Placebos

jryans10

jryans10

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Hi all,

I was watching a horror film last night about this pharmaceutical trial (clinical trial), and it got me thinking, why do they have placebos?

The only information I can find online is that so they can see how normal people act, but if this is the case, why not just bring in a normal person and not give them anything at all?

Thanks, sorry for my ignorance! :bonk:

PS - Film was called "The Last Experiment" if anyone is interested :) - quite a silly film though I must say.
 
Because people can exhibit a response (of sorts), or will report a subjective response, simply because they believe they are receiving a treatment - regardless of whether or not the treatment works. This is called a "placebo effect". So a sham or ineffective treatment will work - or appear to work (an important distinction) - better than nothing at all.

Therefore, in order to determine whether your drug is actually doing something real (i.e. isn't just a placebo itself), you need to compare what happens with the drug against what happens to a patient with the same condition who is treated with a placebo (ideally the patient's experience of the administration of the placebo is exactly the same as if it was the real drug - if you inject the drug, you inject the placebo, for example; in this case the placebo would usually just be saline). Importantly, the patients do not know whether they are receiving the placebo or the experimental drug.

Does that make sense?
 
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Because if someone thinks they're taking something that will have a particular effect they may think the effects are real.

For example, if someone has a headache and you give them a tablet and tell them it's the most powerful anti-headache table ever (even though it's got no pain relief properties at all) it's possible they'll think themselves into having no headache.

I bit like a kid who falls over, hurts themselves but putting a plaster on the affected area cures them immediately.

I was on a trial for an acne treatment once where you were zapped with a laser. Some people in the trial were zapped like the rest of us but the laser wasn't actually doing anything.

For any experiment to be credible you really need a control and placebo drugs offer this.

So lets take the acne trial I was on..... 40 people on the trial, it's possible that some people's skin may have improved without any treatment during the trial period. So you might split the group 50/50 and measure the number of spots on their faces every week for a month. If the control/placebo group show no significant improvement but the "live" group have less spots by the end of it, it would be pretty fair to say that the treatment successfully reduced the symtoms.
 
watch the derrin brown program on placebos. it was pretty interesting in that he (well, this front company) gave one guy a "pill" that was supposed to cure vertigo. it was in fact a sugar pill yet it cured him.
 
Thanks all - I guess that makes sense :).
 
Useful in real medicinal tests, or a means for unscrupulous people (Homeopathists are the worst) to take money off gullible people.
 
That's about it. In a blind test, the subjects don't know if they are receiving the drug or a placebo. Some research is also carried out using double blind testing where the people who are actually working with the subjects don't know either, to eliminate the possibility of bias during the evaluation phase, or inadvertent disclosure.

There can be a third group of subjects who don't recieve anything at all, for comparative purposes.
 
Something I have always wondered. If a 'placebo' actually works, was the person really in need of medication in the first place?
 
I bought a placebo to stick in the garden to keep the sun off me John, I`m gonna have to take it back to Homebase for a refund :(
 
Ben Goldacre's book Bad Science covers the placebo effect and how important and real it is and also pulls no punches attacking homeopathy and "nutritionists".
 
RichardtheSane said:
Something I have always wondered. If a 'placebo' actually works, was the person really in need of medication in the first place?
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It depends what you mean by "works". Placebos don't actually make people better; they make them FEEL like they're better (it's actually a bit more complicated, but this will do for our purposes).
This isn't a big problem when the condition will get better on its own anyway. With a cold or a mild allergy, for example, there's little difference between subjectively FEELING better and objectively BEING better, right? Analysis might discover you're still carrying just the same load of cold virus, but if you FEEL better, who cares?
And we all have our little placebos for self-limiting conditions like these. A cup of tea, chicken soup, a vit C drink, whatever - none of which really do anything.

The problem arises when you start trying placebos to treat problems that DO NOT get better on their own.
To give an extreme example: with cancer there is a VERY important difference between feeling better and being better. And it might be very dangerous to feel better if you've not also got someone checking if you actually are improving objectively.
 
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My understanding is that in drug trials, placebos are no longer used in most cases. A new drug has to be tested against an exiting one to see if it performs better (happy to be corrected).

+lots on the Goldacer book; fascinating - and frightening!
 
