The Placebo Effect

[Ziggurat]

Next article is up:

The idea that four placebo pills are more powerful than two sounds magical – because it isn’t true

Make sure you go to the article, because there are links.

It wasn't actually that long ago that somebody proved stomach ulcers were caused by bacteria. But it was still long enough ago that everyone should know that. If I were on the IRB for any placebo studies of stomach ulcer treatments, I wouldn't allow them to proceed. Even if placebo treatment was better than no treatment, letting patients suffer from completely treatable conditions in order to study sub-optimal treatments seems highly unethical to me.

 

[Pixel42]

My understanding is that, once an effective treatment for a condition is known, new treatments which are hoped will be even more effective are compared to that rather than placebo. So the control group gets the existing treatment, whose effectiveness compared to placebo has already been established.

 

[Ziggurat]

My understanding is that, once an effective treatment for a condition is known, new treatments which are hoped will be even more effective are compared to that rather than placebo. So the control group gets the existing treatment, whose effectiveness compared to placebo has already been established.

Looking at the article, it seems like a lot of the placebo studies were actually quite old, dating back to the 70s, and a lot of the newer papers were just meta studies using that old data.

Given what we now know about replication crisis, using data that old which cannot even ethically be retested seems rather dubious. I wouldn’t trust any of it.

 

[arthwollipot]

Looking at the article, it seems like a lot of the placebo studies were actually quite old, dating back to the 70s, and a lot of the newer papers were just meta studies using that old data.

Given what we now know about replication crisis, using data that old which cannot even ethically be retested seems rather dubious. I wouldn’t trust any of it.

Yes, most of the data supporting a "powerful placebo" effect is old, but that just means that it has had longer to seep into the public consciousness. That's common with the public understanding of science - it usually lags well behind the cutting edge. Most people who are anti-nuclear energy are unaware of 4th generation fast breeder reactors, for example.

The powerful placebo effect demonstrates the same trend as other studies of pseudoscience, like homeopathy and psychic ability. The tighter the controls, the smaller the effect.

 

[jonesdave116]

Just reading this thread made me feel better! It's a miracle!

 

[arthwollipot]

I swear, I didn't contact him. He found us all on his own.

 

[Chanakya]

Okay, there was this view presented in this thread, that the placebo isn't really the "I think I'm getting better, therefore I do get better" that I'd believed to be, but merely a catch-all for all effects not attributed to individual causes and/or controlled for. And, given that people here tend in general to know that they're talking about, I accepted that as true.

In connection with something entirely unrelated to this thread (or indeed this forum), I'd just now been googling around a bit about the placebo effect, and it seems the overwhelming majority of references that come up do state that, to quote one random but representative sample, "the placebo effect is triggered by the person's belief in the benefit from the treatment and their expectation of feeling better".

So, what the hell is the placebo effect? Is there a psychological/psychosomatic element in play here or not?

Do people here who're saying there's no psychological mumbo jumbo involved, have any evidence to back up that claim? (Now I realize that's reversing the burden of proof thing, but, I mean to say, just plug "placebo", or "placebo effect" into your search engine, and see what comes up. Practically every hit will tell you about this psychosomatic angle. So is everyone out there wrong, and just we here right? A pinch of salt, that is to say, a pinch of evidence, might be called for here, no matter which way the burden of proof actually points.)

 

[Thermal]

Possibilities:

-patient's perception of symptoms altered by belief in treatment.
-patent was improving anyway and would have felt better with no placebo pill
-patient's belief in treatment kicked in body's natural endorphins or whatever
-placebo was in fact morphine and patient got hella high

 

[Chanakya]

Possibilities:

-patient's perception of symptoms altered by belief in treatment.
-patent was improving anyway and would have felt better with no placebo pill
-patient's belief in treatment kicked in body's natural endorphins or whatever-placebo was in fact morphine and patient got hella high

Does stuff like the highlighted actually happen?

