Placebo Effect Question

[Antranik1]

Hi everybody,

In regards to the placebo effect, I'm curious to know how often the response occurs. Do we have a lot of documented information on how often the placebo effect occurs for every condition? I'm guessing that for one illness it may be 30%, for another it may be 35%.. are there illnesses where the placebo effect could be really low, like less than 5%, like for cancer? I'm guessing we have a ton of information in regards to this since all the pharmaceutical drug testing is placebo-controlled. Which also makes me wonder how much stronger does a drug have to be than a placebo to be determined effective? If 50% of depressed people aren't depressed anymore after 3 months, and 55% of depressed people aren't depressed anymore after 3 months of taking drug XYZ, is that enough to prove it is effective? Anyway, it's just a topic that really intrigues me, any interesting facts or tidbits would be appreciated. Thanks.

[drkitten]

In regards to the placebo effect, I'm curious to know how often the response occurs.

Depends on the condition. The "placebo effect" for drugs that cure headaches is near 100%, since headaches will eventually go away on their own. The "placebo effect" for drugs that regenerate missing arms is close to zero.

Do we have a lot of documented information on how often the placebo effect occurs for every condition?

No, that would neither be practical to get, nor would it be useful, because so much of the "placebo effect" is situation-dependent.

Which also makes me wonder how much stronger does a drug have to be than a placebo to be determined effective?

There is no fixed limit, since it depends on how many people were in the study.

Actually, very few clinical studies are "placebo controlled" any more. It's medically inethical to withhold treatment, so usually the control group will be treated with a standard real drug instead of a placebo. After all, the point isn't just to find new drugs, but to find new drugs that are an improvement on what we currently have.

[tkingdoll]

Actually, very few clinical studies are "placebo controlled" any more. It's medically inethical to withhold treatment, so usually the control group will be treated with a standard real drug instead of a placebo. After all, the point isn't just to find new drugs, but to find new drugs that are an improvement on what we currently have.

In the case of witholding treatment from people with medical conditions, it's absolutely unethical. Of course, this only applies if there are existing treatments for the condition. If there are not, then you are potentially testing nothing against nothing which is not unethical.

Which reminds me of a recent Bad Science article in which Ben discusses a large trial of fish oil pills among schoolkids to see if it improved brainpower, concentration, and well, anything. There was no placebo control group, one of the objections being that it was unethical to deprive some kids of the benefit of the fish oil supplements :boggled:

http://www.guardian.co.uk/science/2007/sep/22/1

Anyway, I raise this point because the publicity surrounding a trial will have a placebo effect, not something the OP takes into account.

ETA: the most recent Bad Science article discuss the placebo effect some more, with a nice little description:

http://www.guardian.co.uk/science/2007/sep/29/acupuncture

Now as I have said so many times before, the placebo effect is not about a sugar pill, it's about the cultural meaning of a treatment, and our expectations: we know from research that two sugar pills are more effective than one, that a salt water injection is better for pain than a sugar pill, that colour and packaging have a beneficial effect, and so on.

Interestingly, there has even been a trial on patients with arm pain specifically comparing a placebo pill against a placebo ritual involving a sham medical device, modelled on acupuncture, which found that the elaborate ritual was more effective than the simple sugar pill. "Placebo" is not a unitary phenomenon; there is not "one type of placebo".

[fls]

Hi everybody,

In regards to the placebo effect, I'm curious to know how often the response occurs. Do we have a lot of documented information on how often the placebo effect occurs for every condition? I'm guessing that for one illness it may be 30%, for another it may be 35%.. are there illnesses where the placebo effect could be really low, like less than 5%, like for cancer? I'm guessing we have a ton of information in regards to this since all the pharmaceutical drug testing is placebo-controlled. Which also makes me wonder how much stronger does a drug have to be than a placebo to be determined effective? If 50% of depressed people aren't depressed anymore after 3 months, and 55% of depressed people aren't depressed anymore after 3 months of taking drug XYZ, is that enough to prove it is effective? Anyway, it's just a topic that really intrigues me, any interesting facts or tidbits would be appreciated. Thanks.

