to utter a petition wherein they claim to be
> acting on behalf of the general public - i.e., "...the average Ameri-
> can...[who] didn't happen to have a health plan that covered all
> prescriptions."  And, of course, Wellpoint wasn't.  Their purpose
> was entirely self-dealing.  Wellpoint was taking boatloads of money
> out of the pockets of their clients, and they wanted - quite naturally
> - to keep as much of it as they possibly could.
>
> Do I have to explain this in detail?


COMMENT:

Apparently. I've already referenced the statute under which Wellpoint
acted. It had been used before, in the case of dextromethorphan. But
rarely.

Nobody was trying to take anybody's property away. Wellpoint didn't
(and couldn't) ask for Schering to change its pricing. They would have
been perfectly free to sell it OTC for $3, if they could get it.

Unfortunately, they wouldn't have been able to, because most people
wouldn't pay it, and the remainder would try to get it from Canada (a
practice which would might still be technically be illegal, perhaps,
but the chances of which would go up markedly for an OTC drug.) Or it
might actually be legal. The reimportation safety issue has been for Rx
drugs, not OTC (and has basically been over the fact that the US gov
CAN certify reimported Rx drugs safe, but refuses to). I think an OTC
drug made IN the US for Canadian use could be re-branded in Canada by
somebody (a middleman) and sent right back. As is done in Europe
whenever drug prices get out of line between countries (even for Rx
drugs). But feel free to educate me otherwise, if you can cite law.

Now, is this stealing from the company which is "honestly" trying to
sell its wares OTC in two countries at two very different prices, and
seeking government help to keep nasty free marketeers from buying it
cheap THERE and moving it BACK there to here?  As far as I'm concerned,
once a company sells its wares, the price is out of its hands. The
goods now belong after the sale, to the buyer. Who can re-sell them
elsewhere to buyers who are being pricejacked elsewhere. Is there some
ethical idea you can cite which suggests otherwise?


> The Wellpoint goniffs made this outrageous move at a strategically
> opportune moment, when the first of the safer less-sedating drugs in
> this therapeutic category was approaching the end of its patent life.
> Note that there was nothing in their petition to encourage the FDA
> to grant OTC status to several other prescription drugs in this
> category that were already off-patent.

Such as? Hismanal and Seladane you mean? See below.

We've been over Wellpoint's motives. There's no secret about them.
There was nothing wrong with them. Had they been unsuccessful, as
noted, they would simply have charged their insurees more. You can
change insurance companies, usually twice a year.


> Maunder on all you like about having "...been THERE..." when
> Claritin was selling for $3 a pill (that wasn't the *Redbook* price,
> of course, but you're polemicizing and therefore not expected to
> bother taking into account the uncontrolled mark-ups charged by
> pharmacies at the point of sale), but how much experience have
> you had in prescribing Hismanal (astemizole, Janssen Pharmaceutica)
> or Seldane (terfenadine, Hoechst Marion Roussel) before these two
> supposedly safe "non-sedating antihistamines" - both of which had
> gone successfully through the FDA's and various other national
> governments' approval processes - were pulled off the market in
> the late '90s?



Since I was licensed in 1984, you can imagine the answer: a lot.

Did I kill anybody with arrhythmias?  Not that I know of. That one was
a terribly complex issue, and the "drug interaction" was merely one
that raised blood levels, so it was a dose issue also.



> Did Wellpoint also petition for OTC sales of astemizole and ter-
> fenadine?  Except for certain nasty drug-drug interactions (which
> have been well-defined and can easily be incorporated in product
> labeling), both Hismanal and Seldane were effective low-sedating
> antihistamines.


No, they weren't well-defined, as it turned out. And no, Wellpoint did
not petition for them in 1996, since they both were known to have
problems. Both were exactly the kind of thing you'd like to keep Rx.



>Aspirin and ibuprofen have worse track records
> insofar as drug safety issues go.


That's not a good argument.


