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Rare reaction to new drug during trial.
March 16, 2006 6:11 PM   Subscribe

Newsfilter: The trial of a new drug to treat rheumatoid arthritis and leukaemia goes horribly wrong. 6 normally healthy volunteers have a freak reaction to the drug resulting in multiple organ failure. All 6 men are in intensive care. 4 are seriously ill while 2 remain in a critical condition. An eyewitness, fortunate to have taken only a placebo recalls the nightmare as the men around him begin to fall ill.
posted by piscatorius (98 comments total) 1 user marked this as a favorite

 
oh my God...and it never harmed any of the animals it was tested on?
posted by amberglow at 6:14 PM on March 16, 2006


oh my God...and it never harmed any of the animals it was tested on?

The drug had already been tested on animals and in a laboratory. I guessing it did not immediately kill all the animals otherwise they would not have moved on to human testing.
posted by Mr_Zero at 6:19 PM on March 16, 2006


i wonder if they skipped higher animals (like monkeys) or something? This is really rare. Are the standards high in Britain regarding testing? (i'd assume they were higher than they are here)
posted by amberglow at 6:27 PM on March 16, 2006


It's just so David Cronenberg and horrifying.
posted by johngoren at 6:32 PM on March 16, 2006


Hmmmm. What will the conservative spin on this be?.. Thanks to PETA...
posted by buzzman at 6:33 PM on March 16, 2006


There is a silver lining... a reaction that bad is likely to teach them something significant about human body chemistry that, unfortunately, they didn't already know.

Hopefully everyone will survive and recover well. What a lousy thing to have happen.
posted by Malor at 6:34 PM on March 16, 2006


newsfilter - hmmmm...
posted by RufusW at 6:35 PM on March 16, 2006


Boston Herald has more: ... Flanagan’s family, according to The Mirror of London, was told he couldn’t breathe, his head and neck had swollen to three times their normal size and his legs had turned purple. An otherwise “healthy young man,” Flanagan had seen the drug trial advertised on the Internet. ...
posted by amberglow at 6:44 PM on March 16, 2006


Researcher #1: "Well, as long as they've signed the indemnity papers, let's try injecting them with bleach!"
Researcher #2: "Dude, you are CRAZY@! haha! OMG, I can't believe they're letting us do this shit!"
posted by stavrogin at 6:46 PM on March 16, 2006


Less Freedom of Movement WITH Pain™
posted by hal9k at 6:49 PM on March 16, 2006


more: Drug trial ignored guideline on safety--DRUG trials that left six healthy volunteers fighting for their lives did not conform to best medical practice, The Times has been told.
Senior doctors expressed concern that all six were given the same dose of the experimental drug TGN1412 at the same time. According to the standard medical text, trials of this sort should avoid giving all the doses simultaneously. The Textbook of Pharmaceutical Medicine specifically gives warning that such practices can be “very difficult to manage” and “put subjects at unnecessary risk”.
...Last night the Medical and Healthcare Products Regulatory Agency was urgently investigating what went wrong in the the trials, as families kept up a vigil at the patients bedsides. It is trying to determine whether it was a fault in production, contamination or more likely an intrinsic problem with the drug itself. ...
There was confusion last night about whether the drug had been tested successfully on animals before the tests on human volunteers.
“They [the drugs company] said there was an oversensitivity in monkeys,” Ms Marshall said. She went on to say that in the tests a “dog and some animals had died . . . so they reduced the amount to humans”.
Thomas Hanke, chief scientific officer of TeGenero, last night refused at a press conference to say whether animals had died during earlier tests. “There has been no issue on the safety of the drug on animals. This is not relevant,” he said. He said the drug had been tested on mammals but not dogs or rats....

posted by amberglow at 6:50 PM on March 16, 2006


The BBC news service website quoted a lawyer for one family as saying that there is now some question as to whether any animal tests were conducted first.
posted by longsleeves at 6:51 PM on March 16, 2006


and, here at home: The Food and Drug Administration will let researchers test small amounts of experimental drugs on people at a much earlier stage than previously allowed, according to guidelines announced Thursday. ... (1/06)
posted by amberglow at 6:52 PM on March 16, 2006


It's nightmare stuff. One guy screaming that his head was about to explode, then later it expands to three times its normal size. I was having nightmares then - when I read his girlfriends in-depth description in The Times I was practically convulsing myself.
posted by fire&wings at 6:53 PM on March 16, 2006


I'm sorry, but if it kills higher animals, don't just lessen the dose and inject humans. Seriously. What a bunch of boneheads.
posted by davejay at 7:03 PM on March 16, 2006


There's going to be a lot of backpackers in London taking a long hard look at their finances now....
posted by pompomtom at 7:06 PM on March 16, 2006


It's rare for this kind of extreme reaction, but it's not at all rare for animal testing to indicate exactly the wrong reaction in humans.

