NationStates Jolt Archive

Now what do you think this story is about... I thought it'd be about trying to save the lives of some witnesses in a drug related crime trial or something, but no. It's about 6 young men who were the guinea pigs for the clinical trial for a drug.

One of the two participants given a placebo instead of the drug, yesterday gave a graphic account of the distress caused. "The test ward turned into a living hell minutes after we were injected," said Raste Khan, 23, a television technician who had signed up for the £2,330 fee for the trial. "The men went down like dominoes. They began tearing their shirts off complaining of fever, then some screamed that their heads were going to explode. After that they started fainting, vomiting and writhing around in their beds."Scary.

http://society.guardian.co.uk/health/news/0,,1732973,00.html

edit: this is why animal testing can be completely useless

So let me get this straight. Because of one incidence where animal testing *MAY* have proven less than sufficent as practiced, all incidents where it has proven effective including the development of routine life saving surgical proceedures, is rendered retroactively ineffective?

Seriously. WTF.

There's an inherent risk in any form of testing - the participants must have signed agreements stating something to this effect. Bad luck and/or roll of the dice I guess.

Bet you its contaminated doses, or some overworked nurse who gave them an overdose.

edit: this is why animal testing can be completely useless
You must be joking. This is why animal testing must be used more before any drugs are given to people.

There's an inherent risk in any form of testing - the participants must have signed agreements stating something to this effect. Bad luck and/or roll of the dice I guess.

Bet you its contaminated doses, or some overworked nurse who gave them an overdose.It's bad practice to administer more the drug to more than one patient at a time, especially when it hasn't yet been tested on humans before. As opposed to just 1 guy being seriously ill it is now 6.

It's bad practice to administer more the drug to more than one patient at a time, especially when it hasn't yet been tested on humans before. As opposed to just 1 guy being seriously ill it is now 6.
In many ways it's lucky the side effects came up so rapidly - a second test group was scheduled to be given an even higher dose later than afternoon.

I heard that their heads swell up to three times their size. WTF? How is that even possible?

Reminds me a lot of Total Recall.

You must be joking. This is why animal testing must be used more before any drugs are given to people.The drug had been tested on animals. This side effect didn't show up.

Animal testing can only alert us to possible side effects of drugs. In some cases drugs may have side effects in other animals that would not occur in humans. Due to the complexity of biochemistry in all life forms any effect of a drug in one animal is not then a given in another. In fact it is possible that reliance on animal testing may have prevented discoveries of drugs that would have been on benefit to humans simply because they caused harm to animals.

edit: Of twenty compounds thought not to cause cancer in humans, nineteen did cause cancer in the laboratory animal.

I heard that their heads swell up to three times their size. WTF? How is that even possible?

Reminds me a lot of Total Recall.
LOL, Fluid.

I don't have a problem with Human testing, i do have a problem with 'animal' testing.

So let me get this straight. Because of one incidence where animal testing *MAY* have proven less than sufficent as practiced, all incidents where it has proven effective including the development of routine life saving surgical proceedures, is rendered retroactively ineffective?

Seriously. WTF.

Read the last bit again:

"edit: this is why animal testing can be completely useless"

rather then how you seem to be reading it:

"edit: this is why animal testing is completely useless"

Well fuck. That's pretty damn crazy. Two of the men are still in critical condition.. Even after a few blood transfusions (I'm not sure of the exact amount they've had) to try and flush all the drug out. Argh, I heard how they were passing in and out of consciousness and screaming. Would be horrible to be around that.

Nice drug, not sure what it's supposed to fix ...

It was to treat multiple sclerosis, rheumatoid arthritis and leukaemia.

They think the drug may have caused extreme anaphylactic shock, which is more a problem with their immune system than the drug. Which is some what ironic considering that the drug was supposed to activate the immune... just not that much though.

The drug was an anti-inflammatory intended for use to treat leukemia.

From what one of the participants said (one of the two who were given placebos), they were given somethign like 12 pages of documents to read, and a couple of minutes to read it befoer signing. Basically, they were rushed through all the disclaimers and what-not. Not that the disclaimers said, "Please not, this drug will give you multiple organ failure and cause your head to expand by a factor of 3", I'm sure, but nevertheless, they weren't given time to read the docs, which did mention anaphalactic shock.

As far as animal testing goes - it is still useful. It's regrettable, perhaps, but it does allow a lot of dangerous stuff to be spotted before it reaches this stage. There are other examples of animal testing giving bad results (for example, Guineau Pigs are killed by penicillin... D'oh!), but on the whole, it works.

It was to treat multiple sclerosis, rheumatoid arthritis and leukaemia.

They think the drug may have caused extreme anaphylactic shock, which is more a problem with their immune system than the drug. Which is some what ironic considering that the drug was supposed to activate the immune... just not that much though.

Maybe the doses were way too high.

Maybe the doses were way too high.They were supposed to have been given 1/500th of the LD-50 for animals. It seems almost impossible that they were given an overdose.

They were supposed to have been given 1/500th of the LD-50 for animals. It seems almost impossible that they were given an overdose.

Must be really powerful stuff! Or incompatible with the human body.

