Drugs

[mobeyone]

Do you think they were http://www.sky.com/skynews/article/0,,30100-13514213,00.html testing something else?

 

[hardo]

such as...?

 

[grober]

In lots of pharmaceutical companies and many times in the history of medicine the researchers who engineer the drug test it on themselves first, -as an act of faith and to show confidence that they got things right. Wonder why they didnt do that this time??????????????????????????? The American company Parexel http://www.parexel.com/ running the drug trial was only a subcontractor to the German Company TeGenero who manufacture it. http://www.tegenero.com/news/statement_re_tgn1412/index.php Its a bit misleading to call it a drug since its appears to be a sort of artificial monoclonal antibody which is a bit different from the normal molecules we associate with conventional drug manufacture. It appears to have triggered some sort of massive allergic response in the bodies of the volunteers. The human casualties have now been "dumped" into the National Health system who are trying to help the victims as best they can. God help them all. The lawyers will have a field day!

 

[glojo]

Hi Grober,
The side effects appear staggering and as a lay person I suspect a massive overdosing????? These were fit young men, who were highly paid to take these drugs.(minimum of £2000) Listening to the placebo taking candidate the drugs were actually injected so I suppose that might explain the rapid reaction. We were also told they were anti-inflammatory drugs??? Is that the same as what you have mentioned?

Drugs clearly have to be tested before having a licence, however as I stated on another thread, if someone offers large sums of money to test a drug then I would walk away. As you have mentioned why not have manufacturers test these things at very low doses, and gradually increase it until any side effects are noticed?

Over the years I have had numerous anti-inflammatory drugs that have been eventually withdrawn because of terrible side effects. (These drugs have been licenced but as we know they still have side effects) The anti inflammatory drugs I am now taking are causing rashes that make my skin bleed!!! (I've stopped taking them )

When I was in the military we were regularly asked for volunteers to attend a certain **NBCD testing laboratory to help find a cure for the 'common cold' It was always the clever academic types that volunteered. They believed it would be perfectly safe and they were helping soceity.

** Nuclear Biological Chemical Defence No doubt there is a more modern fashionable term.

John

 

[grober]

It would appear that this drug was going to regulate certain aspects of the bodies immune system specifically the T cell. This was an attempt to combat the auto-immune diseases such as Multiple Sclerosis or Rheumatoid Arthritis where the body attacks itself. There is an explanation here http://www.tegenero.com/research__development/scientific_background/index.php
Instead it seems to have triggered some disastrous over reaction in the immune system in this case. The medics appear to be baffled so far.
Its a tragedy for all involved and may well set back drug research in this area for years. One has to feel for the families and young victims in this terrible situation.

 

[glojo]

It would appear that this drug was going to regulate certain aspects of the bodies immune system specifically the T cell. This was an attempt to combat the auto-immune diseases such as Multiple Sclerosis or Rheumatoid Arthritis where the body attacks itself. There is an explanation here

Thank you very much indeed for posting the most informative link. It sounds like this laboratory is involved in life saving research?

Is this one sentence relevant to what might have happened?

To avoid an overshooting immune reaction that bears the danger of harmful uncontrolled proliferation of lymphocytes and massive secretion of inflammatory cytokines, activation of T cells and other cells participating in an immune response must be effectively turned down.

In these particular circumstances no sane person would wish injury on anyone, I totally accept the reactions to this drug might be beyond anything that might have been predicted. These students went into this with there eyes wide open? Is it probable that they signed disclaimers???

I do however hope they all fully recover and we all learn lessons from this incident. Like you I fear that this might be a terrible set back for drug research.

Our servicemen in the early 1950's - 60's witnessed nuclear explosions and were deliberately exposed to harmful radiation coontamination, they neither volunteeered, nor were they paid any extra money. Quite a few have since died from the side effects of these tests so I suppose that might effect my feelings towards these well paid young men that volunteeered to be injected with experimental drugs?

John

 

[grober]

John,
the phrase " an overshooting immune reaction that bears the danger of harmful uncontrolled proliferation of lymphocytes and massive secretion of inflammatory cytokines" does seem to fit the bill doesn't it. Still we will have to wait for the results of the enquiry. I was disturbed to read "The Times said senior doctors were concerned that all six victims had been given the experimental drug at the same time. The newspaper reported guidance in The Textbook of Pharmaceutical Medicine, which says such practices can be "very difficult to manage" and "put subjects at unnecessary risk". No doubt more information will be forthcoming in the next few days. I guess the two guys who were giving the placebo in the trial are feeling pretty lucky right now.