I'd originally assumed it does. (Casually enough, and without giving it any thought.) It was brought up in this thread that it doesn't, and that placebo is merely a catchall term for all uncontrolled variables. And I saw no reason to doubt what was said here, and updated my views on this.

But now I find, on looking this up cursorily (in context of a discussion IRL) that most references that pop up do bring up the psychosomatic angle, the psychology thing ... the sort of thing you'd brought up here, and that I've highlighted above.

So that, I was wondering, what the case actually is.

 

[Thermal]

Does stuff like the highlighted actually happen?

I'd originally assumed it does. (Casually enough, and without giving it any thought.) It was brought up in this thread that it doesn't, and that placebo is merely a catchall term for all uncontrolled variables. And I saw no reason to doubt what was said here, and updated my views on this.

But now I find, on looking this up cursorily (in context of a discussion IRL) that most references that pop up do bring up the psychosomatic angle, the psychology thing ... the sort of thing you'd brought up here, and that I've highlighted above.

So that, I was wondering, what the case actually is.

Anecdotally, I'm quite positive you can will yourself to feeling better on the short term, sometimes for very physical damage that I can only attribute to a very real painkiller flowing in my veins. The hitch is very short term, IME.

 

[steenkh]

So, what the hell is the placebo effect? Is there a psychological/psychosomatic element in play here or not?

Placebo is the inert treatment used in a study to contrast with an active treatment. The placebo effect is whatever effect appears in contrast to not getting a treatment at all. Any mechanism is possible.

Bias, psychosomatics, statistics, treatments ignored in the study. All is possible.

 

[Chanakya]

Placebo is the inert treatment used in a study to contrast with an active treatment. The placebo effect is whatever effect appears in contrast to not getting a treatment at all. Any mechanism is possible.

Bias, psychosomatics, statistics, treatments ignored in the study. All is possible.

That highlighted is the key part I was asking about. Is it a thing at all? Because if it is, then it brings up right back to where we started from (as far as this aspect of the discussion).

To be fully clear: If there's a psychosomatic element at play, with placebos, then absolutely, there's an argument to be made for actively and deliberately capturing that effect, using whatever means, including for instance homeopathy. That that doesn't actually happen, was a large part of what this thread was about.

It would be nice to be able to arrive at some kind of conclusion that is, well, conclusive, and evidenced, as far as whether or not psychosomatic effects form any (significant) part of the placebo effect.

 

[Ziggurat]

That highlighted is the key part I was asking about. Is it a thing at all?

Probably. The weak placebo effect (meaning you feel better, not that you actually are better) does appear to be real. The strong placebo effect (meaning it can actually help you get better) does not appear to be real.

To be fully clear: If there's a psychosomatic element at play, with placebos, then absolutely, there's an argument to be made for actively and deliberately capturing that effect, using whatever means, including for instance homeopathy. That that doesn't actually happen, was a large part of what this thread was about.

A weak placebo may be worth exploiting by some means, but definitely not by any means. In particular, promoting homeopathy may have negative consequences that outweigh any benefits.

 

[arthwollipot]

A weak placebo may be worth exploiting by some means, but definitely not by any means. In particular, promoting homeopathy may have negative consequences that outweigh any benefits.

The main risk of relying on the weak placebo effect of, eg., homeopathy is that people will rely on that and neglect getting real medical aid.

 

[Chanakya]

Probably. The weak placebo effect (meaning you feel better, not that you actually are better) does appear to be real. The strong placebo effect (meaning it can actually help you get better) does not appear to be real.

Thanks for the clarification.

A weak placebo may be worth exploiting by some means, but definitely not by any means. In particular, promoting homeopathy may have negative consequences that outweigh any benefits.

The main risk of relying on the weak placebo effect of, eg., homeopathy is that people will rely on that and neglect getting real medical aid.

Sure, agreed.