It helps to sort this out if you start by realizing that there is no placebo effect (i.e. an effect specific to the taking of a placebo). The placebo group in a research study gives us information about the normal course of events - people get better, worse, or stay the same; symptoms wax and wane; they pick up new diseases; etc. And it gives us information about what kinds of things influence our subjective perceptions, both as a patient describing the amount of pain they are experiencing and as a researcher interpreting an x-ray.

So when we talk about the placebo effect, we are simply giving a description of what happened to the people in the placebo group. If 35% of the people got better, it's just a measure of how many people were going to get better anyway. Can these numbers be generalized to all people with the condition? No. People who participate in studies tend to come from a very selected population (they may differ in important ways from the average person with the disease). You can only really generalize samples of people to the population from which they are drawn, not the general population. At best, you could consider it a ballpark figure for the general population - like "not very many", "some", "most".

The difference between 50 and 55 percent can be demonstrated if your study is well-designed and you have enough people.

Linda

[Antranik1]

Actually, very few clinical studies are "placebo controlled" any more. It's medically inethical to withhold treatment, so usually the control group will be treated with a standard real drug instead of a placebo. After all, the point isn't just to find new drugs, but to find new drugs that are an improvement on what we currently have.

So there a time where it wasn't medically unethical to withhold treatment to test and find the standard drug? Or was it just that there was no treatment available so.. there was nothing unethical about it given the circumstances?

[fls]

Actually, very few clinical studies are "placebo controlled" any more. It's medically inethical to withhold treatment, so usually the control group will be treated with a standard real drug instead of a placebo. After all, the point isn't just to find new drugs, but to find new drugs that are an improvement on what we currently have.

Most clincial studies are placebo controlled (still). It's just a matter of whether or not the groups are also receiving a standard drug.

ETA: To clarify...I don't think that "placebo group" has to mean "untreated group". Clinical trials may be testing several different drugs against each other, a new drug compared to an old drug, or other combinations. But they still set it up so the patients don't know for sure which group they are in and which of the pills they are taking are active (i.e. they are still taking placebos).

Linda

[Antranik1]

Other than limbs regenerating... what else has a very low response to anything?

(And thanks for the clarification Linda)

[fls]

So there a time where it wasn't medically unethical to withhold treatment to test and find the standard drug? Or was it just that there was no treatment available so.. there was nothing unethical about it given the circumstances?

Ethical practice says that you give what can reasonably be assumed to be the best treatment. If you have no evidence otherwise, it may be reasonable to assume the best treatment may be no treatment.

Linda

[fls]

Other than limbs regenerating... what else has a very low response to anything?

Any disease with a very low 5 years survival rate. Some cancers - particularly in advanced stages. End-stage heart disease. Liver failure. Kidney failure.

Linda

[drkitten]

So there a time where it wasn't medically unethical to withhold treatment to test and find the standard drug?

Of course. Medical ethics is a relatively new discipline, and really only took off after the second World War. In the USA, as recently as 1933, it was not considered inethical to withhold treatment from syphillitics (http://www.brown.edu/Courses/Bio_160/Projects2000/Ethics/TUSKEGEESYPHILISSTUDY.html) in order to chart the progression of the disease (and the study continued into the 1970s).

[fls]

Of course. Medical ethics is a relatively new discipline, and really only took off after the second World War. In the USA, as recently as 1933, it was not considered inethical to withhold treatment from syphillitics (http://www.brown.edu/Courses/Bio_160/Projects2000/Ethics/TUSKEGEESYPHILISSTUDY.html) in order to chart the progression of the disease (and the study continued into the 1970s).

To be fair, it wasn't until 10 years after the study started that there was any effective treatment for syphillis anyway. And the study throughout was in clear violation of the medical ethics of the time (including 1933) - i.e. it was considered unethical to withhold treatment from syphillitics. It's simply that the researchers got away with it for a long time because the subjects were vulnerable. The real value from this egregious undertaking was that the procedure for undertaking medical research was formalized to ensure that individuals couldn't get away with unethical behaviour, rather than a change in the ethics. Although there have been changes in the details of the ethics as well.

