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Sbharris[atsign]ix.netcom.com <sbharris@xxxxxxxxxxxxx> wrote on 11 Sep
2005 16:14:52 -0700:
>> Colleen Fuller:
>> A 2002 Cochrane review of the evidence on recombinant human insulin
>> (Richter B, Neises G. 'Human' insulin versus animal insulin in people
>> with diabetes mellitus (Cochrane Review). In: The Cochrane Library,
>> Issue 3, 2002. Oxford: Update Software) found that "At the time of
>> introduction of human insulin, marketing strategies suggested that the
>> lower immunogenicity of human insulin and the anticipated decline in
>> antibody titres would offer a clinical advantage for insulin-treated
>> patients". This appears to have been a "theoretical" advantage, not a
>> real one.
> COMMENT:
> The Cochrane Review's point of view is that the human insulins were
> introduced into the market without adequate long term safety and
> efficacy testing. That's surely a matter of taste.
No. It's a matter of clinical judgement. The difference being that in
matters of taste, yours and mine are just as valid as anybody's.
> But the review's suggestion that it was somehow mere "marketting
> strategies"[!] that "suggested that the lower immunogenicity of human
> insulin and the anticipated decline in antibody titres would offer a
> clinical advantage for insulin-treated patients," is nonsense!
I read that review once. Nowhere do I remember them mentioning
market[t]ing stragies. As for "suggesting" them - Any such suggestion
would have been in the minds of the readers.
> At the time, no endocrinologist (involved in marketing or not) guessed
> otherwise (if you want to argue that, find me the cite). Nor did the
> Cochrane Review suggest (before the fact) that it might not be the
> case. This result took EVERYBODY by surprise: industry, academia,
> practising physicians and patients, alike.
This is the sort of reason why most drugs have to undergo proper testing
before being introduced. Why genetically engineered insulin was allowed
to be an exception is the real mystery.
> It's simply the usual socialist boloney For Cochrane to blame this odd
> outcome and failure to se the future, in retrospect, on some capitalist
> mechanism. Where were the non capitalists of the time, in opposition?
Cochrane restricted its discussion to purely medical and scientific
matters. Nowhere did it mention political matters.
> Recall the days of yore. I was there. The mid 1980's were a time when
> at least 2 injectable protein products (Growth hormone and Hep B
> vaccine) HAD to be switched to genetically engineered products without
> a long and leisurely safety and efficacy comparison trials, because the
> previous products had come from human sources that were no longer
> possible to use, on very short notice (in once case due to CJD, and in
> the other, due to HIV in donor pools). This was NOT a time when any
> serious voices were suggesting that the project to replace animal
> insulin be treated any differently, even though it (in theory and in
> retrospect) could have been done.
I was there too. And my insulin was casually switched over to GE insulin
by my doctor (A GP, not a diabetes specialist of any sort). The new
stuff wasn't as good as the old. Unlike the drugs you are referring to,
the were no pressing reasons to stop using natural insulin.
>> "Human" insulin is not less likely to produce antibodies than pork
>> insulin. We know why those who use pork or beef insulin produce
>> antibodies, but it's not clear to me why antibodies result from the
>> use of an insulin whose molecular structure is identical to the human
>> insulin molecule. Some (Lewontin, eg.) have suggested that the folding
>> and unfolding action that is used to produce the human insulin molecule
>> is responsible for some of allergies and other problems associated with
>> the resulting insulin.
Quite likely, the "human" insulin molecule is not identical to the human
insulin molicule at all; .
> COMMENT:
> Yup. In other words, it's still a big mystery, and weird one. The idea
> that its future posiblity, 20 years ago, might have been rationally
> used to uphold the development of a multi-billion dollar industry, is a
> completely out-to-lunch idea. We'd still be waiting for human insulin.
No, we wouldn't. There were people then who were allergic to pork and
beef insulin, just as there are people now who are allergic to GE
insulin. Other than for those few people, there was no need for GE
insulin. It would have been developed (and nobody's suggesting it
shouldn't have been) simply because it's much cheaper to get insulin out
of a tampered-with tummy bug or yeast cell, than out of a slaughtered pig
or cow. The real mystery is why the regulatory authorities were asleep
at the wheel, and allowed it to be introduced withoug being properly
tested.