Thalidomide. Aspirin. Saccharine. Vioxx. Those are only some of the the high-profile brand names, and most people aren't even aware of how they indicated exactly the opposite of the effect in humans.
posted by soyjoy at 7:15 PM on March 16, 2006


Three times normal sized head? That's pretty fucking big.
posted by sharksandwich at 7:20 PM on March 16, 2006


Pictures? Because yea, that's one big head. I just want to see it.
posted by kjell at 7:37 PM on March 16, 2006


science dude explains what they took (audio)
posted by dydecker at 7:50 PM on March 16, 2006


I wouldn't be surprised if the researchers/drug company fudged the results of their animal tests -- if there even was much animal testing.

And regarding thalidomide, a quick search seems to indicate that the "proper tests" on animals weren't conducted.

One could cut the drug company some slack, if they did everything they should have in the animal testing phase and then this nightmare occurred. But if the testing was inadequate or they misrepresented things in a rush to get the drug to market, then throw the book at them IMHO.
posted by bim at 7:52 PM on March 16, 2006


Not that it will do any good, but it might be cathartic...

http://www.parexel.com/contact/contact_us.asp

http://investor.parexel.com/ireye/ir_site.zhtml?ticker=prxl&script=2300
posted by ryanhealy at 7:55 PM on March 16, 2006


Three times normal sized head? That's pretty fucking big.

Can you imagine if you were on mushrooms and this guy walks in?
posted by Mr_Zero at 8:00 PM on March 16, 2006


Jesus, it's absolutely amazing that this could have happened with animal testing. There must be something very different about human philology that caused this to happen (or a mistake with the drug itself).

Oh well, goes to show why animal testing is so important.
posted by delmoi at 8:02 PM on March 16, 2006


Can you imagine if you were on mushrooms and this guy walks in?

I can.

Whoa.
posted by delmoi at 8:03 PM on March 16, 2006


Hmm, it's only down $1.62 on Nasdaq. Should be a busy day tommorow.
posted by delmoi at 8:04 PM on March 16, 2006


But what was the drug?

/Works in purification of a certain biopharmaceutical, currently in clinical tries worldwide for rheumatoid arthritis and leukemia (among other things)
posted by iamck at 8:20 PM on March 16, 2006


Ah, TeGenero AG. Not the German company I work for.
posted by iamck at 8:21 PM on March 16, 2006


I really should not have read the Wikipedia article on Thalidomide. I hate being retroactively furious incensed livid at things I can't change.

If it comes out that the scientists faked data or otherwise intentionally massaged their results, they should be tried and hopefully convicted for attempted manslaughter. Not only is this a horrible human disaster, but it is a crime against the nature of science and progress.
posted by Skorgu at 8:33 PM on March 16, 2006


Wow. In related news, eleven die in another drug trial for another drug company. How often does this kind of thing happen?
posted by zsazsa at 8:51 PM on March 16, 2006 [1 favorite]


a good thing from the new Guardian thing: ...the lesson from Northwick Park is that we are all about to take part in a psychological and ethical trial: forced either towards a greater acceptance of the deaths of patients with chronic conditions, or a higher tolerance of something (more animal testing) or someone (triallists in the developing world) having to die to extend our lives.
And, while it can be no consolation for the families involved in this tragedy, one beneficial consequence might be reduced media enthusiasm for the idea of the "miracle" pill.

posted by amberglow at 8:56 PM on March 16, 2006


Ahhh, prescription drugs. In which everything one would have taken an illicit though often natural drug for now has a replacement. Only with side effects. Like elephantitis, for example. But, of course...legally!

*takes a hit for those who don't realize or are never told that the cures come from the Earth, and that conversely: When you fuck Ma Nature, she fucks you back. Hard. With no Vaseline.*
posted by rollbiz at 8:58 PM on March 16, 2006


Hippies are so cute!
posted by mr_crash_davis at 9:06 PM on March 16, 2006


Very much not a hippie, in case that was directed at me mr_crash. But have it your way. Tell me with a straight face that you think that the (legal) drug industry has our best interests in mind, and has created solutions on par which those drugs which are considered illicit, and then call me a hippy all you'd like, if this was in fact your original intention.
posted by rollbiz at 9:11 PM on March 16, 2006


on par *with* those drugs. Sorry, call it a hippie moment.
posted by rollbiz at 9:15 PM on March 16, 2006


delmoi:
There must be something very different about human philology that caused this to happen (or a mistake with the drug itself).

Sure, blame it on the linguists, why don't you!

sorry
posted by greatgefilte at 9:20 PM on March 16, 2006


In which everything one would have taken an illicit though often natural drug for now has a replacement.

i just want to add that those natural drugs didnt come for free. All the herbal remedies we know of, the poisonous plants we know - of came because they were discovered to be so by some other humans in the historical past. There were lots of deaths to get that information - deaths by accident, deaths of captured prisoners - in order for that information to be passed down through human history. Human trials is the oldest and most efficient form of learning we have had. We can do better but lets not idealize that which is "natural"
posted by vacapinta at 9:23 PM on March 16, 2006


Hippies are so cute!