Linda

[blutoski]

It helps to sort this out if you start by realizing that there is no placebo effect (i.e. an effect specific to the taking of a placebo). The placebo group in a research study gives us information about the normal course of events - people get better, worse, or stay the same; symptoms wax and wane; they pick up new diseases; etc. And it gives us information about what kinds of things influence our subjective perceptions, both as a patient describing the amount of pain they are experiencing and as a researcher interpreting an x-ray.

So when we talk about the placebo effect, we are simply giving a description of what happened to the people in the placebo group. If 35% of the people got better, it's just a measure of how many people were going to get better anyway. Can these numbers be generalized to all people with the condition? No. People who participate in studies tend to come from a very selected population (they may differ in important ways from the average person with the disease). You can only really generalize samples of people to the population from which they are drawn, not the general population. At best, you could consider it a ballpark figure for the general population - like "not very many", "some", "most".

The difference between 50 and 55 percent can be demonstrated if your study is well-designed and you have enough people.

Linda

I like to use the phrase "placebo group results" instead of "placebo effect," as the latter assumes something unproven: that placebo can produce an effect.

The only thing I'd like to add is that some experiments do add a third 'nontreatment' or 'standard treatment' group, against which the placebo group can be compared. This comparison is shaky, though, for a variety of reasons. eg: patients may have been on standard/nontreatment for quite a long time, and improvement is doubtful at this point, or the intention-to-treat approach may have a dropout artefact that exaggerates nontreatment failure to the benefit of placebo/experimental group results. I think this is what happened in the recent acupuncture study.

These multiple-cohort experiments are very informative, because the placebo group rarely does significantly better than nontreatment, and this gives us good insight into the true nature of the reported improvements.

[robinson]

Nature Medicine 7, 7 (2001)
doi:10.1038/83389
FDA uneasy about placebo revision
Tom Hollon

Although not legally binding, revisions to the Declaration of Helsinki regarding the use of placebos in clinical trials have created a stir in the United States Food and Drug Administration (FDA). A senior official has declared the changes wrong both in terms of ethics and science.

The Declaration, drafted by the World Medical Association, outlines ethical practices to be followed in medical experiments with humans. The revised section on placebo use states that all clinical trial patients should receive the best existing therapies and that placebos for control groups are acceptable only when no proven treatments exist (Nature Med. 6, 1198; 2000). This is anathema to the way clinical trials have been conducted for decades.

Although they are under no obligation to implement the current changes, the FDA is concerned about the revision because its regulations require trials conducted outside the US to be in accord with the Declaration's 1975 version. FDA is now pondering to what extent, if any, trial sponsors will be required to comply with the placebo revision.

Robert Temple, director of medical policy at the FDA's Center for Drug Evaluation and Research, vociferously disagrees with the new policy, calling its ethics "bizarre" and its consequences for medicine "a huge loss." In his view, discarding placebo use from clinical trials would effectively end the development of several categories of drugs.

The revised declaration requires non-inferiority trials, in which new drugs must be tested against and proven no worse than established drugs. These studies work for antibiotics and most cancer drugs because there is a clear and large difference between an effective drug and a placebo. But where drug effects are less pronounced, such as antihypertensive, antihistamine, hypnotic and mild analgesic medicines, "the study does not actually work unless it could have distinguished between an active drug and a placebo. And [with the revision] you wouldn't know whether it was capable of doing that because you don't have a placebo," explains Temple. This is why the FDA sometimes refuses to approve drugs for which placebo comparisons are absent.

[Kumar]

Depends on the condition. The "placebo effect" for drugs that cure headaches is near 100%, since headaches will eventually go away on their own. The "placebo effect" for drugs that regenerate missing arms is close to zero.



No, that would neither be practical to get, nor would it be useful, because so much of the "placebo effect" is situation-dependent.

Physical basis of placebo is currently researched, dopamine release in some brain part. It is due to reward expectation, motivation etc.