> And probably criticized by all the people who complain we still produce
> flu vaccine in chicken eggs.
>> Colleen Fuller:
>> Novo Nordisk withdrew all of its animal insulins from the Canadian
>> market, and most from the US market, in 1995. Novo distributed a broad
>> range of beef, beef/pork and pork insulins (Toronto, NPH, Ultralente,
>> Semilente and Lente, among others and in all three formulations)
>> through Connaught. Eli Lilly withdrew all of its beef insulin from the
>> North American market in 1998. On July 6, it announced it was pulling
>> the remaining two types of Iletin II pork insulin.
>>
>>
>> Steve Harris:
>> Beef insulin is no longer available due to mad
>> cow disease.
>>
>> Colleen Fuller:
>> Without discounting concerns about BSE, most physicians incorrectly
>> believe that beef insulin was withdrawn because of BSE (or antibodies).
>> The fact is that beef insulin was withdrawn by manufacturers purely as
>> a marketing strategy.
> COMMENT:
> "Marketing strategy" meaning anticipation of much stricter regulation
> on injectables made from cow innards (the BSE prion is MUCH tougher
> than the insulin molecule--- you tell ME how they're going to make sure
> you get the insulin and not the prion.)
No. "Marketing strategy" here means forcing diabetics to convert to a
drug more profitable for the manufacturers, regardless of how well it
works. Willbill has pointed out on this newsgroup (misc.health.diabetes)
that bovine products are used in the manufacture of Lantus, for example.
> But you've got me. I didn't think anybody could still be that stupid as
> to continue to produce beef insulin in this day and age, but
> apparently, there are some people who still are.
It's not stupid at all, and it's surprisingly simple. Beef insulin is a
natural product of the highest quality, known from many decades of
experience to be effective and safe (not taking into account things like
BSE), and there is, as yet, no artificial product available to match it.
Much the same way, I suppose, that there is no artificial product to
match the qualities of "beef" leather. The quality of life of people who
use beef insulin would diminish markedly, were they forced to convert to
substitute drugs.
> But let me put it on record here and now, WHY and think it's stupid,
> and predict that more trouble is to come from it. And that you
> disagreed with me.
>> Regulators did not require its withdrawal, and it continues to be
>> marketed in the United Kingdom (where 20% of diabetics use
>> animal-sourced insulin), Australia, India and many, many other
>> countries, along with pork insulin. It is safe, effective and
>> affordable.
> COMMENT:
> Ahem. "Safe" you say?
It's safe in the sense that it is known (from around 80 years of use) to
have no long term side effects. It does not cause cancer, for example.
The same is not yet known for recently introduced drugs such as Lantus.
Beef insulin is also robust (it's not sensitive to hot weather), and easy
to use (for example, it can be mixed in a syringe with other insulin).
Put it in a fridge, and it will last the best part of a century.
> On the basis of *what* BSE-centered studies of beef insulin
> manufacture? How much looking at the issue has anybody really done?
> Where is COCHRANE'S concern about safety issues when we really need
> them?
Do we really need them? Beef insulin has been used continuously for
decades, all through the BSE scares of the last ten years. The
manufacturers are careful in the extreme, where their bits of cow come
from. If BSE in insulin were a problem, wouldn't we know about it by
now? There'd already be a few hundred deaths from this cause, wouldn't
there?
Anyhow, what about the same measures applied to Lantus, for example? It
too uses beef products in its manufacture, and is used by far more people
than beef insulin.
> By the way, regulators did not require withdrawal of beef insulin in
> the US, because they didn't need to. Companies withdrew voluntarily.
> But the FDA does indeed have concerns about BSE in beef insulin
> imported from other countries, and is on record about it.
Entirely properly.
>> Steve Harris:
>> Pork insulin is available just about everywhere,
>> including Canada (where about 200 Canadian still us it).
It's supply is being relentlessly restricted. Here in Germany, Novo has
announced it will withdraw Semilente from the German market. This is a
mere two years after building a new manufacturing line for Semilente,
the old one having broken down due to massive overuse, due to the
increase in popularity of Semilente.