 

[glojo]

Still we will have to wait for the results of the enquiry.

I guess the two guys who were giving the placebo in the trial are feeling pretty lucky right now.

I totally agree with every word, especially the above two sentences.

The victims will be demanding both sympathy and compensations; the media will be looking to make this appear as sensational as possible and sadly the truth will be buried.

John

 

[Dieter]

Hi,

I have undertaken many of these phase 1 studies, which are NOT designed to elicit effects but are primarily designed to examine bioavailability (blood concentrations, time in blood etc.) and in the studies in which I have partaken, as Grober rightly points out, a responsible clinician has often taken a (small) dose first. These initial studies are usually carried out with sub-clinical (inneffective) doses and are often followed up by subsequent studies using higher doses where onset of side effect liabilities may be seen.

In all of the studies in which I partook administration of compounds was never significantly staggered. Unfortunately, as is always the case, hind sight is a wonderful thing.

The problem here may have been that the 'drug' under test was a humanised antibody (CD28 Mab) which didn't appear to show (m)any side effects in other mammals. However the problem with this trial is that the way the drug acts may be the direct cause of the side effect and, unfortunately, this 'effect' may, therefore, only be seen in humans (as intended target of humanised antibody). This raises the question of how to carry out safety testing on agents designed solely to work in humans.

I believe the Company genuinely thought their agent was safe but unfortunately their hypothesis (that activation of T-cells inappropriately would be beneficial) was unsound. Unless compounds are 'me to's (i.e. like other drugs on market) there is always an element of hypothesis testing when drug development moves into man.

Also to enrol on a clinical trial one has to give informed consent. This informed consent can only be based on current knowledge etc. so there is always a risk (usually low). So unless the agencies involved can be proved negligent (wrong dosage, contamination etc.) this will have to be looked upon as an (extremely) unfortunate accident.

Hopefully all 6 affected trialists will regain full health in the near future.

Cheers,

 

[Satch]

Got to say that "overshooting immune reaction that bears the danger of harmful uncontrolled proliferation of lymphocytes and massive secretion of inflammatory cytokines" sounds pretty much the key.

Cytokines are chemical messengers forming an integral part element of the immune system. As messengers, cytokines tell other immune cells to activate, grow or even die. Dr. Lionel Ivashkiv, a rheumatologist, explains that “cytokines regulate the immune system responses and can drive the inflammatory process.”

That could explain why these unfortunates are in such a terrible state.

 

[grober]

Collateral damage

Dieter,
always interesting and informative to hear from a forum member with direct experience of a particular situation. I wonder how "informed" the consent was. Did the participants know the putative theraputic agent was designed solely to work in humans AND that as such prior animal testing was no real indicator of its safety in man. Its a pretty complex field of research. Many of these volunteers seem to do this work on a fairly regular basis and maybe were lulled into a false sense of security about the risks involved. I dont know. I'm just asking? If these unfortunates end up with permanent disabilities it will be interesting to see what attitude the companies adopt. Have they any sort of endemnity insurance? No doubt the companies position legally will be bullet proof, but whether they feel any MORAL obligation to compensate this group of people whose health may be permanently damaged remains to be seen. There are parallels to be drawn with the nuclear tests of the 50 and 60s John mentioned. Although the circumstances are very different the moral dilema of how you treat the casualties remains.

 

[glojo]

I feel guilty about my attitude on this terrible incident, but surely the people that are paid a minimum of £2000 to test new products must accept they are NOT going to be given black-jacks or strawberry chews???? They hire out their bodies and would no doubt sign a disclaimer. I believe two of these individuals are still on life support machinery, I hope against hope that they improve and there will be no long term effects. I readily apologise for my post and hope there are no relatives of these folks reading this thread

I have made sure my son reads the newspapers and watches the news, just in case he was ever tempted to take the money and let uncertified drugs be injected into him.

Does the intravenous injection itself carries a very small risk? These folks are having drugs injected into their healthy bodies, I thank them for that because obviously I am at the other end of the chain.

I have given copious amounts of blood in my time (one pint at a time ) and the most I received was a cup of coffee and THREE biscuits (I was a bit peckish) I went into this with my eyes wide open and accepted hate bruising

John

 

[Dieter]

Hi,

For other comments re possible problems in testing 'humanised' materials click here:

http://news.bbc.co.uk/1/hi/health/4817178.stm

Cheers,

Dieter

 

[Howard]

On the news today, at least two of the participants are expected to be in a coma for at least 12 months ( how do they tell these things, i thought comas were unpredicable).... Thats bad news indeed ....

