Drug trials do their job

One person is brain dead and five others are seriously ill after taking part in a drug trial for an unnamed pharmaceutical firm at a clinic in north-west France.

But wait!

The ministry did not say what the new medicine was intended to be used for, but a source close to the case told AFP that the drug was a painkiller containing cannabinoids, an active ingredient found in cannabis plants.

Cannabinoids cause brain death? Well, doesn’t that explain a lot of the 1960s then?

47 comments on “Drug trials do their job

  1. To have dropped six people–one fatally, this stuff must be a fairly powerful poison. How the fuck could that not be noticed before it was tried on humans?

  2. Real shame, but I suspect this will go down as “Fuck, couldn’t have predicted that…at least we know for next time” rather like thalidomide was.

  3. Maybe Ian–but most really poisonous stuff affects animals as well. In the case of dogs say–they can’t eat certain human foods without having severe internal damage–kidneys etc. But–the other way around I have never heard of something that it was ok for animals but so deadly to humans.

    Plus you would think they would start with a lowish dose so it must be a powerful poison even at small doses.

  4. This is why there are at least guidelines if not laws on dosing intervals in first-in-man trials (which, while we have not yet been told, this surely has to be). You will never eliminate occasional killing of the first person in to a first-in-man, but killing six is inexcusable.

    @SJW, the TGN problem was obvious to everyone except those who conducted the trial, that an AB raised against humans was going to cause effects in humans at a rather lower dose than in animals. Preclinical guidelines were amended in the light of it to take species-specificity into consideration. How a cannabinoid might do this is really bizzare because there are millenia of data on them. Other than the most likely FIM scenario, I suppose it could be a massive dosing error. It was oral but doesn’t say if pill or liquid.

  5. You will never eliminate occasional killing of the first person in to a first-in-man, but killing six is inexcusable.

    Who goes first?! Answering that question is maybe how they came to inject all at once. Does the first guy get paid more?

  6. But–the other way around I have never heard of something that it was ok for animals but so deadly to humans.

    You obviously haven’t tried my ex’s “sticky rice” then.

  7. “To have dropped six people–one fatally, this stuff must be a fairly powerful poison. How the fuck could that not be noticed before it was tried on humans?”

    The animal “models” are close, functionally often “identical” to our systems.
    They are, however, not identical to our complete metabolism, and this is where the risk lies.

    Makes me wonder if they’ve forgotten to do “pork trials”.
    Pigs are both genetically and with regards to metabolising Stuff our closest cousins. Something to do with encountering the same problems on basically the same natural diet, leading to the same, or similar-enough internal solutions.

    Pigs are more expensive than rats though, especially since you can’t sell the pork if you raise them for this purpose.

  8. Oh.. and “cannabinoid” is a group of chemicals, the natural forms of some of which are prevalent in various amounts in the Cannabis sativa cultivars.

    Much like heroïn is “simply” acetylated morphine, and crack modified dopamine, messing with Things may have rather profound side effects on the same metabolic pathway.

  9. Grickath – possibly the drug was intended for our lovely friends the representatives of the ROP community that have chosen to join us here in the old continent at this time, and pork testing was considered inappropriate…

  10. We don’t know the actual background of those affected.
    While blood tests and medical history get taken it does not mean all is known. Can be unrelated issue to the drug that causes this but then triggered by the drug.
    The individuals may have lied, ommitted or been unaware.

    Presumably they have something requiring such a drug?

  11. @Mr Tewman,
    You aren’t allowed to reimburse based on risk, only provide fair compensation for time, effort, and expenses.
    Someone always has to go first. Usually one person goes first on the lowest feasible dose, and you wait a few days before starting the next guy (yes, it is almost exclusively guys in Phase I). Starting 6 people at once is not normal. Usually the subjects will have no idea who is going first (they aren’t involved in the logistics), and even early trials are often blinded, so you don’t know who is really first.

    @Martin Davies, the participants in this case are all male, which is further indicative of a Phase I trial. In other words they are almost certainly all healthy volunteers and not patients in whom any form of efficacy analysis is being done.

  12. Grikath thank you for point out that cannabinioids weren’t involved. The article states earlier reports said they were but doesn’t state whether they were or not. The only reason I can think of for including this line is that it is likely to show up in searches.

    In my college days I did look into the trials being done thanks to the decent payout they gave. After reading the study I determined there was no way I was putting an untested drug into my body. At least some things haven’t changed in the last 2 decades.

  13. FIMs are usually done in young healthy people because they’re the least likely to die if you poison them. And they’re in men because young healthy women get pregnant – and you often would want to not have them taking artificial hormones, which makes the pregnancy much more likely.

    You want to do some tests in women at an early stage too because the hormonal environment is different enough that you can get drugs that kill women but not men.

  14. It looks like it was some kind of attempt at a synthetic cannabinoid. Because we don’t want people taking the real thing, because something something mumble mumble.

  15. If the Beeb is to be believed then Arnald is correct; it wasn’t a cannabinoid, but a synthetic chemical that bonded to endocannabinoid receptors.