>  So why wasn't Wellpoint including
> those older, off-patent drug products in their petition?
>
> Might it have been because there actually *was* a safety issue
> coloring the use of the "non-sedating" antihistamines as a class?


No, but it might have looked that way, if these two had been included.
As it was, they form a group by themselves and there was no reason to
include them, or consider them at the time. The FDA was already warning
docs about them, and certainly was not about to make them OTC.  And of
course as we know, it eventually pulled them after several others came
out.


> And that this issue took a few years to thrash out, during which
> time we discovered a whole lot of patients whose predispositions
> anent life-threatening cardiac re-entrant arrhythmias had not been
> anticipated until they took Seldane?  Retrospectroscopy is a
> great diagnostic procedure, but it's not available IRL.

COMMENT:
Correct, but in this case, everybody was seeing clearly through the
"prospectoscope," and if I understand your argument, it was that
everybody (Wellpoint and the FDA) were doing their jobs at that,
entirely too well, by NOT including petitions for two drugs which were
at the time known to have problems, and eventually (later) were indeed
pulled off market completely.

BOY, there's just no satisfying you, is there?  What the hell is your
beef? If Wellpoint had put Seldane and Hismanal in, you'd be
complaining about THAT.


> Schering Plough *did* charge what the market would bear on
> their Claritin product line.  I didn't write for Claritin all that
> much (as I've said, it's a pretty weak and relatively ineffective
> antihistamine), and I prefer Zyrtec (cetirizine, Pfizer) both for
> its greater potency and for a pharmacokinetic profile that
> predictably apes its precursor drug (Vistaril [hydroxyzine, also
> Pfizer]), which I first learned to employ when I was on clinical
> clerkships in medical school.  But Schering Plough pumped a
> lot of money into marketing the Claritin products, and that had
> an impact on patient demand for Schering Plough's loratadine
> goodies.


There's actually a fair amount of argument on that point. I'll let you
be my guest in looking it all up on medline.  However, I too, learned
to use hydoxyzine, and my considered opinion is 10 mg of it orally (not
a large dose) would be expected to about as sedating as 10 mg of Zyrtec
is. So the idea that all the sedation comes from the prodrug is
probably hooey, and I'll want a direct comparison between low doses of
them both before I believe otherwise. I think it's YOU who've been
taken in by marketing. And yes, at the standard dose, Zyrtec is a
better antihistamine than Claritin, and you pay for it with sedation.
You pick your drug for your patient. Allegra is probably on the whole
the best drug for the activity, but it's also (till recently) by far
the most expensive.


Allergy Asthma Proc. 2000 Jan-Feb;21(1):15-20.

Safety of second generation antihistamines.

Philpot EE.

Hoechst Marion Roussel, Inc., Kansas City, Missouri 64134, USA.

The sedation related to first-generation antihistamine use has been shown
to compromise performance at school and at work, impair driving, and
decrease the ability to handle tasks that require a high degree of
alertness or concentration. Second-generation antihistamines are less
likely to produce sedation. Loratadine, cetirizine, and fexofenadine are
the most commonly prescribed second-generation antihistamines. Many tests
have been conducted to assess the central effects of these three drugs.
Compared with placebo, at recommended doses loratadine is not associated
with performance impairment. Cetirizine, at recommended doses, has been
shown to impair performance and cognition in several studies, although to
a much lesser degree than older antihistamines. Clinical trials show
fexofenadine is nonsedating, even at very high doses; psychomotor and
driving tests reinforce these findings. Loratadine, cetrizine, and
fexofenadine all have excellent safety records. Their cardiovascular
safety has been demonstrated in drug-interaction studies, elevated-dose
studies, and clinical trials. These three antihistamines have also been
shown safe in special populations, including pediatric and elderly
patients.