You'd have to have seen some oldish pics of m_c_d to fully enjoy the irony here (or did I just dream of Sasquatch Davis?).
posted by stavrosthewonderchicken at 9:28 PM on March 16, 2006


Ah, natural remedies. Nothing sends a brain tumor into remission like a nice hot cup of echinacea tea.
posted by the jam at 9:35 PM on March 16, 2006


Shhhh, stav. Keep it on the down-low, would ya?
posted by mr_crash_davis at 9:37 PM on March 16, 2006


Tell me with a straight face that you think that the (legal) drug industry has our best interests in mind, and has created solutions on par which those drugs which are considered illicit...

There is a lot of bullshit involved in the pharmaceutical industry - it's part of a market driven approach to helping people. But that's a bit of a knee jerk overexaggeration to declare all drug manufacturers as *evil*. As someone who needs to take prescription drugs everyday to control chronic illness of which there would be not natural substance, I know the benefit of pharmaceuticals.
posted by iamck at 9:48 PM on March 16, 2006


It's that money and a rush to market often takes precedence over safety, and that government watchdogs aren't watching at all, but changing the rules to make it even easier to just push things thru without proper testing.
posted by amberglow at 9:59 PM on March 16, 2006


Hmm, plugging TGN1412 (or TGN 1412) into PubMed doesn't pull up anything.

Anyone know what this is and what it's (purported) method of action?
posted by PurplePorpoise at 10:06 PM on March 16, 2006


Effective, safe, cheap. Pick two.
posted by aberrant at 10:06 PM on March 16, 2006


vacapinta,-I'd really like some substantiation to our comment.

iamck- I'm not knocking anyone who has found a sucessfull method of treating anything. I'm merely questioning the market driven pushing of prescription and OTC drugs. I don't know about you, but the drug industry really frightens me in terms of their lobby and advertising dollars. I get the feeling you don't concur, but what I'm really asking is (as one example): What do you think the reception would be for a prescription pot ad? In terms of medical study or otherwise, I don't think marijuana has ever been shown to cause the grevious medical issues we're talking about now, and yet I feel the opposition would be similar to that of this drug which has damn near killed all who have taken it.

Point being again, if you fuck Ma Nature she is coming back for her dues. That is all.
posted by rollbiz at 10:20 PM on March 16, 2006


rollbiz:
Point being again, if you fuck Ma Nature she is coming back for her dues. That is all.

What does that mean, really? I'm not being sarcastic - I really don't know what you're on about.
posted by aberrant at 10:25 PM on March 16, 2006


PurplePorpoise... If you google that, you'll find a link to the companies page about the product, which they call "The company’s most advanced product candidate TGN1412"

I'm afraid of their less advanced product. I'm sure you'll find much more info on that page and from a simple google search.
posted by symbioid at 10:28 PM on March 16, 2006


the drug lobby is a powerful and dangerous thing It is insane to allow them to control our drug policies and ethical standards.

Yet more and more, we do.

We need to make better use of our democracy.
posted by five fresh fish at 10:29 PM on March 16, 2006


Hey, could someone spot me a capital and a period? I seem to be coming up short.
posted by five fresh fish at 10:29 PM on March 16, 2006


In which everything one would have taken an illicit though often natural drug for now has a replacement. Only with side effects.

Because natural things from the bosom of mother nature, such as ricin, botulinum, taxol, nicotine, digitalis, nightshade, hemlock, and cobra venom, don't have side effects.
posted by ROU_Xenophobe at 10:33 PM on March 16, 2006


Also, this page indicates it was approved through EU Orphan Drug procedures...
posted by symbioid at 10:35 PM on March 16, 2006


Hey, could someone spot me a capital and a period?

All I've got is a triple exclamation point and this slightly bent circumflex. Can you use either of those?
posted by stavrosthewonderchicken at 10:35 PM on March 16, 2006


fff: not disagreeing with you, necessarily, but who would you have as a monitor?
posted by aberrant at 10:41 PM on March 16, 2006


Here stav, let me straighten out that circumflex for you.
posted by Cranberry at 10:47 PM on March 16, 2006


Ah, thanks symbioid - I didn't think that a drug company would actually tell the public what their drugs did.

CD28-MAB? Sounds suspiciously like a monoclonal antibody (or something akin to it; if not something even stronger than an stimulating monoclonal) to CD28 (a receptor on T cells; T cells can directly kill target cells that they recognize) which is a trigger telling the T cell to get it on!!1!!one!!!1!

(Stimulating the B cell chronic lymphocytic leukaemia cells directly to make them better antigen presenting cells is a far more sane approach)

I'm kind of not surprised to not find any peer-reviewed papers on this drug.

Randomly activating T cells - sure, you might activate some that have a rearranged receptor that will recognize and kill leukaemia cells - but fuck, you're asking for trouble by activating any T cell that comes into contact with this stuff.

The analogy (providing CD28-MAB is what I think it is) - soldiers in an urban area trying to eliminate insurgents. Some soldiers know what an insurgent looks like, some soldiers know what a civilian looks like, and other soldiers know what soldiers looks like. Ideally, you'll activate the soldiers that recognize insurgents. Something like this will activate all soldiers regardless of who their target is.