So, I guess it will take a little longer to get approved for general use?

The drug had been tested on animals. This side effect didn't show up.

Animal testing can only alert us to possible side effects of drugs. In some cases drugs may have side effects in other animals that would not occur in humans. Due to the complexity of biochemistry in all life forms any effect of a drug in one animal is not then a given in another. In fact it is possible that reliance on animal testing may have prevented discoveries of drugs that would have been on benefit to humans simply because they caused harm to animals.

edit: Of twenty compounds thought not to cause cancer in humans, nineteen did cause cancer in the laboratory animal.

They really should use pigs more often for these types of studies, even though pigs are a pain in the butt to use. Their biochemistry is one of the closest to humans that we know of.

Anyone think we should consider using prisoners (especially lifers) for drug trials like this?

If anything it would go some way towards meeting the costs of their incarceration.

Law firms and the press would have a fucking hayday if we tried to use prisoners for drug testing, but really, it is the only realistic solution. Prisons are overcrowded, often with petty offenses, but there are those repeat, violent offenders who are in for life or who are on deathrow. The best way to test the effects of drugs on humans is to test them on humans, why not use said criminals.

Anyone think we should consider using prisoners (especially lifers) for drug trials like this?

If anything it would go some way towards meeting the costs of their incarceration.


no, just you I guess.... damn good thing too you inhumane bastard

[Darn timeout... I regularly preview the following as I'm writing it and only after writing the very last two paragraphs and trying to submit it do I get asked to log in once more... Typical. (Anyway, it is rather long, so maybe you'd rather skip to the end anyway...)]

First of all, a discolsure: I've actually worked for the company that was conducting the trials (not the company that developed the problematic drug itself, but the one they then contracted to do the who trial thing). While I enjoyed working there (admitedly nowhere near the 'sharp end' of the study management process) I feel that I am free of most of the possible inherant bias. But I have obtained a pretty good knowledge of how the whole CRO (Contract Research Organisation) industry works.

An amazing number of drugs trials happen all the time. The company concerned is (or at least was, last I checked) 3rd of 4th in the league table of CROs (depending on how you evaluate them, given that their businessmodels 'spread' across different portions of the R&D->Phases I-IV->Approval->Marketting spectrum) and while it is involved in an enourmous amount of studies, so are its immediate competitors.

The rules for such trials are very heavily set down. A lot of people (myself included) tend to quote Thalydomide as being the 'watershed' point at which heavy regulation got set down upon what had (arguably) been a bit of a snake-oil industry, though this unfairly quarters the whole process in the US, and various other events before and after and all round the world (as well as US) have formed the regulatory practices involved which are being followed. Many of the data-handling practices, for example, are akin to financial-strength regulations or beyond.

But I waffle. The industry records all kinds of 'adverse events', a quite unassuming term that covers everything from the possibility of a mild headache following treatment (from either the 'first in human' healthy volounteers or the terminally ill patient who is receiving full treatment as part of the approval process) to death. But the curve (especially filtering out for unrelated issues such as 'death in service' when the treatment is merely pain-relief of a terminal condition and the standard post-mortem investigations show no connection) is skewed firmly towards the milder end of that range. Indeed, among some recorded 'AE's was Viagra's now much vaunted effect on the male libido... (And, ironically, some of the AEs from 'Viagra as an impotence cure' were the very blood-pressure/heart effects that 'Vigra for its originally conceived purpose' was developed to assist with, for those that needed that particular adjustment. 'Safunnyoldworld!)

On every probability curve, there are going to be extreme cases, and it appears that this is one. Having no direct connection to the study involved (and not wanting to be so insensative as to call ex-colleagues working at NPH who might be closer to the action) I wouldn't want to judge, but I know that standard practice at that stage of the trial should prevent all but the most unexpected issues and (reading between the lines) it looks to me like the most likely problem encoutnered in this instance (barring just being 'extreme end of the bell-curve' unforseen circumstance) is contamination of the compound during the manfucaturing process. Whatever it is, I'm sure this will mean even tighter regulations, but probably more at the R&D/Phase I/Low-Volume Manufacturing levels than Phase III-onwards ones.

Whatever the case, it is not incoceivable that the nattily-titled 'TGN1412' may well succesfully pass (later) clinical trials and go on to cure MS/Arthritis/leukemia/whatever else it was supposed to deal with, a bit like selective use of thalydomide against such as lepropsy (especially after manufacturing has removed the worst chiral forms/isomer and patients are screened to avoid dosing pregnant women), but not without completely stopping the current study, allowing the shock-waves to permeate and toughen up the whole industry against further surprises and the whole process restarted on lessons learnt.

Or it could be dropped altogether. There's a limited patent-protection time for any new drgus, which is already mostly taken up by all the testing procedures involved, and the developer generally likes to claw back some of its original investments (given how many active molecues are aggressively and expensively pursued before being dropped due to toxicology concerns even prior to in-human testing). I thus hope that sufferers of the target conditon(s) don't end up deprived (assuming some other compound isn't brought to market of course).