The placebo affect can even be affected by the colour of the pills given!

Jon - that is correct, as long as there is a current method that has shown to be effective, the new drug will be compared to the current drug rather than a placebo.

http://www.nhs.uk/Conditions/Clinical-trials/Pages/Fairtests.aspx

Comparing a treatment with a standard treatment

Where a treatment is already known to be effective from previous research, it is usually not considered right (ethical) to compare the new treatment with a placebo. The new treatment usually needs to be compared with a standard treatment that is already known to be helpful.
This makes it possible to determine whether the new treatment works better than the treatment already being used. New treatments are as likely to be worse as they are to be better than existing treatments.
 
jon ryan said:
My understanding is that in drug trials, placebos are no longer used in most cases. A new drug has to be tested against an exiting one to see if it performs better (happy to be corrected).

+lots on the Goldacer book; fascinating - and frightening!
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Almost right; they are still used in phase 2 trials- the testing against an existing drug is mainly in phase 3. (Also happy to be corrected as have only just started to be involved in clinical trials!)
 
PMK said:
This. A great read.

Gillian McKeith does not come off lightly.
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Thats probably the funniest chapter of the entire book, like how Ben Goldacre managed to buy a PhD in the name of his dead cat at the same place where Gillian McKeith 'earned' her non-accredited PhD.

I recently completed a Pharmacology degree, and on the first day of the course, the program leader spoke to us about what we were going to be doing etc, but nearly the first thing that he said was that if we believed in the 'nonsense' of homeopathy, then we were 'advised and encouraged' to change to a different course! Throughout the 3 years this guy took near every opportunity he could to say why homeopathy, 'natural things being better' etc were wrong and nonsense. And he was entirely right if you look at the evidence.
 
The placebo effect is far more complicated than that.

DorsetDude said:
Ben Goldacre's book Bad Science covers the placebo effect and how important and real it is and also pulls no punches attacking homeopathy and "nutritionists".
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Love this book and think it should be mandatory reading in school and in medical school.

ghoti said:
It depends what you mean by "works". Placebos don't actually make people better; they make them FEEL like they're better
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As an example of the placebo effect, humans were given an immunosuppressing drug. At the same time, they were given a flavoured drink. Eventually, the researchers found that if they gave just the flavoured drink, the immune system would respond as if it had been given the drug. This is far more advanced that just "feeling better". I could essentially lop your cerebral cortex (everything that makes you more than just a vegetable) and it would still induce this response.

s162216 said:
Thats probably the funniest chapter of the entire book, like how Ben Goldacre managed to buy a PhD in the name of his dead cat at the same place where Gillian McKeith 'earned' her non-accredited PhD.Throughout the 3 years this guy took near every opportunity he could to say why homeopathy, 'natural things being better' etc were wrong and nonsense. And he was entirely right if you look at the evidence.
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Homeopathy and the like have their own issues. They pick and choose studies to back their findings, which is just bias. Scientifically, if you did 100 trials of a homeopathic treatment, through statistics alone, at least 5 would be in favour of homeopathy. Evidence based medicine looks at all 100 trials and would say it doesn't work. Homeopathists would look at the 5 trials and use that as their evidence.
 
omens said:
Homeopathy and the like have their own issues. They pick and choose studies to back their findings, which is just bias. Scientifically, if you did 100 trials of a homeopathic treatment, through statistics alone, at least 5 would be in favour of homeopathy. Evidence based medicine looks at all 100 trials and would say it doesn't work. Homeopathists would look at the 5 trials and use that as their evidence.
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And of those 5 trials they'll choose, nearly all of them can be pretty much guaranteed to be of low quality (e.g lacking a control group etc) based on the 'evidence' that regularly gets presented by homeopathists...
 
omens said:
The placebo effect is far more complicated than that.

Love this book and think it should be mandatory reading in school and in medical school.