As for rheumatoid arthritis, I have no idea how activating T cells would stop B cells from producing autoantibodies aside from that chronic overstimulation of T cells will induce them to either/or 1) surrender and produce anti-inflammatory cytokines (small protein signals) 2) give up and die (activation induced cell death).

From the newspaper article (if it's accurate), it sounds like someone decided to give these test volunteers a huge bolus of this stuff and 6 out of 6 (aside from the 2 given placebo) developed serious immune activation symptoms.

Someone fucked up big time.

As for the test animals, if CD28-MAB is what I think it is (something that acts as a "superantigen" but with CD28 as it's target) then I suspect that it may be far more potent against human CD28 compared to mouse or chimp CD28 (the shapes of the related molecules are slightly different between species).
posted by PurplePorpoise at 10:53 PM on March 16, 2006


Can you imagine if you were on mushrooms and this guy walks in?

Giant heads. Mother Nature fucking people for dues. The whole conversation is giving me acid flashbacks.
posted by onegreeneye at 10:55 PM on March 16, 2006


Oh, right - normal cell surface molecule interactions are more along the lines of "tickling" or "shaking hands" to induce the receptor molecule to make things happen. A superantigen gloms onto the receptor and essentially dry humps it like a frat boy on ecstacy and viagra.
posted by PurplePorpoise at 11:03 PM on March 16, 2006


aberrant: oh, lessee. how about a panel of impartial ethicists? scientists? experts we can pay to come up with answers we can trust?

Or we could, you know, continue to let corporations control our health and safety. They're reknown for their compassion and integrity.
posted by five fresh fish at 11:10 PM on March 16, 2006


fff: who's "we"? Again, I'm not trying to be argumentative (and your sarcasm isn't helpful, frankly). I'd like to hear more about your alternative.

Another question: would you be willing to pay more for your medication to support this panel of experts? (And who decides membership?)
posted by aberrant at 11:15 PM on March 16, 2006


I'm kind of not surprised to not find any peer-reviewed papers on this drug.
TeGenero has been referring to it by the tradename CD28-SuperMAB in the literature rather than the internal name TGN1412. The method-of-action is novel and TGN1412 was granted orphan drug status in Europe for a certain type of leukema indication.

oh, lessee. how about a panel of impartial ethicists? scientists? experts we can pay to come up with answers we can trust?
At the government regulatory level, it's called the FDA. Its counterpart in Europe is the EMEA. Within the hospital (where trials usually take place), it's called the Institutional Review Board (IRB). Now if you're proposing that some type of independent group be formed to travel around the globe all the time to poke and scrutinize at every single clinical trial that's taking place anywhere, then you should be prepared for drug development to take place at half the speed it does now.

amberglow: When you're suffering from a debilitating disease and the promise of a new treatment is around the corner, then drug development is occurring too slow and there's too much regulation. When you're healthy and reading about people who are getting sick in clinical trials, then drug development is occurring too quickly and there's not enough regulation.

The claims of successful animal testing seem shaky and TeGenero's publications only extend to rat testing. And while the medical textbook says doses shouldn't be given simultaneously, the VP of Toxicology at another major CRO, Covance UK, said the practice was normal. I don't deny the possibility that TeGenero or Parexel may be at fault for this. However, painting a broad black swath on the entire industry because of this tragedy seems irresponsible.
posted by junesix at 12:38 AM on March 17, 2006


I'd just like to say that these big pharma companies aren't scum - or at the very least, among corporations they aren't any particular kind of scum. They're in it for the money. But what brings the money? A successful drug, moderately priced, for a large market. They can't sell a shitty product, and when they do, it can't be too expensive or insurance companies won't pay for it, and it can't be for too small a market because there's no profit margin in small-time manufacturing. So, they're in it for the bottom line, but it's in their interest to produce a good product - which means we are in their interest, indirectly of course but we're there.

That said, this was obviously a monumental fuck-up and whoever was responsible should be charged with criminal negligence and a bunch of other stuff.
posted by BlackLeotardFront at 12:55 AM on March 17, 2006


In the past year I've been doing clinical trials myself (with my job I gots lotsa time off, perhaps too much). With one medicine I actually got nauseated for about 20 minutes but that was about it.

Good thing I get a shitload of money for those things.
posted by zardoz at 1:17 AM on March 17, 2006


Maybe they should divert some money from marketing to their research department:

The marketing budgets of the drug industry are enormous -- much larger than the research and development costs -- although exact figures are difficult to come by, in part because marketing and administrative expenses are often folded together and in part because some of the research and development budget is for marketing research.

According to its annual report, Pfizer spent 39.2 percent of its revenues on marketing and administration in 1999 (16); Pharmacia & Upjohn is reported to have spent about the same. (12) The industry depicts these huge expenditures as serving an educational function. It contends that doctors and the public learn about new and useful drugs in this way. Unfortunately, many doctors do indeed rely on drug-company representatives and promotional materials to learn about new drugs, and much of the public learns from direct-to-consumer advertising. (17) But to rely on the drug companies for unbiased evaluations of their products makes about as much sense as relying on beer companies to teach us about alcoholism.
posted by moonbiter at 1:35 AM on March 17, 2006


Amazingly it has raised the profile of cash for guinea pigs.
posted by srboisvert at 3:52 AM on March 17, 2006


Thanks for the excellent explanation, PurplePorpoise.
posted by Civil_Disobedient at 4:05 AM on March 17, 2006


Tell me with a straight face that you think that the (legal) drug industry has our best interests in mind...