My complete apologies if the above is too verbose. I find that I'm trying to conduct the same manner of conversation as I would try to have among ex-colleagues, but then expanding it out to explain (probably imprecisely, from an expert's POV) the nuances concerned.


My own opinion? Terrible that it happened, something might have gone wrong (or a previously unknown biological effect has been stuumbled upon) in which case the Parhamaceutical industry and associated businesses (e.g. manufacturers and CROs) and regulatory bodies (FDA, MHRA, all that jazz) will have to learn from that and adjust. My sympathies are with the volounteers and their families and any of the doctors, nurses and other staff (some of whom I may know, though I haven't checked) who might feel traumatised by their involvement.

And, for the record, I still wouldn't be averse to taking part in a Phase III trial, general commitments allowing. Aologies if you find that to be so much bluster, but it's true.

no, just you I guess.... damn good thing too you inhumane bastard

If you read carefully, you'll note that I didn't actually indicate whether it was something I agreed with or not.

I merely asked what everyone thought of the proposal and then suggested one benefit I could envisage.

Anyone think we should consider using prisoners (especially lifers) for drug trials like this?

If anything it would go some way towards meeting the costs of their incarceration.If I were going to consider using prisoners as guinea pigs, then I'd probably do it the opposite way to you suggested. Offer volunteering in clinical drugs testing as a form community service or to reduce fines/sentences. But not extend this program to those involved in more violent crimes such as murder and rape.

[Darn timeout... I regularly preview the following as I'm writing it and only after writing the very last two paragraphs and trying to submit it do I get asked to log in once more... Typical. (Anyway, it is rather long, so maybe you'd rather skip to the end anyway...)]
<snip>From what I've heard about the tests it seems more likely that they've stumbled across an unintended consequence of drug. It seems to be quite novel research. Whilst there has been plenty of research into immuno-suppresant drugs there has been very little in the form of drugs that boost the immune system. That fact that anaphylactic shock is an over reaction of the immune system would seem to give my idea some credence. But then again, it could simply be that they were given an overdose by the administers or that there was fault in the manufacturing process which led to there being higher than expected quantities of the drug.

From what I've heard about the tests it seems more likely that they've stumbled across an unintended consequence of drug. It seems to be quite novel research. Whilst there has been plenty of research into immuno-suppresant drugs there has been very little in the form of drugs that boost the immune system. That fact that anaphylactic shock is an over reaction of the immune system would seem to give my idea some credence. But then again, it could simply be that they were given an overdose by the administers or that there was fault in the manufacturing process which led to there being higher than expected quantities of the drug.Since writing my (yes, sorry, rather long, even longer than I realised when I wrote that caveat) I've read up a bit on the news (or at least some of the reported facts, some that looked grossly wrong and some that seemed reasonable) and the fact that they appear to have a compromised immune system does look rather credibly attached to the immunosupprecancy 'feature' of the compound, so I'll perhaps back away from one of my first own pet theories that it was contamination of the 'buffer solution' that the drug was diluted into.

On the other hand, it might still represent a manufacturing problem from the POV of unintended isomer/polymer/close relative compounds leaking through the fabrication process.

One of the more horrifying ideas that I have imagined since my original post was the possibility of communication problem involving a comma/decimal mistake. The UK/US number 1,234.456 is written in European as 1.234,456 and it is conceivable (though I only mention it for completeness, not because I believe it is the case) that if instructions passed between one country and another (or even just between individuals on opposite sides of a partion) who natively employ the opposite methods of notation, then "disolve 1.000 nanograms of compound A per 1,000 ml [i.e. 1 litre] of saline solution" might well be interpreted as "disolve 1,000 nanograms [i.e. 10^-6 grames] per 1.000ml [i.e. 10^-3 literes] of saline solution", thus altering the concentration a million-fold.

One reason I doubt the (very specific) example above is that a million-fold increase in dose of a bio-active compound would (except for most benign of substances) would not just be "extremely bad for you" (as I would classify the incidents as actually suffered here) but fatal many, many times over without any hope of counter-treatment. But I mention it in a vain attempt to balance any undue (and unintended) bias I might have towards the "it wasn't really anyones fault, it just happened" that I might have. Simpler errors [I]have occured, and I was going to mention the 'comma/decmimal' one that destroyed the space-rocket, but on quickly checking that I wasn't talking complete rubbish I found the following debunking (http://rchrd.com/Misc-Texts/Famous_Fortran_Errors), which makes the analogy slightly less relevant than I had intended. Still, you could take my original intention in the spirit it was made, regardless of accuracy... ;)

Originally Posted by Valdania
Anyone think we should consider using prisoners (especially lifers) for drug trials like this?

If anything it would go some way towards meeting the costs of their incarceration.


no, just you I guess.... damn good thing too you inhumane bastard

Actually, the man's a genius. Something to use rapists for. Finally.

So, I guess it will take a little longer to get approved for general use?
Ok, I know this was a tragedy and all, but really there's no need to go over board with obviously over the top reactionary notions....it's just a minor set-back, we'll have the PR people work on it...maybe market it as a breast/penis enlargement drug since it seems it's anti-inflamatory properties may have been overestimated...:p