When I asked: 'Did the lab animals used in testing rezulin before it went to clinical trials show that there was the danger of severe liver disease in people who didn't already have severe liver disease?

Medicalbreak said: 'Yes. See the evidence provided. As stated at length earlier, this class of drug is inherently toxic due to its mechanism.'

I say: The 2001 study you referred to was done after rezulin was approved for use in humans in 1997.

This study, done after troglitazone was approved for human use said: 'A similar mechanism of inhibition has recently been described for glibenclamide (Stieger et al., 2000), known to induce cholestasis in a few cases in man (Krivoy et al., 1996). For this compound, only a weak response was observed in the rat cholestasis model, in agreement with the weak in vitro Bsep inhibition.' (CHOLESTASIS IS THE OBSTRUCTION OR BLOCKAGE OF THE TRANSPORT OF BILE SALTS. BSEP IS RESPONIBLE FOR THE TRANSPORT OF BILE)

Does that mean that glibenclamide induced cholestasis in some humans but only had a weak effect in rats? The humans who experienced cholestasis didn't get a weak effect. The rats didn't predict that.

The study also said: 'In patients with hepatic impairment, troglitazone sulfate was found to accumulate about 4-fold in plasma, with a 3-fold-increased half-life (Ott et al., 1998. '

This was found in humans after the drug was approved - well after the lab animal safety tests.

It also said: 'In rats, which were treated with 25 mg/kg troglitazone to produce a maximal cholestatic response, the troglitazone plasma concentration was in the range of ~13 nmol/ml.'

And: 'Typical daily troglitazone doses in man are in the range of 400 to 600 mg, producing troglitazone plasma concentrations of 1 to 2 µg/ml (2 to 4 nmol/ml).'

So, they gave the rats a dose which is the equivalent of about 1,750mg for an 11 stone human. And after the dangers to humans had been seen in humans.

The study also said: 'A quantitative extrapolation of the cholestatic effect observed in rats to man is not possible, because of species-specific differences in the process of bile formation and in the disposition of troglitazone.'

Species-specific differences!? Is there such a thing?
-----------------------
Medicalbreak said: 'And in what way was any of your references evidence of misleading animal research?' After I had linked to some studies where lab animals were used for testing psychotropic drugs.

I say: They were just to show that lab animals were used.
----------------------
I think you should stop trying to defend the use of vivisection. It really is not science.

quote:

The humans who experienced cholestasis didn't get a weak effect.

Thats just your opinion - what was the actual degree of effect ?

quote:

I say: They were just to show that lab animals were used.

ok, so do you have examples of misleading animal research?

quote:

I say: The 2001 study you referred to was done after rezulin was approved for use in humans in 1997.

Martin, I think we went through this before, didn't we, where the scientific animal testing community seemed to find out about health problems, AFTER they were discovered in humans, and this is put forward as animal testing being a reliable indicator, when actually animal testing didn't show these results before the drugs were rolled out for human use. And no doubt the animals that would show similar effects were used in the data in the later research, discarding the animal tests that didn't show this (like Thalidomide).

Well spotted...

quote:

Originally posted by Thewitchisback:

quote:

I say: The 2001 study you referred to was done after rezulin was approved for use in humans in 1997.

Martin, I think we went through this before, didn't we, where the scientific (sic) animal testing community seemed to find out about health problems, AFTER they were discovered in humans...

...as is ALWAYS the way!

quote:

Originally posted by TheAM:

quote:

Originally posted by Thewitchisback:

quote:

I say: The 2001 study you referred to was done after rezulin was approved for use in humans in 1997.

Martin, I think we went through this before, didn't we, where the scientific (sic) animal testing community seemed to find out about health problems, AFTER they were discovered in humans...

...as is ALWAYS the way!

..."the scientific (sic) animal testing community" as opposed to the more enlightened scientists who are now seriously questioning "animal testing", of course.