However, the newsreaders today are having a field day using quotes like ' Another medical procedure gone horrifically wrong ' with the gravitas and emphasis on the word 'horrific' .....

Apparently they were given doses 500 times less than the doses given to the test animals, monkeys and rabbits... one guys head swelled up to 3 times its normal size (now that would be something to see)

They are playing it up like it is another NHS blunder when in reality it was private testing ....

This country loves to sensationalise doesn't it ...

 

[grober]

A close shave?

Another close shave??
http://www.sky.com/skynews/article/0,,30100-13514092,00.html
and waiting in the wings? http://www.boehringer-ingelheim.com/biopharm/news/news4_20031117.htm and http://www.wuerzburg.de/biomed/english/news/index.html?fCMS=f97c40e0c486cf24f46b862df4726869

 

[Howard]

Here we go , they are all coming out of the woodwork now ....

There was a report earlier about one of the coma guys, who , and i quote ....

'Was showing no signs of life at all, until his brother held his hand and a tear rolled down his cheek .....'

Pass the sick bucket please ..... its reading like a poor novel ....

 

[glojo]

I think we must accept these are well liked, loved respected young men with families. I have been vocal in my criticism of their decision to partake in these tests, but they are now sadly suffering the consequences of that decision. It is sickening to see folks taking advantage of this tragedy, sickening but expected. The survivor being interviewed in a very nice hotel room, with a copy of the Sun in front of him just makes me feel nothing but contempt for him. He is yet again making money out of this company??

I am surprised that this is a German based company yet doing tests in the UK? Are the actual research laboratories over here?

I can fully understand the victims being admitted into a National Health Hospital as NHS hospitals usually have far superior nurses, equipment etc. I just hope the company pays ALL the costs of the nursing, plus extra nursing, hire of equipment etc. to allow that hospital to look after newly admitted patients requiring Intensive Care treatment.

I also believe that most information now being released about the condition of these victims is made up by folks that want to influence the story one way or the other.

Never let the truth get in the way of a good story.

John

 

[glojo]

I am surprised that this is a German based company yet doing tests in the UK? Are the actual research laboratories over here?

I never take for granted what newspapers report, but it is now being alleged that this company were refused a licence in Germany to carry out tests on humans????

I asked the question without the benefit of hindsight, it just seemed suspicious.

My point here is for those that think it perfectly safe to take money and test drugs. Before doing it..... Think long and hard. Never risk abusing your body.

German company testing their product in a different country??????????? Ring, ring, ding dong. I am sure foreign companies have done this many many times, but why, if the company is clever enough to develop the drugs in their homeland, then why come here just to carry out tests on human beings??

John

 

[Dieter]

Hi,

The practice of Companies testing drugs in other Countries is widespread. It's (usually) nothing sinister and more reflects (perhaps) the reputation of the Clinical Unit (in this case Paraxel).

I'm sure Germany has no more nor no less rigorous rules concerning testing of new compounds in humans. As long as TeGenero are citing accurately their preliminary animal data (i.e. no side effects in more than one mammal species) then this response was as much a shock to them (will Company survive?) as to their trialists.

Consenting to take agents which have shown no significant side effects (at doses to be administered) in mammals is the main consideration (especially using human targeted (antibodies etc.) agents) for volunteers i.e. as agent has not been tested in man there must be an unknown (usually small) risk.

These sorts of trials are being carried out everyday all over the world and this specific catastrophe (though there are now signs that all 6 trialists are showing variable rates of recovery) is almost unique.

It's already apparent that future studies (especially with 'humanised' agents) will require a different approach and the use of skin tests etc. has already been mooted.

Ultimately Drug Companies need to obtain human data and all volunteers must realise (as I did) that there is always a finite risk. Even with 'safe' drugs on the market individuals respond differently.

The 'volunteer' system has worked very well and (with added safeguards for specific types of agents) should continue to work well in the future.

Cheers,

 

[glojo]

Hi,

The practice of Companies testing drugs in other Countries is widespread. It's (usually) nothing sinister and more reflects (perhaps) the reputation of the Clinical Unit (in this case Paraxel).

The allegation (I would prefer rumour) is that the German authorities refused to allow the tests.

I accept totally the practice is widespread, that is not hte issue.

John