Don't talk to me, talk to Mr Potatohead two beds down.

posted by hal9k at 4:09 AM on March 17, 2006


junesix wrote:
  • And while the medical textbook says doses shouldn't be given simultaneously,
  • the VP of Toxicology at another major CRO, Covance UK, said the practice was normal.
  • However, painting a broad black swath on the entire industry because of this tragedy seems irresponsible.

  • Clearly!
    posted by ryanrs at 4:32 AM on March 17, 2006


    While I do suspect that somebody didn't do what they were supposed to do in this latest trial, I don't see that as an indictment of every drug company -- and the value of prescription drugs.

    Without things like cholesterol lowering drugs (yup, count me in on that), drugs to lower high blood pressure, heart medications and a million other things, people would lose their lives a lot quicker than one might hope (or live less comfortable lives). And don't tell me to take the hippie dippie "natural" route. There's no way you're going to sufficiently reduce a cholesterol count of 313 without prescription drugs. Been there, done that. A lot of it is just bad genes.

    Or we could, you know, continue to let corporations control our health and safety. They're reknown for their compassion and integrity.

    Come on...get real. Do we want the government responsible for developing all prescription drugs? George Bush and Company (they've already turned energy policy over to the oil companies) or any administration for that matter? The same folks who can't find their rear-ends with both hands and a flashlight? No, thanks. I'll roll the dice with the current system and heavily penalize those who don't follow the rules.

    I'm a realist. I don't expect drug companies to be altruistic. There's nothing wrong with folks doing something to make a profit. The drug company benefit and people benefit from the development of good drugs. But I do expect them not to be NEGLIGENT. That's a different matter entirely.

    Everything is a matter of degree.
    posted by bim at 4:32 AM on March 17, 2006


    And regarding thalidomide, a quick search seems to indicate that the "proper tests" on animals weren't conducted.

    True, but then again, full lifecycle testing on animals wasn't very common anyway. The Thalidomide tragedy brought that to the fore. Thailidomide is a safe sedative (not that we really need that), is a lifesaver in the case of Hansen's Disease, and seriously improves the life (and longevity) of those with multiple myeloma. But it's a disaster to an unborn child.

    I'm reminded of thalidomide by this. I also recall the protests against the FDA for being slow in approving various AIDS treatments, esp. AZT.

    Which is better? Rapid testing cycles, which are much riskier to the test population and to the first patients, or careful testing cycles, which may leave sufferers without treatment for an extended time?

    I won't even begin to pretend I have a pat answer for that one.
    posted by eriko at 5:11 AM on March 17, 2006


    Actually, I see nothing wrong in using Thalidomide to benefit AIDS patients (if studies merit it). I recall reading about the hue and cry to prevent Thalidomide from coming back on the market as an AIDS drug because of the earlier problems with birth deformities.

    A lot of folks seem to see everything in black and white terms -- unfortunately. You'd think that as they get older they would realize that most things involve "shades of gray."

    And if I see one more overly simplistic law being passed and being called Tom' Law, Dick's law or Harry's Law, I'll scream!
    posted by bim at 5:31 AM on March 17, 2006


    sharksandwich : "Three times normal sized head? That's pretty fucking big."

    Dunno how they measured it, but if it's three times the volume, that means each dimension (width, height, and depth) were 1.44 times normal size...Which is still huge.
    posted by Bugbread at 5:35 AM on March 17, 2006


    There was a hepatitis B drug in the early 90s called FIAU that had about the same record. I found this site, which transplants a Washington Post story about it (although I find Dr. Mercola's bolding to pretty annoying).
    Also had limbs swelling up to double the size because of kidney shutdown. The NEJM abstract on it is here.
    posted by dances_with_sneetches at 5:37 AM on March 17, 2006


    I remember a similar problem when they were testing Ephemerol up in Canada. Much like Thalidomide it affected changes in the unborn foetus. These changes took on varying degrees of what some may call birth defects. A small group of children of the first test subjects seemed to be more greatly affected than children born later after they reduced the dose given to pregnant women. Ephemerol, if I recall correctly was intended to relieve morning sickness. It was pulled off the market shortly after the second round of birth defects was discovered. However by that time, like Thalidomide, Ephemerol's developers had found alternative uses for the drug. One of which was described as a treatment for those suffering the aftermath of their mother's having taken the drug. I believe a documentary was made about the testing and the children whose lives were changed by the drug.
    posted by Gungho at 6:30 AM on March 17, 2006


    Good finding amberglow !