>> Colleen Fuller:
>> IMS data suggest there are roughly 700 people using Iletin II NPH and
>> Regular insulin in Canada. Eli Lilly estimates about 400 people. On
>> July 6, Eli Lilly announced it is pulling the remaining pork insulin
>> from the North American market. Wockhardt, based in India, has applied
>> for a license to market its own brand of pork insulin in Canada, but
>> not in the United States. They have been assisted by Eli Lilly, whose
>> own Canadian supplies will be exhausted by April '06.
> COMMENT:
> Well, good for them. If you can find a little niche market, like people
> who think that vacuum radio tubes give better amplifier sound, have at
> it. I'm sure that being Canadian, you'll want the government to pay for
> it, though.
Which raises the much bigger philosophical question, should we diabetics
be expected to have to chose from amongst whatever drugs Novo, Lilly and
Aventis find profitable to make? That is pretty much the way things are
at the moment. The other extreme would be for regulatory bodies to
specify rigidly what products are to be made. Doesn't seem much better.
The real problem is, the supply of insulin is a monopoly, not a free
market. If I had my way, there _would_ be a free market, one in which
the existing monopolistic powers would be severely curtailed.
>> Colleen Fuller:
>> The biggest impediment to those who try to manage their blood sugars
>> effectively is doctors who are ignorant of the issues and evidence
>> regarding animal-sourced insulin.
Largely because the insulin manufacturers have great influence over what
doctors learn.
>> In 1995, Humulin was among the top 10 drugs with reported serious
>> adverse side effects in the United States. Humalog has racked up an
>> astonishing number of reported serious ADRs in Canada. Although these
>> are suspected links only, there has been no attempt in Canada to
>> determine causality. (I recognize that this would be difficult;
>> however it's impossible to say how difficult since the national
>> regulator hasn't ventured to find out.). The point is that the
>> experiences patients have had are very real, and the attitude of many
>> physicians is appalling. These patients are accused of being nothing
>> more than some kind of modern-day Luddites, when in fact what's
>> happened to them is that they were using the wrong species of insulin.
>> There are too many irresponsible doctors to whom these often desperate
>> patients turn - and this hard-hearted and ignorant attitude is what
>> they have to deal with. It's really unbelievable.
Been there, done that, got quite a few teeshirts. I tried Humalog once,
as a correcting drug, not (thankfully) my main insulin. The stuff died
after two days of at least two summer holidays. It died within a few
weeks of my carrying it back and forth with my normal insulin. ~80% of
the total I was ever prescribed ended up being chucked out.
When I needed an insulin change a few years back, my last doctor told me
"convert to Lantus, go onto the pump, or stay with GE NPH[*]. I refuse
to even consider animal insulin.". I found a more suitable doctor.
[*] For those not in the diabetic groups, NPH is a delayed action
insulin, delayed by protamine extracted from fish testicles, and is
notorious for causing symptom-less hypos (low blood sugar), and having an
enormous action peak around 4-6 hours after injection. YUCK!!
>> It's also unbelievable that there are some doctors who compare a vital
>> life-saving medicine like animal insulin to vinyl records and 8-track
>> tapes. They shouldn't be treating patients in the real world of drug
>> safety and effectiveness. Two national regulators - Canada and the
>> United Kingdom - have concluded that there is a subset of diabetes
>> patients who require animal insulin. After many years of persistent
>> work by insulin-dependent diabetics, a Health Canada representative
>> stated before the Parliamentary Standing Committee on Health, that
>> "there very clearly are Canadians who need animal-sourced insulins to
>> manage their diabetes. We have no doubt about that at all...The
>> current science [sic] knowledge does not really enable us to
>> understand why the synthetic insulin or the human insulins do not work
>> as well for some people as do the animal insulins, but clearly that is
>> the case..." (Evidence before the Parliamentary Standing Committee on
>> Health, presented by Julia Hill, Director General of the Biologics and
>> Genetic Therapies Directorate, Feb 2003) In July, the MHRA
>> acknowledged that some people must have guaranteed access to natural
>> (beef and pork) insulin. The Australian government has recognized this
>> situation with its approval of Wockhardt's beef (but not pork)
>> insulin, which is sold there by Aventis. In India a battle is raging
>> to protect animal-sourced insulins and domestic control over the
>> insulin market. In Europe many diabetics are fighting to maintain
>> access to pork insulin.