There is no fixed limit, since it depends on how many people were in the study.

Actually, very few clinical studies are "placebo controlled" any more. It's medically inethical to withhold treatment, so usually the control group will be treated with a standard real drug instead of a placebo. After all, the point isn't just to find new drugs, but to find new drugs that are an improvement on what we currently have.

If this is current practice, how can we be sure, what is doing what esp. in diseases which have longer or life longer impacts?

[fls]

Robert Temple, director of medical policy at the FDA's Center for Drug Evaluation and Research, vociferously disagrees with the new policy, calling its ethics "bizarre" and its consequences for medicine "a huge loss." In his view, discarding placebo use from clinical trials would effectively end the development of several categories of drugs.

The revised declaration requires non-inferiority trials, in which new drugs must be tested against and proven no worse than established drugs. These studies work for antibiotics and most cancer drugs because there is a clear and large difference between an effective drug and a placebo. But where drug effects are less pronounced, such as antihypertensive, antihistamine, hypnotic and mild analgesic medicines, "the study does not actually work unless it could have distinguished between an active drug and a placebo. And [with the revision] you wouldn't know whether it was capable of doing that because you don't have a placebo," explains Temple. This is why the FDA sometimes refuses to approve drugs for which placebo comparisons are absent.

Maybe "placebo group" does have to mean "untreated group".

The FDA is right to be critical of these requirements, as it shifts from trying to avoid Type I error to trying to avoid Type II error - a much more difficult endeavour. Because of the standard levels used for alpha (chance of a type I error) and beta (chance of a type II error), it is easier to 'prove' no difference than it is to 'prove' a difference.

This is an area that is hotly debated. It's relatively clear that if a proven treatment exists that prevents progression of disease or disability, it should be used instead of placebo. But what of short time periods where any progression would be miniscule? Or what of conditions where the treatment is of a symptom, such as pain or depressed mood? Does the benefit of acquiring knowledge outweigh the temporary reduction in patient care, given that it is not the patient who receives the benefit?

Linda

[drkitten]

If this is current practice, how can we be sure, what is doing what esp. in diseases which have longer or life longer impacts?

By doing the science properly. If the treatment group shows better results than the control group, then we know that something is doing something, and that's enough to get started on clinical use. As to explanations -- well, science can never "be sure" of ANYTHING. All we have is a really good guess that if I let go of this hammer, it will fall. But we're not sure of it.

[Unalienable]

A few years ago I had a common wart on my foot, I did a little research and found that it was the virus called papilloma, and that it's very common, not particularly harmful, and curable using a brute-force method of killing millions of skin cells, both healthy and infected, until you force it into remission.

But here's what made my jaw hit the floor... I was reading up on a variety of experimental cures for papilloma virus, and what I discovered is that in all of the experiments they would compare the effects of a salve (containing the experimental medicine) against a salve that contains only inert ingrediants. "Why don't they simply compare a wart treated with the salve, to a wart not treated whatsoever?" I thought to myself. The answer was simple: because even a salve containing inert ingrediants will kill the papilloma virus if the patient believes that the salve might help.

Now I can easily see why a headache medicine might show positive benefits even if it is inert. The person's mind might fool itself into relieving pain, because of the expectation of pain relief. But a virus, on one's foot? What 'state of mind' enables our feet to fight off a virus more effectively? It's positively mind-blowing.

[fls]

A few years ago I had a common wart on my foot, I did a little research and found that it was the virus called papilloma, and that it's very common, not particularly harmful, and curable using a brute-force method of killing millions of skin cells, both healthy and infected, until you force it into remission.

But here's what made my jaw hit the floor... I was reading up on a variety of experimental cures for papilloma virus, and what I discovered is that in all of the experiments they would compare the effects of a salve (containing the experimental medicine) against a salve that contains only inert ingrediants. "Why don't they simply compare a wart treated with the salve, to a wart not treated whatsoever?" I thought to myself. The answer was simple: because even a salve containing inert ingrediants will kill the papilloma virus if the patient believes that the salve might help.