    Senior doctors expressed concern that all six were given the same dose of the experimental drug TGN1412 at the same time. According to the standard medical text, trials of this sort should avoid giving all the doses simultaneously.

    and junesix too

    And while the medical textbook says doses shouldn't be given simultaneously, the VP of Toxicology at another major CRO, Covance UK, said the practice was normal.

    Ummmh there's something wrong and indeed

    That could have been avoided, she said, if at the start only one of the volunteers had been given the drug.


    Which is pretty fucking obvious, if you ask me. Why try unknown drug with six person, why wasn't the risk reduced ? We get an hint of why

    However, Chris Springall of Covance Clinical Research, a company based in Yorkshire that carries out drug trials, said that the practice by which the whole group was given a dose at the same time was normal in the industry. But it was not considered risky because side-effects were so extremely rare.

    Bingo, here's the problem. It's the didnt-happen-in-the-past, therefore we can reduce safeties logical fallacy. Such kind of
    pressure to reduce time-to-market is very likely to come from a company and it's pure insanity. People are going to die because
    of this, because somebody is oooohh so worried about giving us what we want at any cost as long as its not a company cost.

    Also it seems that the adverse reaction very quickly showed itself, so no particularly intolerable delay was going to be introduced by trying only with ONE volounteer.
    posted by elpapacito at 6:48 AM on March 17, 2006


    Jesus, it's absolutely amazing that this could have happened with animal testing.

    Uh, yeah. It's "absolutely amazing" every time something like this happens. Which is apparently much more often than you realize. You might want to look into it.

    Oh well, goes to show why animal testing is so important.

    Hilarious. This sounds exactly like Bush logic: "The public reaction to the ongoing disaster in Iraq just shows how important it is for us to put on a happy face and keep lying to them."
    posted by soyjoy at 6:56 AM on March 17, 2006


    What eriko said about pressure from AIDS groups, to shorten the time to get drugs to those who need them. And the victory claimed by those groups when the FDA heard and responded.

    Surely in these days of viagra, we see the drug companies as marketing maniacs. But every drug isn't like that. And marketing prescription drugs is, in large part, paying highly for well educated people to go talk to busy doctors. That's a marketing technic that's bound to be damn costly.

    I'm not even remotely interested in painting drug companies with some broad brush over the negligence of one testing outfit. Drugs work. Drugs save lives. Drugs are created/discovered in expensive labs. Albert Hoffman didn't work in his garage.

    One thing, this is surely going to make it harder to recruit subjects for human trials! Probably it should. Of course, some people will still do it for the money. Especially those struggling to pay for school, or possibly medical care for a loved one.
    posted by Goofyy at 7:04 AM on March 17, 2006


    Thank you, soyjoy, I noticed the same strange logic.
    posted by agregoli at 7:11 AM on March 17, 2006


    Strangely enough, Gungho, I just rewatched that documentary last night. Nosebleeds, earaches, stomach cramps, nausea, sometimes other symptoms of a similar nature. Biocarbon Amalgamate is rightly not around anymore.
    posted by Hubajube at 7:14 AM on March 17, 2006


    Randomly activating T cells - sure, you might activate some that have a rearranged receptor that will recognize and kill leukaemia cells - but fuck, you're asking for trouble by activating any T cell that comes into contact with this stuff.

    Yeah, reading the product page made it seem much less surprising.

    I know enough about biology to know that they were A) fucking around with the immune system and B) Leukemia is a cancer and cancers are caused by human cells which means these guys were some how trying to get the human immune system to attack human cells, but only cancer cells and also 'inflamed' cells!?

    That's crazy, and the immune system is something that evolves very fast, so there would be a much greater difference between a human immune system and a mouse's, while a human and rat neural structure are so similar that anti-depressants work almost the same way in humans and rats.

    The reaction also sounds like an allergic reaction. And if the drug triggered some sort of auto-immune disease, well, that would really suck.
    posted by delmoi at 7:17 AM on March 17, 2006


    skipped the comments on this, but errors in drugs trials aren't uncommon. In Alabama, where a lot of FDA trials happen, a pharm company decided to test a "less addictive" form of morphine as a pain killer. the clinical trial nurses choose some back surgery patients for the trial and the ones given a placebo went into shock (naturally) becuase they had just had back surgery and now we're deprived of pain killers.
    posted by aljones15 at 7:18 AM on March 17, 2006


    I remember a similar problem when they were testing Ephemerol up in Canada

    Was this about the same time that the mining industry had problems with polydichloric euthimal?
    posted by ROU_Xenophobe at 7:27 AM on March 17, 2006


    More:

    "Drug trial horror patient may be in coma for a year."

    "Leukaemia drug test disaster 'will put off volunteers':
    (...)
    Mr Sturge predicted the impact on volunteers of the trial of the drug, known as TGN1412, at Northwick Park Hospital, Middlesex, would be only short term.

    But he added that the dramatic events - which led to one volunteer's head swelling up to three times its size and another volunteer becoming so disfigured his girlfriend called him the "Elephant Man" - underlined the importance of animal testing."
    posted by iviken at 7:32 AM on March 17, 2006


    Maybe they should divert some money from marketing to their research department:

    I keep hearing this argument, but I've never understood it. If pharmaceutical companies took money away from their marketing budgets for R&D, then the next year they would make less money total. Then they'd have less money for R&D and for marketing, and each year they would have less and less money, until their market share normalizes with their new marketing level.