But still, in as much this weak placebo's a thing, it's easy to imagine lots of ways to deliberately channel it. There's a great deal of medication that's designed to have people feel better, or feel less bad. That would represent a huge potential for deliberately using placebos, surely, whether (in some case) in place of medication, or whether along with medication. My impression --- admittedly uninformed impression, and I could be mistaken --- that this isn't really done, or at least done much.

 

[Ziggurat]

But still, in as much this weak placebo's a thing, it's easy to imagine lots of ways to deliberately channel it. There's a great deal of medication that's designed to have people feel better, or feel less bad. That would represent a huge potential for deliberately using placebos, surely, whether (in some case) in place of medication, or whether along with medication. My impression --- admittedly uninformed impression, and I could be mistaken --- that this isn't really done, or at least done much.

I suspect it's done quite a lot, just not talked about much because nobody wants to hear they got a placebo instead of real treatment. A patient comes to see a doctor with some minor problem, the doctor prescribes something, the patient leaves satisfied regardless of whether the medication actually does anything for their problem. And that's frequently OK, since many ailments resolve on their own anyways.

 

[Prometheus]

This thread brings back a vague memory I have of a discussion when I first joined the JREF forum. I'll have to see if I can find it...

 

[arthwollipot]

New paper in the Medical Journal of Australia (MJA):

Placebos in clinical care: a suggestion beyond the evidence

Christopher G Maher, Adrian C Traeger, Christina Abdel Shaheed and Mary O'Keeffe
Med J Aust 2021; 215 (6): 252-253.e1. || doi: 10.5694/mja2.51230
Published online: 20 September 2021

The recent enthusiasm for the clinical use of placebos seems driven by myths and misunderstandings

In the past few years, major medical journals have published commentaries considering whether placebos may have a role in clinical care. Some commentators seem to have concluded that placebos should be part of clinical care and have provided advice on implementation: “Clinician education, training manuals, and workshops might help with initial implementation”.1

The clinical use of placebos is often justified by pointing to their important treatment effects. Proponents have also argued that the placebo effect can be amplified by manipulating the physical appearance of the pill,2 that placebo effects vary across geographic regions,3 and that placebos are getting more effective over time.4,5 It has even been suggested that subterfuge is unnecessary; placebos can be honestly described as inert and still yield important clinical effects.1,6 Given the recent advocacy for the clinical use of placebos, it is timely to consider the evidence underpinning these claims.

...

Conclusion

Placebos remain important for clinical trials because they help achieve blinding and, thus, control of bias; however, there is no evidence that placebos have much to offer for clinical care. When administered in a blinded fashion, a placebo will provide a small effect, but the real treatment will normally provide better outcomes for the patient. A placebo supporter could counter that they could get a bigger placebo treatment effect by dispensing large, red, unusually shaped placebo pills, but they would be basing this on uncertain evidence. It may be better to dismiss placebos and instead manage patients with evidence‐based treatments.

 

[arthwollipot]

Here's the asthma article:

Placebo inhalers can’t treat asthma: another ‘powerful placebo’ myth busted

...The study found that patients using the real salbutamol inhaler reported a 50% improvement from baseline, and patients receiving no treatment arm reported just a 21% improvement. Astonishingly, patients using the fake inhaler reported a massive 45% improvement from baseline, almost as large as salbutamol.

A startling result, I’m sure you’d agree. A fake inhaler, with no medicine in it, improved asthma symptoms almost as much as salbutamol. In fact, there was no statistically significant difference between salbutamol, the fake inhaler, and the sham acupuncture. A powerful placebo indeed, and let’s be honest, this is bad news for salbutamol, which according to these data is no better than placebo.

But that’s just the data gathered when the patients were asked how they thought they were doing. The study did not rely solely on that measure but also recorded an objective measure of lung function: Forced Expiratory Volume (FEV) or, how hard you can blow into a tube.

The FEV data tell quite a different story from the patient self-reports. Again, patients using salbutamol had an objectively measurable 20% improvement in lung function, as measured by FEV. Patients getting no treatment had much smaller 7.1% improvement. However, using this objective measure, the placebo inhaler showed only a 7.5% improvement and the sham acupuncture only a 7.3% improvement, neither of which is statistically different to no treatment...