    Again according to the Beeb, unlike the drug trials that went wrong a decade ago in north London, where the subjects became ill immediately after injection, these subjects appear to be reacting to a longer-term low dosage.

  16. Phase I, at least first-in-man (there are usually a lot of phase I trials done, not just one) is usually done in men because you know you are only exposing 1 person to the risk. OK, you don’t know know, because the guy may go home or to a nightclub and impregnate people, but the mere fact that only women might get pregnant gets them excluded from most of those trials.

    This is a really unusual situation given the multiple ascending dosing, it’s not the Tegenero problem from 10 years ago. It is clearly not the first trial. The only further speculation I will indulge in, as 5 of 6 people in 1 dose group got sick at about the same time, is a product quality issue. The media will anyway work faster than the internal rumor mill on this one.

    This, unfortunately, is why we do drug trials. It’s a tragedy for those involved will likely (and probably unjustly) do economic damage to the CRO that got given the trial, but for society it’s part of the cost of having new drugs.

  17. Or, men are considered more expendable.

    Also, I’ve just had a bunch of Proggies on Disqus explaining to me very forcibly that the unborn aren’t people; in fact they don’t exist at all. So it can’t be that.

  18. The Daily Mail, oddly enough, actually has a good write up on this. Some pretty nasty photos though.

    http://www.dailymail.co.uk/news/article-3400880/Serious-accident-trial-cannabis-based-painkiller-leaves-one-person-dead-five-hospitalised-France.html

    It also has this:

    http://www.dailymail.co.uk/health/article-3401329/Organs-registered-donors-taken-WITHOUT-relatives-consent-slash-number-patients-dying-transplant-list.html

    Grieving families will no longer be asked for their consent before organs are taken from registered donors, in major shift announced today.

    NHS chiefs in England hope the move will slash the number of cases in which bereaved relatives block vital organ donations.

    One in seven transplants from registered donors are currently vetoed by their next of kin – about 500 cases over the last five years, which is estimated to have deprived 1,200 patients lifesaving organs.

    Families still retain the right to block a transplant – but they will not be directly told this by medical staff.

    And if they do want to object, they must now do so in writing, providing their reasons.

    NHS Blood and Transplant expects the change to lead to a 9 per cent rise in donors.

    C*nts.

  19. dearieme – “If someone has registered as a donor, why in God’s name does his family have the power to overrule him? It’s his body, not theirs.”

    Because it is about dealing with grief. The dead are dead. What they want doesn’t really matter that much. The living on the other hand are still with us. And it is not a good look to pile on the suffering when they are already grieving by mutilating the body of their loved one.

  20. “Or, men are considered more expendable.”

    There’s that..

    The actual reason is that men have a stable hormonal balance throughout the month, and as such introduce far less extra factors into the tests, physically and psychologically.

    The only equivalent in a female is actually pregnancy. Which for obvious reasons also disqualifies them from playing guineapig.
    Their normal fertility cycle has a *massive* impact on their metabolism in many, many ways, making them pretty useless for getting consistent raw data.

  21. Incidentally.. If you wonder “but how about birth control then..?”

    Herr Eichmann and his staff were *very* meticulous, and their notes saved the pharma industry a lot of embarassing soul searching and controversy, given that the damage was already done.

    NASA is not the only one that got a boost from what the Troops brought Home.

  22. Because it is about dealing with grief. The dead are dead. What they want doesn’t really matter that much.

    It does, because we’re all going to be dead one day, and tend to care what happens to our bodies and our stuff afterwards. So if everyone ignores Granny’s wishes, that means they’re going to ignore yours as well. I cannot see any rational reason for my next of kin to be able to cancel my stated preferences.

  23. “The living on the other hand are still with us. And it is not a good look to pile on the suffering when they are already grieving by mutilating the body of their loved one.”

    That’s a feeble argument. The dead man doubtless considered it when he was alive, and rejected it. If you ignore the wishes expressed by the dead while they were alive, why do we honour wills or trusts? The corpse case sounds more like a surrender to sentimentality and superstition to me.

  24. dearieme:“If someone has registered as a donor, why in God’s name does his family have the power to overrule him? It’s his body, not theirs.”

    It’s your body while you’re still in it. Once dead, it technically ‘belongs’ to your next of kin.

    The NHS think it should belong to them. They can go take the sex and travel option.

    If that’s what they want, then lobby for a change in the law.

    Don’t deliberately lie by omission and place obstacles in the way of people asserting their rights.

  25. ‘Bial said it was committed to ensuring the wellbeing of test participants and was working with authorities to discover the cause of the injuries’

    Here’s a clue: it was the drug they took that caused the injuries.

  26. ‘But what about it caused the injuries?’

    Doesn’t matter. Test failed. The drug is dead. Research is over.

  27. I’m with dearieme on this one – if I can leave all my money to Battersea Dogs’ Home why can’t I leave my liver to science?
    [I haven’t left all my money to Battersea Dogs’ Home and my next-of-kin is fine with my leaving my heart to science although I suspect she has doubts about my liver]

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