A good place to find some quotes from these enlightened scientists:

Enlightened Scientists Quotes

Witch said: 'Martin, I think we went through this before, didn't we, where the scientific animal testing community seemed to find out about health problems, AFTER they were discovered in humans, and this is put forward as animal testing being a reliable indicator, when actually animal testing didn't show these results before the drugs were rolled out for human use. And no doubt the animals that would show similar effects were used in the data in the later research, discarding the animal tests that didn't show this (like Thalidomide).'

I say: And in the same way I correctly chose every winning team in today's football fixtures - after I had heard the results on telly. It's a great system. It never fails to find winners.

Vivisection really isn't science.

quote:

Originally posted by MartinGBUK:
Witch said: 'Martin, I think we went through this before, didn't we, where the scientific animal testing community seemed to find out about health problems, AFTER they were discovered in humans, and this is put forward as animal testing being a reliable indicator, when actually animal testing didn't show these results before the drugs were rolled out for human use. And no doubt the animals that would show similar effects were used in the data in the later research, discarding the animal tests that didn't show this (like Thalidomide).'

I say: And in the same way I correctly chose every winning team in today's football fixtures - after I had heard the results on telly. It's a great system. It never fails to find winners.

Vivisection really isn't science.

I say: And in the same way I correctly chose every winning team in today's football fixtures - after I had heard the results on telly. It's a great system. It never fails to find winners.

So Martin, was the animal research before the drug was released different ? Can you highlight those studies?

I have replied already, but Im guessing the admins have removed yet another post, be nice to know for what reason. Maybe Malkie, I mean Medical asked them to do so.....

Basically I said no, most people (other than those who work for the industry) wont be able to show you such data, as most failed testing wouldnt be made public, as many others have said before. Even if testing is then shown to be flawed on release, the wannabe scientists will retest using more species to find some level of correlation, which there are also many examples of. I also suggested that this is probably why you like making this point so much, as you work within the industry and know this to be the case.

OK admins/Malkie/MB?? Its OK Ill copy it this time. Sigh.... Why start such debates on your forum if you only want one side, why not just make one sided programs as you usually do. Forums not such a good plan for true discussion.

There are only 10 types of people in the world — those who understand binary, and those who don't.

Interesting pair of reviews here. Animal testing really is a bad predictor.

(1) that reviewed drugs whose toxicity to humans caused their withdrawal from the market
(1960-1990), only 4 out of 24 cases were predictable from animal data. In another
review (2) only 6 of 114 human toxicities had animal correlates.

Heywood R, 1990; Clinical toxicity - could it have been predicted? in Animal Toxicity Studies: their relevance for man, (Lumley and Walker, Eds) p57-67
Spriet-Pourra, C and Auriche, M, (Eds) 1994, SCRIP Reports, PJB, New York

quote:

Originally posted by RandomElement:
I have replied already, but Im guessing the admins have removed yet another post, be nice to know for what reason. Maybe Malkie, I mean Medical asked them to do so.....

Basically I said no, most people (other than those who work for the industry) wont be able to show you such data, as most failed testing wouldnt be made public

Indeed, the secretive nature of the industry is a very real problem. As one of the papers presented by the DoH and discussed on here in 2006 is testament to.

`There are few published analyses of comparative animal-human toxicity data on
pharmaceuticals, with progress presumably inhibited by the perceived confidential
nature of such data.' (page 57)


6. Olsen H et al (2000), `Concordance of the Toxicity of Pharmaceuticals in Humans
and in Animals', Regulatory Toxicology and Pharmacology 32, 56-67

Medicalbreak said: 'So Martin, was the animal research before the drug was released different ? Can you highlight those studies?'

I say: You don't believe that studies in rats said that humans without severe liver disease would be in danger of severe liver disease?

Now here is another amazing piece of information published in last months issue of Journal of the Royal Society of Medicine:

--------------

quote:

http://www.curedisease.net/latestnews.shtml


Studies in dogs and monkeys no more informative than tossing a coin

The common claim that 'virtually every medical achievement of the last century has benefitted to some extent from animal research' is an outrageous abuse of the trust placed by the public in our most prestigious academic institutions, according to science journalist Robert Matthews: see BBC Focus Magazine article (February 2008)

Robert Matthews has re-analysed the data from a much quoted published paper assessing the predictivity of dogs and monkeys for the toxicity of anti-cancer drugs and found that the predictive values quoted were calculated incorrectly. When calculated correctly, "the data provide no statistically credible evidence that these animal models contribute any predictive value, either separately or in combination." This stunning piece of work is published in the February issue of the Journal of the Royal Society of Medicine, for which a subscription is required to view the article.