...They aren’t lying, certainly not maliciously. They genuinely believe that they are or will be doing better, even though we know from their lung function tests that they haven’t improved any more than if we had done nothing. There is no magic here, no demonstration of the amazing power of the mind over the body. Just psychology and statistics.

To the extent that we observe real objective clinical effects, they don’t look to be related to the placebo. To the extent we receive subjective clinical reports of placebo effects, they look very much like biased reporting.

 

[steenkh]

Here's the asthma article:

Placebo inhalers can’t treat asthma: another ‘powerful placebo’ myth busted

This is again a confirmation that you can’t treat illnesses with placebo, but you can treat patients’ perception of the illnesses.

 

[arthwollipot]

This is again a confirmation that you can’t treat illnesses with placebo, but you can treat patients’ perception of the illnesses.

Indeed, and this is what I've been saying all along. The problem is that if you're treating their perception of the illness, it might result in them not seeking necessary treatment because they feel that they don't need it. Far better to treat their perception of their illness by actually treating their illness.

This asthma study is a cornerstone of the "powerful placebo doesn't exist" argument, but it is far from being the only one. It looks like the articles are coming at a rate of about once a month, so I will continue to keep the forum informed

 

[arthwollipot]

By the way, though Mike has found this thread (he's a web designer and obviously noticed the link in website analytics) and registered at the forum, he appears disinclined to respond directly. For my money that's completely okay. I can do it adequately enough.

One of the things he mentioned to me in our exchange on Twitter (and as they were DMs I will not quote directly) is that he was a bit surprised that people were bringing up Ted Kaptchuk in defence of the effect of the placebo. Kaptchuk is an acupuncturist with a degree in Traditional Chinese Medicine. Despite being at Harvard Medical School he has no medical degree. He has been called out on Science Based Medicine several times for overselling his research. And Kathryn Hall, the person who was bigging up the research on Adam Ruins Everthing is his employee.

 

[arthwollipot]

Rebecca has weighed in - mostly in support of Dr Maher's paper.

https://skepchick.org/2021/12/why-the-placebo-effect-isnt-as-magical-as-you-think/

 

[arthwollipot]

We've had a bit of a wait, but the next article on the so-called "powerful placebo" is in:

Rather less than more: More or Less misses the mark on placebo effects

More or Less is an award-winning investigative radio show and podcast from the BBC. Presented by Tim Harford, the programme examines the accuracy of statistics in the news and popular culture. Their work is frequently praised by skeptics for its diligent deconstruction and debunking of misinformation. All of which made it more disappointing when, for their January 26th 2022 episode, More or Less seemed to get it so wrong in a brief conversation about the Placebo Effect.

The Powerless Placebo

The segment opened with a guest recounting the story of Henry Beecher, a US Army doctor who, we are told, ran into a shortage of morphine while working as a surgeon during World War Two. Forced to administer inert salt water injections instead, his patients nevertheless experienced – says More or Less – ‘an astonishing amount of pain relief.’

Unfortunately, there is little evidence this story is true. When the journalist Shannon Harvey set out to verify the tale, she was unable to find it anywhere in the corpus of Beecher’s published work, or in his personal archive held by Harvard. Rather the story appears to be a corruption of a case study where Beecher administered a sedative to a wounded man instead of a painkiller, reasoning his anxiety was contributing more to the pain than the wound itself. There was no morphine shortage, or inert injections.

That aside, Beecher is responsible for probably the single most influential paper in placebo effect research. Published by JAMA in 1955, The Powerful Placebo cites ‘fifteen illustrative studies’ involving 1,082 patients, which found that placebos have an average significant effectiveness of 35.2 ±2.2%, ‘a degree not widely recognised.’

In 1997, the Journal of Clinical Epidemiology published a modern re-analysis of Beecher’s fifteen papers. The authors, Kienle and Kiene, identify a raft of things which could give a false impression of a placebo effect...