    There's obviously a point of diminishing returns on marketing, but if you're not there, cutting back on your marketing budget means you'll lose money quick.

    Telling Pharma companies to spend less money on advertising is like telling trucking companies to spend less money on gas.

    Amazingly it has raised the profile of cash for guinea pigs.

    hmmm
    "This has brought medical trials to the forefront," he said. "There are loads of people out there willing to participate who will be introduced to medical research one way or the other. That's what's taking place right now."
    ...
    "It's unheard of, what's happening. But whether it lasts one week or two weeks, or one month or two months, there's no telling," he said. "I guess it depends on whether the volunteers live."

    Wow, I'd heard the brits had a dry sense of humor, but that was a bit unexpected. (of course, I suppose he's talking about the 6 injured men, not the people he's recruiting)
    posted by delmoi at 7:50 AM on March 17, 2006


    the clinical trial nurses choose some back surgery patients for the trial and the ones given a placebo went into shock (naturally) becuase they had just had back surgery and now we're deprived of pain killers.

    Oh my god...
    posted by delmoi at 7:51 AM on March 17, 2006


    Just awful. I hope they come through alright. I wonder if there are going to be long-term problems if they do. I also wonder what the drug company will do for them.
    posted by Alpenglow at 7:57 AM on March 17, 2006


    I'm reminded of thalidomide by this. I also recall the protests against the FDA for being slow in approving various AIDS treatments, esp. AZT.
    Which is better? Rapid testing cycles, which are much riskier to the test population and to the first patients, or careful testing cycles, which may leave sufferers without treatment for an extended time?

    I know--i protested for faster approval of AIDS drugs back then, but AIDS was a certain death sentence, and there were no other options at all, like the drug cocktails that are now available, etc--and even those don't work for all. It's a problem--i'd like to see more animal testing rather than more people testing--unless the early people testing is only with volunteers who actually have the disease. That's what people were agitating for--many back then would have gladly been the guinea pigs--most, i think.

    This testing on people without the diseases to be helped by the drug is what needs more oversight by some sort of regulatory agency, not the drug approval in itself, i think.
    posted by amberglow at 8:28 AM on March 17, 2006


    I can't find a link for it, but a spokesman for the company on C4 news last night said that the dosage given to the men was 1/500th of what they believed to be a normal dose.

    Imagine how big their heads would have been then.
    posted by ciderwoman at 8:32 AM on March 17, 2006


    I do want to add that many believed the AIDS drugs were purposely being not reviewed or approved, and not pushed for, and they weren't. Look at what happened with the Plan B/Morning After stuff. The FDA is a political organization--not medical, and is affected by whoever is put in charge and put on the board. The current crop of people there now are horrible.
    posted by amberglow at 8:40 AM on March 17, 2006


    CNN is reporting eleven deaths in the Phase 3 human trial of Aircept for a kind of vascular dementia, different from the Alzheimer's type of dementia the drug was originally approved to treat in the mid-90's. This is relevant to this discussion because it illustrates that even a drug which has passed clinical trials and has been in use for years, may still have significant toxicity issues in larger populations, or when given to people with differing conditions than what it has already been approved to treat.

    There are no absolutely "safe" drugs, and the whole idea of medicine, in any form, is the mitigation of certain pain or death by administration of some therapy with an acceptable degree of risk, to correct or offset the known problems of the disease or disability being treated. Personally, I think informed consent of the persons to be treated, and deference to their risk willingness, is the best treatment policy in most cases. But absent the kinds of ethically conducted scientific studies which can provide useful statistics and contraindication and mortality risk information, "treatment" of later patients is not possible.

    What I think needs to be in place is a risk pooling mechanism from which ongoing care and/or long term restitution to trial volunteers and/or their families and estates can be paid, should something as awful of these results happen. That's lacking in the present Western system, and is arguably, I believe, a quasi-governmental function, or at least something that needs specific legislative authorization and encouragement to come into existence.
    posted by paulsc at 8:47 AM on March 17, 2006


    In Britain, is the regulatory agency hands-off and reliant on the data supplied by the drug companies as they are here? I don't think the FDA even knows all the facts about trials while they're happening--they just approve the starting of the different phases, analyze the results, and give approval or not.

    And, as with Vioxx, many people died even after it was fully approved (10 members of the FDA panel had ties to the company), and on the market, for it to be withdrawn, while other drugs never see the light of day.
    posted by amberglow at 8:56 AM on March 17, 2006


    aberrant: who's "we"?

    We, the people. Who elect governments presumably to perform those functions that we require yet can not perform as mere individuals.

    I'm keen to hear why you appear to think that either everything is peachy with the current regulatory bodies, or think that we should let the corporations make those decisions for us.