Now I can easily see why a headache medicine might show positive benefits even if it is inert. The person's mind might fool itself into relieving pain, because of the expectation of pain relief. But a virus, on one's foot? What 'state of mind' enables our feet to fight off a virus more effectively? It's positively mind-blowing.

A large portion of warts go away without any treatment, just like headaches, regardless of your state of mind.

Linda

[genesplicer]

A few years ago I had a common wart on my foot, I did a little research and found that it was the virus called papilloma, and that it's very common, not particularly harmful, and curable using a brute-force method of killing millions of skin cells, both healthy and infected, until you force it into remission.

But here's what made my jaw hit the floor... I was reading up on a variety of experimental cures for papilloma virus, and what I discovered is that in all of the experiments they would compare the effects of a salve (containing the experimental medicine) against a salve that contains only inert ingrediants. "Why don't they simply compare a wart treated with the salve, to a wart not treated whatsoever?" I thought to myself. The answer was simple: because even a salve containing inert ingrediants will kill the papilloma virus if the patient believes that the salve might help.

Now I can easily see why a headache medicine might show positive benefits even if it is inert. The person's mind might fool itself into relieving pain, because of the expectation of pain relief. But a virus, on one's foot? What 'state of mind' enables our feet to fight off a virus more effectively? It's positively mind-blowing.

It could also be that a positive outlook boosts the immune system, which will help combat the virus...

[Kumar]

By doing the science properly. If the treatment group shows better results than the control group, then we know that something is doing something, and that's enough to get started on clinical use. As to explanations -- well, science can never "be sure" of ANYTHING. All we have is a really good guess that if I let go of this hammer, it will fall. But we're not sure of it.

That will be just experimenting stage by staking our body.

[Graham Jackman]

The other aspect of the placebo effect is in apparent side effects. If you conduct a clinical trial comparing an inactive treatment (placebo) against your test drug, it is advisable to monitor both groups for apparent side effects such as aches, nausea, fainting etc.. If you find no difference between the groups you are reasonably confident that the side-effects are due to normal occurrences or the imagined effect of treatment rather than truly drug-related. If homeopathy is thought to be unsuited to testing by double blind procedures, I wonder if they ever record such side-effects. of course it may be minimised by the practitioner implying that this treatment will do nothing but good, whereas in normal clinical practice we would ask the patient to report any side-effect, which may lead to more being reported.

[Kumar]

The Biochemical and Neuroendocrine Bases of the Hyperalgesic Nocebo Effect

. These data indicate a close relationship between anxiety and nocebo hyperalgesia, in which the CCKergic systems play a key role in anxiety-induced hyperalgesia. These results, together with previous findings showing that placebo analgesia is mediated by endogenous opioids, suggest that the analgesic placebo/hyperalgesic nocebo phenomenon may involve the opposite activation of endogenous opioidergic and CCKergic systems.
http://www.jneurosci.org/cgi/content/abstract/26/46/12014

The Biochemical Bases for Reward
Implications for the Placebo Effect
Raúl de la Fuentefernández
A. Jon Stoessl

Pacific Parkinson’s Research Centre, University of British Columbia

The authors propose that the placebo effect is mediated by reward-related mechanisms. Recent evidence suggests that it is the expectation of reward (in this case, the expectation of clinical benefit) that triggers the placebo response. In Parkinson’s disease, the placebo effect is mediated by the release of dopamine in the striatum. The authors argue that placebo-induced dopamine release in limbic structures, particularly in the nucleus accumbens, could also be a major biochemical substrate for the placebo effect encountered in other medical disorders. Other neuroactive substances involved in the reward circuitry (e.g., opioids) are also likely to contribute to the placebo response, and such contribution may be disorder specific (e.g., opioid release in placebo analgesia; serotonin regulation in response to placebo antidepressants). In addition, placebos may have a role in substitution programs for the treatment of drug addiction.
http://ehp.sagepub.com/cgi/content/abstract/25/4/387

Few people can be devited other benefited by above basis.