This article also covers the claim that the placebo effect has been getting more powerful over time (it hasn't - we're just better now at controlling for previously uncontrolled factors), and it covers the 2007 hotel-cleaner study in which cleaners who were told that the work they did counts as exercise lost weight and had better blood pressure (there were lots of poorly controlled effects and a later replication failed to reproduce the results).

 

[Lukraak_Sisser]

From the Mitchell and Webb 'homeopathic medicine' sketch

"Sure, you can't save anyone with a true disease, but whenever someone comes in with a vague unease, a touch of the nerves or just more money than sense, you'll be there with what is basically water."

 

[arthwollipot]

David Mitchell appears to be a skeptic. He's had some epic rants on QI.

 

[Mojo]

By the way, though Mike has found this thread (he's a web designer and obviously noticed the link in website analytics) and registered at the forum, he appears disinclined to respond directly. For my money that's completely okay. I can do it adequately enough.

One of the things he mentioned to me in our exchange on Twitter (and as they were DMs I will not quote directly) is that he was a bit surprised that people were bringing up Ted Kaptchuk in defence of the effect of the placebo. Kaptchuk is an acupuncturist with a degree in Traditional Chinese Medicine. Despite being at Harvard Medical School he has no medical degree. He has been called out on Science Based Medicine several times for overselling his research. And Kathryn Hall, the person who was bigging up the research on Adam Ruins Everthing is his employee.

Here’s report of a recent paper that might be relevant here: https://www.theguardian.com/science...eactions-not-caused-by-vaccine-study-suggests

 

[Ziggurat]

From the Mitchell and Webb 'homeopathic medicine' sketch

"Sure, you can't save anyone with a true disease, but whenever someone comes in with a vague unease, a touch of the nerves or just more money than sense, you'll be there with what is basically water."

I also liked their nutritionist sketch.

 

[arthwollipot]

Here’s report of a recent paper that might be relevant here: https://www.theguardian.com/science...eactions-not-caused-by-vaccine-study-suggests

I believe Mike has spoken about the nocebo effect, but I don't recall specifically what he has said. As I understand it though, nocebo effects are a vastly different thing from the purported Powerful Placebo effect.

 

[arthwollipot]

This is worth reading in full, because it is a comprehensive summary of the issues with the so-called placebo effect.

More wishful thinking than medical reality: “Placebos” by Kathryn T. Hall

From the conclusion:

Much has changed in medical science since the 18th century and even again since the 1950s – but what hasn’t changed is the need for things like the placebo effect which offer the necessary comparison to determine an effective novel treatment or at least rule out something that doesn’t work. The latter is whether the placebo is most effective: if acupuncture does no better than placebo it means that acupuncture is not an effective intervention in that study – not that placebo is as effective.

Hall’s book is exactly this. It is illustrative in its portrayal of the placebo effect for how the public hears it. However, they only hear it that way because of books like this and shoddy reporting on medical science in the English-speaking world. Hall is trying to claim that there is something extra-normal going on; that belief somehow shapes reality, but reality always wins. The placebo effect cannot make anyone better, just as Hall does not make the case here.

 

[steenkh]

Interesting indeed. But I was also shocked to read the quote where dr. Hall says: “The key finding was not that these strange and bewildering remedies didn’t work; it was that the sham devices worked just as well as the real ones.” I thought that everybody with a medical education would know that it means that the sham treatment did not work at all.

It casts a different light on a phrase commonly used by doctors: “There is no documentation that this treatment works”. I always thought that it was a careful phrasing of “this treatment does not work”, but if more doctors are like dr. Hall, it could mean “the treatment works, but we still haven’t got the documentation”.

 

[arthwollipot]

Indeed. If the placebo works just as well as the intervention, that doesn't indicate that the placebo works, it indicates that the intervention does not.

 

[arthwollipot]

Here we go. This is a long video (42:11), but in it, Mike Hall outlines the main evidence for the so-called "powerful placebo" effect being a myth. Enjoy.