    I honestly don't see many alternatives to the application of consumer-oriented, independent oversight of the healthcare industry.
    posted by five fresh fish at 9:09 AM on March 17, 2006


    The 11 deaths for Aricept is out of 650 for 24 weeks who were taking it for vascular dementia/Alzheimer's. This is probably a group that averages 80 years of age. While it is mentioned that it is statistically significant higher death rate than placebo, I imagine several of the placebo patients died because of the age range.
    Aricept is a kind of sucky drug though. Little benefit, lots of adverse effects (although death is not usually listed among them).
    posted by dances_with_sneetches at 9:09 AM on March 17, 2006


    And as for funding, let's say we take 1% of the marketing budget from each of the big ten pharmas. That's enough money to not only completely fund a panel of experts, but enough to make damn sure the trials themselves have ethical overseers.

    Honest to god, you act as though this is some sort of challenging mystery. It isn't. It just takes the balls and brains to do it. Something our governments lack.
    posted by five fresh fish at 9:15 AM on March 17, 2006


    If pharmaceutical companies took money away from their marketing budgets for R&D, then the next year they would make less money total.

    Not necessarily so Delmoi.

    Then they'd have less money for R&D and for marketing, and each year they would have less and less money, until their market share normalizes with their new marketing level.

    What you are describing is what would happen if reduction of investment in marketing caused a proportional reduction in sales, but it isn't necessarily so direct a connection. While it's possible and likely that a reduction of sales will occour, if the product has intrinsic qualities and if the initial investment was significant enough to have doctors know and recommend the product, then a reduction of advertisement will not affect sales significantly.

    Why ? Simply because no doctors like to prescribe a new medicine if the old ones works well, because it's tried and tested and reliable. Why put patients and their practice at risk ?

    So what happens is that the money isn't spent to "inform" more doctors or to convince them of the superiority of Drug XYZ, but it is spent to simply corrupt them. What about a travel to Hawaii to learn about something ? It is 2 hours a day of learning at 22 hours of fun ! All kinds of fringe benefits reach either them or their relatives , so that the doctor is encorauged to prescribe.

    From an economical point of view that's financing a sale by throwing money to the problem that the market is saturated with products that are good enough, so big companies with big reserves of money try to strangle generic-drug competitors by patent and by marketing, both of which do NOT increase the benefit to consumers or make the drug accessible to less rich people.

    Yet even if people is not entitled to better products (they should well do that themselves) they certainly shouldn't carry the burned of corruption of doctors nor the burden of competition between companies (a burden they already carry by work uncertainity and destruction of the concept of retirement and financial safety)
    posted by elpapacito at 9:23 AM on March 17, 2006


    Why ? Simply because no doctors like to prescribe a new medicine if the old ones works well, because it's tried and tested and reliable. Why put patients and their practice at risk

    The issue is NOT one of why prescribe (1) drug A which is new and untested, as opposed to (2) drug B which does exactly the same thing in the same way and yet is older and more reliable.

    Take cholesterol drugs as an example. I've been through several. Some folks don't like the side effects that occur with certain drugs. I hated Lipitor (made me very tired). Somebody else developed a new cholesterol drug that does a good job of lowering cholesterol with fewer or no side effects (Vytorin) -- which I take and much prefer. IMHO, that's a good thing and I'm glad a drug company made yet another cholesterol reducing drug. Now there made be some older and well known drugs out there, but everybody is different. Not everyone can comfortably use that older drug.


    From an economical point of view that's financing a sale by throwing money to the problem that the market is saturated with products that are good enough...

    Wrong. Where did you get this revelation? See my previous point.


    ...so big companies with big reserves of money try to strangle generic-drug competitors by patent...

    Finally, something we agree on. The folks who do R&D do deserve a return on their investment. They seem to think that return should last into perpetuity -- which is crazy.


    ...they certainly shouldn't carry the burned of corruption of doctors...

    Actually, I like my doctor. He's always done right by me and he doesn't seem to be getting filthy rich. He's just making a living like everyone else. Let's not paint everything with such broad strokes, eh?
    posted by bim at 5:36 PM on March 17, 2006


    Huh. I was all set to be a subject for a clinical trial - this has been in the works for months now - and tonight I got an e-mail that due to a previous subject's adverse reaction, the trial is off. And I'll be paid five hundred bucks.

    There was something off about this before, sufficiently so that I posted about it on askMe last year. http://ask.metafilter.com/mefi/25561
    posted by goofyfoot at 11:58 PM on March 17, 2006


    ...However, evidence passed to The Observer shows the company earlier planned to use cancer patients, which would have been more in line with standard practice because of the risks involved with the antibody drug.
    In an interview with The Observer, Hanke said: 'We are devastated by the tragic events that have happened. We are terribly sorry it went so wrong.' But he defended the trial: 'With a toxic drug you start with patients right away, particularly cancer patients. But with a drug where you don't assume there are side effects there is no reason not to use healthy volunteers.' ...

    posted by amberglow at 8:58 AM on March 19, 2006


    You'd think cancer patients would have enough to deal with, without being turned into a real-life Violet Beauregarde.
    posted by five fresh fish at 11:34 AM on March 19, 2006


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