As an example of the placebo effect, humans were given an immunosuppressing drug. At the same time, they were given a flavoured drink. Eventually, the researchers found that if they gave just the flavoured drink, the immune system would respond as if it had been given the drug. This is far more advanced that just "feeling better". I could essentially lop your cerebral cortex (everything that makes you more than just a vegetable) and it would still induce this response.
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You are over-egging the pudding somewhat.
Placebo responses can feature components of both "patient expectation" and Pavlovian behavioural conditioning. The study you speak of (which was quite small; around 50 participants if I recall correctly) demonstrated measurable, if small, behavioral conditioning to immunosuppresant drugs delivered in a flavoured drink. Such that after a period of conditioning with the drug - and only after a period of conditioning with the drug - there was a physiological response to the drink alone.
Funnily enough, there was no effect of patient expectation on immunosuppression - which supports the idea that expectation in the absense of conditioning does not affect physiological response - but we know that expectation affects subjective experience of the condition. Seeing that the conditioning component is absent in most common examples of placebo effect, the study, albeit interesting, does not support the idea that placebos in general objectively alter the course of a disease.

Also, the idea that you could lop off someone's cerebral cortex and still be able to behaviourally condition them is one I would treat with some scepticism. The cerebral cortex is, I believe, crucial to the conditioned reflex. At least in animals. I doubt anyone's had ethical approval to carry out the equivalent studies in humans.
 
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omens said:
Homeopathy and the like have their own issues. They pick and choose studies to back their findings, which is just bias. Scientifically, if you did 100 trials of a homeopathic treatment, through statistics alone, at least 5 would be in favour of homeopathy. Evidence based medicine looks at all 100 trials and would say it doesn't work. Homeopathists would look at the 5 trials and use that as their evidence.
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Well, kinda. You've misunderstood the statistics a little bit.
You're using the conventional p-value of 0.05. But remember, this threshold is arbitrary. It doesn't reflect some universal truth that if you do 100 studies, five would always come out in support of an objectively wrong hypothesis. It's just that the probability of a result being less than 0.05 is the arbitrary benchmark for significance in many fields.
Many fields use other p thresholds. Medical trials often use p<0.01 for example.
 
ghoti said:
You are over-egging the pudding somewhat.
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What I was trying to point out was that the placebo effect is more than just the "patient expectation" and that it doesn't have to involve "patient expectation" at all.

ghoti said:
Also, the idea that you could lop off someone's cerebral cortex and still be able to behaviourally condition them is one I would treat with some scepticism. The cerebral cortex is, I believe, crucial to the conditioned reflex.
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Doesn't this mean that the higher functions of the brain were required? How would they then dampen down the immune response? My own conclusion from what I recall was that it didn't require the higher functions of the brain and hence you should be able to remove the cerebral cortex and still maintain the response.

ghoti said:
Well, kinda. You've misunderstood the statistics a little bit.
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Not really. I deliberately used the p<0.05 target as an example of how you can still have positive results. It was an oversimplification to drive home the point of how statistics are twisted by homeopaths to suit their agenda.
 
PLACEBO IS GREAT WITH A BIT OF BOLAN AND BOWIE MIXED IN:

[YOUTUBE]iuNdWqqk7m8[/YOUTUBE]
 
omens said:
What I was trying to point out was that the placebo effect is more than just the "patient expectation" and that it doesn't have to involve "patient expectation" at all.

Doesn't this mean that the higher functions of the brain were required? How would they then dampen down the immune response? My own conclusion from what I recall was that it didn't require the higher functions of the brain and hence you should be able to remove the cerebral cortex and still maintain the response.
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Nobody understands exactly how behavioural conditioning works in neurological terms, but higher functions & cerebral cortex are crucial to the phenomenon in animals so it's very likely that they are involved in humans too. It's very unlikely, in my opinion, that the cerebral cortex is sufficient for the observed immunosuppressant effect but highly likely that it is necessary. It may be to do with the component of the phenomenon which involves recognition of the novel stimulus. Who knows?
The original study to which you refer doesn't cover the effect's neurological basis.

And yes, you can have a conditioned physiological placebo response but my point is that this does not mean that all placebos have objective physiological effects because, in the huge majority of cases, the period of thorough behavioural conditioning with an efficacious drug is absent.

Regarding statistical significance; fair enough. It is very important to remember, however, that p values are arbitrary.
 
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DorsetDude said:
My brain urtz
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Just keep taking the tablets Keith. If they work, they could still be either real or placebos but as long as the head hurt's gone, who cares?
 
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