 

[dann]

Great lecture, but the text is bloody awful:

The placebo effect is one of the most powerful medical responses there is. It can cure your knee pain, relieve your asthma, or even help you lose weight. This isn't wishy-washy alternative New Age nonsense, it works in animals, it works in children, and it even works when you think it won't. So why, asks Mike Hall, does the best evidence tell us that none of this is true? Why does the data show that placebos perform no better than doing nothing? And how is this myth so deeply ingrained and unquestioned in modern medicine?

No, it's not a powerful medical response, it doesn't cure your damaged knee, it does nothing for your asthma, and it doesn't make you lose weight. Claiming that it does is actually alternative New Age nonsense. And it also doesn't work in animals or children.
It should have started with: "We are told that ..."
The second half of the paragraph is great, and the lecture itself makes it clear that placebo may have a powerful psychological effect - in both patients and doctors - but no real physiological effect.

 

[dann]

Interesting indeed. But I was also shocked to read the quote where dr. Hall says: “The key finding was not that these strange and bewildering remedies didn’t work; it was that the sham devices worked just as well as the real ones.” I thought that everybody with a medical education would know that it means that the sham treatment did not work at all.

Indeed. If the placebo works just as well as the intervention, that doesn't indicate that the placebo works, it indicates that the intervention does not.

This is made very clear in the QED video.

 

[dann]

I believe Mike has spoken about the nocebo effect, but I don't recall specifically what he has said. As I understand it though, nocebo effects are a vastly different thing from the purported Powerful Placebo effect.

You can see the impact of the nocebo effect on the 'Havana syndrome' sufferers and other cases of patients being told by their doctors that they suffer from something much more serious than they actually do.
I can recommend neurologist Robert Baloh's book Medically Unexplained Symptoms: A Brain-Centered Approach (2021), which I'm currently reading.

 

[Roger Ramjets]

This is made very clear in the QED video.

Not so fast.

The first example in the QED video showed a placebo response almost as powerful as the real treatment. It only 'disappeared' when an objective measurement was made. If this isn't done then the study has failed to collect the necessary data. But getting truly objective data can be difficult.

It would be a pity if an effective treatment was discarded for being 'no better than placebo' when the real failure was the study itself. Where a strong placebo effect is found it should be investigated to find the cause(s). You should not merely presume that the treatment was ineffective.

 

[arthwollipot]

Not so fast.

The first example in the QED video showed a placebo response almost as powerful as the real treatment. It only 'disappeared' when an objective measurement was made. If this isn't done then the study has failed to collect the necessary data. But getting truly objective data can be difficult.

It would be a pity if an effective treatment was discarded for being 'no better than placebo' when the real failure was the study itself. Where a strong placebo effect is found it should be investigated to find the cause(s). You should not merely presume that the treatment was ineffective.

Right, but the placebo effect disappeared in those cases where there was an objective measure of efficacy - for example, in the asthma study. The difference between what people self-reported and what was actually measured was clear.

"Yes, I felt that I could breathe more easily" when actual measurement of lung capacity was unchanged. That sort of thing. That's where the Placebo Effect disappears.

I was actually a little disappointed that Mike didn't mention Ted Kaptchuk and the Harvard school of "placebo studies", since that's the source of a lot of incorrect information about the so-called "powerful placebo effect".

 

[steenkh]

"Yes, I felt that I could breathe more easily" when actual measurement of lung capacity was unchanged. That sort of thing. That's where the Placebo Effect disappears.

I always thought that “Yes, I felt that I could breathe more easily" was the placebo effect, and that of course the lung capacity was unchanged, or worsened.

 

[arthwollipot]

I always thought that “Yes, I felt that I could breathe more easily" was the placebo effect, and that of course the lung capacity was unchanged, or worsened.

Yes, and it can be explained by a number of things, like (for example) the person knowing that they are part of a trial and feeling obligated to report a positive result.