Indeed so, one of them being me. Where did this notion arise, that only
diabetics who "absolutely require" natural insulin should be prescribed
it, rather than those for whom, like me, it simply works better?
>> Of all the comments and ignorance exhibited by this physician, his
>> dismissal of the actual and sometimes traumatic experiences diabetics
>> have had is very disturbing. Patients who experience serious adverse
>> side effects have to fight for recognition without the support and
>> advocacy of doctors who claim to have the patient's best interest at
>> heart. No wonder so many patients feel demoralised and humiliated.
> COMMENT:
> STOP! ENOUGH! Here's where we get to brass tacks. The Cochrane review
> you've already quoted is (despite its unfortunate politics) still the
> best that exists on the subject, and it contradicts you. You cannot
> have it both ways. Let me quote from COCHRANE, and please note my
> emphasis *** asterisks:
> Richter B, Neises G. 'Human' insulin versus animal insulin in people
> with diabetes mellitus (Cochrane Review). In: The Cochrane Library,
> Issue 3, 2002.
> Main results
> Altogether 2156 participants took part in the 45 randomised controlled
> studies that were discovered through extensive search efforts. Though
> many studies had a randomised, double-blind design, most studies were
> of poor methodological quality. Purified porcine and semi-synthetic
> insulin were most often investigated. ***No significant differences in
> metabolic control or hypoglycaemic episodes between various insulin
> species could be elucidated. Insulin dose and insulin antibodies did
> not show relevant dissimilarities.***
Yep. The studies were, in general, of poor quality and inconclusive.
The results of the many studies quoted were not consistent with
eachother.
There was, and is, however, massive and incontrovertible anecdotal
evidence that GE insulin produces problems for many people. There is no
convincing evidence and no reason whatsoever to believe that GE insulin
is free of problems.
> Authors' conclusions
> **A comparison of the effects of human and animal insulin as well as of
> the adverse reaction profile did not show clinically relevant
> differences.**
Yes. As you mention, most of the testing was poor quality, and didn't
take into account quality of life issues. Tell me, in treating a chronic
disease, is there anything apart from quality of life which is worth
testing for?
> Meanwhile, you want the entire system to change because of a couple of
> hundred diabetics, who say they don't get the same results with the new
> stuff as the old.
It's not a "couple of hundred". It's many, many thousands, probably
millions, worldwide. You're dismissing their problems as something
frivolous. Amongst them are a few who are allergic to GE insulin, who
will die rapidly and nastily without natural insulin. One of them is
called Sabine Hancl and posts here (misc.health.diabetes) from time to
time. Her worst experience was being admitted to hospital in an
emergency and being injected with GE insulin, despite her wearing a
medical tag stating her allergy to it. Within hours she was on the brink
of death, with kidney failure amongs other things. She spent a year in a
psychiatric clinic as a result.
> But there we have the difficulty. I wish I had nickel for every person
> I've heard say "Every person should be guaranateed the same standard of
> health care by his or her society"! And I wish I had a nickel for
> every patient who told me "But doc, I'm not LIKE everybody else! Drugs
> react completely OPPOSITE on me!!" And I wish I could put the two
> groups together to argue out the consequences of these two points of
> view, one political and one personal---- because in reality they make a
> mighty poor mix.
In this particular case, natural insulin works better for many people,
amongst them me. There has never been any convincing evidence that GE
insulin works consistently well. For many people, the difference between
natural insulin and artificial is the difference between being a fully
functional healty person and an invalid, barely able to hold down a job.
The production of natural insulin is fully economic and profitable. I do
not find it unreasonable to require it to be manufactured.
> SBH
--
Alan Mackenzie (Munich, Germany)
Email: aacm@xxxxxxxx; to decode, wherever there is a repeated letter
(like "aa"), remove half of them (leaving, say, "a").
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