Publication Types:
    Review
    Review, Tutorial

PMID: 10748947 [PubMed - indexed for MEDLINE]



> Now, the pliability (indeed, the stupidity) of the general public
> has been a thoroughly execrable characteristic of the market-
> place ever since the division-of-labor economy was first con-
> ceived.  We have many wonderful bad examples to take as
> object lessons, and one of them is the witlessness of patients
> who come into doctors' offices and specifically request certain
> prescription drug products.  But "Stupidity cannot be cured
> with money, or through education, or by legislation. Stupidity
> is not a sin, the victim can't help being stupid. But stupidity is
> the only universal capital crime; the sentence is death, there is
> no appeal, and execution is carried out automatically and
> without pity." (Robert A. Heinlein)


Sigh. Nasty old fart, wasn't he?  Wrote juvenile novels less juvenile
than his non-juveniles. I have, alas, read all of Heinlein at one time
or another in my life. And confirmed on reading _Grumbles_ what'd I'd
long suspected-- that I certainly wouldn't have liked him as a human
being.
You're welcome to continue to be a Space Cadet, though (personally, I
liked Have Spacesuit, Will Travel).


>
> I won't go into a detailed discussion at this point about pharma-
> ceuticals pricing in Canada and the whole drug re-importation
> issue except to observe that your na=EFvet=E9 on this subject proves
> that Heinlein's observation about stupidity is still wonderfully
> robust.  You really don't know squat about it, do you?

You forgot to say where it was that I said something that you think was
wrong, and why.

As for what I know about it, keep on and find out.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 26 Sep 2005 01:58:41 -0700
Message-ID: <1127725120.984606.100190@g47g2000cwa.googlegroups.com>

Steve Harris wrote:
 But "Stupidity cannot be cured
> > with money, or through education, or by legislation. Stupidity
> > is not a sin, the victim can't help being stupid. But stupidity is
> > the only universal capital crime; the sentence is death, there is
> > no appeal, and execution is carried out automatically and
> > without pity." (Robert A. Heinlein)
>
>
> Sigh. Nasty old fart, wasn't he?  Wrote juvenile novels less juvenile
> than his non-juveniles.


I can't resist adding that it's Heinlein I think of whenever I hear
that famous Steve Wright line about why he's depressed: "I wrote two
children's books, but not on purpose..."  Well, Heinlein and Hillary
Clinton.

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine
Subject: Re: fun and games at the FDA
Date: 26 Sep 2005 01:42:16 -0700
Message-ID: <1127724136.236019.52600@g43g2000cwa.googlegroups.com>

SJ Doc wrote:

> Where were you when Schering Plough submitted the NDA for
> Claritin, hm?

COMMENT:
Well, it was FDA approved NDA in 1993, so when WAS the US NDA ap
submitted?  Do you know? Where were you? You act like it was at the
FDA, maybe. But I don't think so.


>Recall that I had mentioned several low-sedation
> antihistamines (Hismanal [astemizole, Janssen] and Seldane [ter-
> fenadine, HMR]) that did, indeed, prove to have adverse drug-
> drug interactions such that in terms of both product liability and
> prescriber reluctance to write for these products, the withdrawal
> of FDA marketing approval was merely frosting on the cake in
> the great confectionary story of their demise.
>
> Do you really think that Claritin - as the situation stood at the
> time of Schering Plough's submission of the NDA - could have
> been supported by a GRAS petition ("generally recognized as
> safe") in advance of *any* clinical experience with the molecule
> whatsoever?

COMMENT:

Ah, say what??!

Claritin was first marketed in Belgium Feb, 1988. In Canada, June 88.
Went **OTC** in Canada, December 1989. Where was I then? Cheering the
demise of the Berlin wall! And you're telling us that when
Schering-Plough went to the FDA with their new drug application in 92
or whatever, it would have been in advance of *any* clinical experience
with the molecule whatsoever?  Bull-crap! It was being sold in about 40
other countries around the world by that time! And in most of them OTC.
Sell it someplace where they can't look up history. `Cause I can. And
you should.

SBH