Robert Matthews has also published an article (subscription required) in the 16 February issue of New Scientist, in which he observes: "Few [studies] provide enough data to allow the value of animal studies to be worked out; those that do suggest they are no more informative than tossing a coin."

Sorry for taking so long to get back in contact, it took an age to get a copy of one of the studies you recommended because it was not available on line.

Sadly, the overall conclusion is that the statements you post are not supported by the text in the publications you reference. I'm slightly concerned that you haven't actually read the articles, but are merely reposting the (inaccurate) interpretation from someone else who may (or may not) have read the actual data involved.

For example, in your most recent post you reference (J R Soc Med 2008;101:95-98), with the claim "Studies in dogs and monkeys no more informative than tossing a coin". However, this is not the claim that the actual article makes - more that methods used to calculate if animal research is predictive or not are (in the authors opinion) not suitable. The actual conclusion of the article (in the authors opinion) is that we don't have enough properly controlled data to mathematically prove one way or another.

The authors main issue is that most available data is generated from a variety of sources under slightly different conditions making pooling and direct comparisons mathematically unstable. The author does not claim that animal research doesn't work or isn't predictive, he is actually an advocate of greater systemic undertakings to quantitively support the use of animals.

Another study you reference (Heywood R, 1990; Clinical toxicity - could it have been predicted? in Animal Toxicity Studies: their relevance for man, (Lumley and Walker, Eds) p57-67 ) was the one I had trouble obtaining. It is potentially the most misleading article you reference, because the conclusions you've attached to it are not actually the conclusions of the data in the article. The biggest issue with this study is that it is based on extremely limited clinical data. Furthermore, they included toxicities for which there was no animal data (ie experiments not performed) under the heading of "no animal correlate" which is completely misleading. A further study (Toxicology Letters
Volumes 102-103, 28 December 1998, Pages 535-538) found "Analysis of the time to first appearance of human toxicity in the preclinical species revealed that 95% of preclinical findings correlated with human toxicities were first detected at 1 month or less"

I'd urge you to read the source data before passing someone elses interpretation of it on as fact, because in both of the references you've provided, the data does not support the conclusions they make.

Similar I've heard before that "45% of healthcare professionals believe animal research works", whereas the actual fact is that of all of the healthcare professionals surveyed, only half (50%) returned the questionaire. Of that half, 90% said animal research worked - hence, its often reported that only 45% of healthcare professionals think animal research works. Not exactly an honest report - is it?

"For example, in your most recent post you reference (J R Soc Med 2008;101:95-98), with the claim "Studies in dogs and monkeys no more informative than tossing a coin". However, this is not the claim that the actual article makes - more that methods used to calculate if animal research is predictive or not are (in the authors opinion) not suitable. The actual conclusion of the article (in the authors opinion) is that we don't have enough properly controlled data to mathematically prove one way or another."


The author quite clearly states, "the data provide no statistically credible evidence that these animal models contribute any predictive value, either separately or in combination.". When are you going to accept what an article or author ACTUALLY says instead of putting your own dishonest, personal spin on them?


"The authors main issue is that most available data is generated from a variety of sources under slightly different conditions making pooling and direct comparisons mathematically unstable. The author does not claim that animal research doesn't work or isn't predictive, he is actually an advocate of greater systemic undertakings to quantitively support the use of animals."

I beg to differ, the author quite transparently states that while their arent many available studies that allow the worth of animal experiments to be evaluated, that "those that do suggest they are no more informative than tossing a coin." It is clearly no wonder, given this fact, that the proponents of the vivisection industry, including their pals in media and government, are fighting so hard to stop the first ever scientific-evaluation of animal-experiments.