[Kumar]

The other aspect of the placebo effect is in apparent side effects. If you conduct a clinical trial comparing an inactive treatment (placebo) against your test drug, it is advisable to monitor both groups for apparent side effects such as aches, nausea, fainting etc.. If you find no difference between the groups you are reasonably confident that the side-effects are due to normal occurrences or the imagined effect of treatment rather than truly drug-related. If homeopathy is thought to be unsuited to testing by double blind procedures, I wonder if they ever record such side-effects. of course it may be minimised by the practitioner implying that this treatment will do nothing but good, whereas in normal clinical practice we would ask the patient to report any side-effect, which may lead to more being reported.

They note aggravations in right and wrong directiond, proving effects and improvements.

[Mashuna]

They note aggravations in right and wrong directiond, proving effects and improvements.

But they don't compare them against a control group, they just claim everything is caused by the treatment.

[Kumar]

But they don't compare them against a control group, they just claim everything is caused by the treatment. They do try but can get inconsistent outcomes dye to many factors specific to these, as I indicated previously. However, if few out of a group can get placebo others not, this itself shows variations.

[drkitten]

That will be just experimenting stage by staking our body.

Given that you can't even prove that you have a body or that other people exist, how do you expect to prove that any substance will have a beneficial effect on other people's bodies?

[Kumar]

Given that you can't even prove that you have a body or that other people exist, how do you expect to prove that any substance will have a beneficial effect on other people's bodies?

Energetic effects, prime force and/or secondary force/s based.

[fagin]

Energetic effects, prime force and/or secondary force/s based.

Primary force= Batman
Secondary force=Robin
??

[Unalienable]

A large portion of warts go away without any treatment, just like headaches, regardless of your state of mind.

That's absolutely true, but it's very well understood (if not proven) by people in this industry that a salve containing nothing will make a wart go away in a larger percentage of the population than warts untreated. So it's not just a matter of some salves being applied needlessly to a wart that was about to vanish anyhow. The "state of mind" obviously has some very real measurable impact in a way that, to my knowledge, science doesn't have a very deep understand of.

Incidentally, I also read about a procedure that dermatologists use on children. They take a red magic marker and make a spot on the wart and instruct the child to do the same thing every day. Of course, the chemicals in the marker are mostly harmless and inert, but the doctor is trying to kill the wart strictly through invoking a placebo reaction. Because children are so gullible by nature, they are likely to believe the "red magic marker" method, and therefore it works for them. Very few doctors would try this on an adult, because if the patient realizes it's a scam, the placebo effect vanishes.

It could also be that a positive outlook boosts the immune system, which will help combat the virus...

That's exactly what I mean. How "positive outlook" can translate into "more effective viral fighting agents in your foot cells" is the part that I am hazy about. In college I was friends with a guy who, for lack of a better word, let's call him a "mystic." He used to explain how he could fight off a cold or some other infection by going into a medidative state and imaginging a shark swimming through his blood, the shark a symbol of the most ferocious fighter, and this shark would kill the enemies of his blood. Yeah I know, it sounds like a bunch of "woo", but when you think about the wart-reaction there might be something to his mumbo jumbo. Positive thinking = effective immune system response.

[fls]

That's absolutely true, but it's very well understood (if not proven) by people in this industry that a salve containing nothing will make a wart go away in a larger percentage of the population than warts untreated. So it's not just a matter of some salves being applied needlessly to a wart that was about to vanish anyhow.

How would you know that?

You may or may not be aware that there are some biases (e.g. lead-time, selection, length time, regression to the mean) associated with collecting a group of people to study that make it more likely that you will see results - i.e. it's the bias in the way that we collect people to study that produces the results, not anything specific to the study including the taking of a placebo treatment. Some people have ignored this and tried to compare the results in the placebo treated group to what we see in everyday life. Yes, the placebo treated group often does better than what we'd expect. But it's not because they received placebo, but because they were placed in a group.

For example, prostate cancer roughly follows two different courses - a fairly indolent course that may be present for years without spread, or a more agressive course that progresses steadily and spreads throughout the body. If you go looking for prostate cancer, you are more likely to find the slow-growing kind, just because it is around for much longer. And if you collect men with prostate cancer for a study, it is likely that a higher portion of them will have the slow growing kind than would be found in the general population. So your study group, because it is biased towards collecting men who are going to do better anyway, is going to show a placebo group that does better than expected from the general population of men with prostate cancer. This is a length time bias. It doesn't mean that the placebo had some sort of mind-body effect though. If you actually compare groups given placebo vs. groups given nothing, there is no difference except on some subjective perceptions.

The "state of mind" obviously has some very real measurable impact in a way that, to my knowledge, science doesn't have a very deep understand of.

Can you give an example of some research where the impact from this state of mind has been measured?

Incidentally, I also read about a procedure that dermatologists use on children. They take a red magic marker and make a spot on the wart and instruct the child to do the same thing every day. Of course, the chemicals in the marker are mostly harmless and inert, but the doctor is trying to kill the wart strictly through invoking a placebo reaction. Because children are so gullible by nature, they are likely to believe the "red magic marker" method, and therefore it works for them. Very few doctors would try this on an adult, because if the patient realizes it's a scam, the placebo effect vanishes.

Do we really know what was going to happen? That the wart wasn't going to go away? All the marker ensures is that when the wart does go away, it will be noticed, instead of forgotten.

That's exactly what I mean. How "positive outlook" can translate into "more effective viral fighting agents in your foot cells" is the part that I am hazy about. In college I was friends with a guy who, for lack of a better word, let's call him a "mystic." He used to explain how he could fight off a cold or some other infection by going into a medidative state and imaginging a shark swimming through his blood, the shark a symbol of the most ferocious fighter, and this shark would kill the enemies of his blood. Yeah I know, it sounds like a bunch of "woo", but when you think about the wart-reaction there might be something to his mumbo jumbo. Positive thinking = effective immune system response.

Cuz his cold wouldn't have gone away otherwise?

There has been some interesting research on some measurable physiologic changes with placebo. And acute stress can have a small suppressive effect on the immune system (so methods of reducing stress can help remove this suppression). But it hasn't been shown to produce changes in disease outcomes. I'm not saying that we shouldn't continue to study this, or that something useful won't come out of it, but whether or not there is anything there has been way overblown by the woo crowd. And, if present, must be very small.

Linda

[Unalienable]

fls:

You asked "How would I know that "

My answer, although perhaps misguided, is that in all the studies involving topical creams that I examined the test was to compare an inert cream with one containing the medicine. If the placebo effect was impossible when it comes to viral-immune responses then the application of the placebo cream could be eliminated, and doctors should feel comfortable comparing their proposed medicine with untreated warts. However, it could be argued that this practice is just done out of convention rather than necessity, and furthermore you presented another interesting argument about bias of study groups.

What you said about the natural bias due to the timing of prostate cancer is very interesting, and I had never thought of that. It strikes me as particularly relevant because warts have a characteristic life cycle: they either quickly show up and vanish, or they stick around stubbornly resisting treatment and often start to multiply.

I'm going to skip your question regarding the red-marker anecdote just because I'm short on time and it's not particularly important; my point was just that the doctors behave as if the placebo-immune effect is real, but in any case, the methods that doctors ues to treat their patients doesn't prove anything.

Your most important question was [i]Can you give an example of some research where the impact from this state of mind has been measured? and my answer is "Not off hand but if I can locate it I will certainly share it." Your tone indicates to me that you are skeptical that any such legitimate research exists--and if you're right then what can I say, other than that I was wrong? However I boldly predict that I'll be able to come back with something that surprises you. Placebos have a role in nearly every single medical experiment--there should be more data on this subject than just about any other in medicine!

Anyhow, in conclusion you admit acute stress can have a small suppressive effect on the immune system (so methods of reducing stress can help remove this suppression) so taking that into account, I can imagine a variety of "non woo" possibilities which might seem, on the face of it, almost mystical, but could be entirely scientifically validated. Just for instance, perhaps "normal stress levels" (which in the modern day are probably very high by historical standards) create a large supressive effect that most people suffer under, and if one could learn to create a state of mind so utterly stress free, it would unleash powerful benefits to the immune system. Which brings us right back to the shark.

[fls]

fls:

You asked "How would I know that "

My answer, although perhaps misguided, is that in all the studies involving topical creams that I examined the test was to compare an inert cream with one containing the medicine. If the placebo effect was impossible when it comes to viral-immune responses then the application of the placebo cream could be eliminated, and doctors should feel comfortable comparing their proposed medicine with untreated warts.

I see. It turns out that we continue to be surprised at just how much our subjective perceptions influence what would appear to be something that is measured objectively, such as the presence or absence of a wart. Continued use of placebos helps guard against that.

Your most important question was [i]Can you give an example of some research where the impact from this state of mind has been measured? and my answer is "Not off hand but if I can locate it I will certainly share it." Your tone indicates to me that you are skeptical that any such legitimate research exists--and if you're right then what can I say, other than that I was wrong? However I boldly predict that I'll be able to come back with something that surprises you. Placebos have a role in nearly every single medical experiment--there should be more data on this subject than just about any other in medicine!

Not skeptical, but wanting to get a clearer idea of what you think illustrates the state-of-mind effect.

Anyhow, in conclusion you admit acute stress can have a small suppressive effect on the immune system (so methods of reducing stress can help remove this suppression) so taking that into account, I can imagine a variety of "non woo" possibilities which might seem, on the face of it, almost mystical, but could be entirely scientifically validated. Just for instance, perhaps "normal stress levels" (which in the modern day are probably very high by historical standards) create a large supressive effect that most people suffer under, and if one could learn to create a state of mind so utterly stress free, it would unleash powerful benefits to the immune system. Which brings us right back to the shark.

Sorry, that one doesn't fly. The system doesn't really work that way.

Linda

[Jeff Corey]

... I can imagine a variety of "non woo" possibilities which might seem, on the face of it, almost mystical, but could be entirely scientifically validated. Just for instance, perhaps "normal stress levels" (which in the modern day are probably very high by historical standards) ...
Can't you see that that is not ever possible of being scientifically validated (whatever that means)?
I wonder what the stress level of an European peasant dying of the Black Death, while trying to save her babies was, maybe less than the victims of the Spanish Inquisition or the Rape of Nanking. Or are you talking about the stress of Tiffany Soccermom when there are so many SUVs on the road that she can't get to her psychotherapist on time?

[blutoski]

Can't you see that that is not ever possible of being scientifically validated (whatever that means)?
I wonder what the stress level of an European peasant dying of the Black Death, while trying to save her babies was, maybe less than the victims of the Spanish Inquisition or the Rape of Nanking. Or are you talking about the stress of Tiffany Soccermom when there are so many SUVs on the road that she can't get to her psychotherapist on time?

There are stress indexes used in psychology that are somewhat standardized for this purpose. The one I've seen used most frequently is the Elder Life Stress Index (ELSI). It scores premature death of spouse as the most stressful event, for example. There is also the important distinction between egocentric vs nonegocentric (external) stress.

Using this and simiarl indices, it has been proposed that we are in the lowest-stress era of human history.

(I sort of wear two hats: not only do I have a degree in immunology, I also have a degree in family psychology, and stress levels are relevant to treatment planning in both fields.)

[blutoski]

A few years ago I had a common wart on my foot, I did a little research and found that it was the virus called papilloma, and that it's very common, not particularly harmful, and curable using a brute-force method of killing millions of skin cells, both healthy and infected, until you force it into remission.

But here's what made my jaw hit the floor... I was reading up on a variety of experimental cures for papilloma virus, and what I discovered is that in all of the experiments they would compare the effects of a salve (containing the experimental medicine) against a salve that contains only inert ingrediants. "Why don't they simply compare a wart treated with the salve, to a wart not treated whatsoever?" I thought to myself. The answer was simple: because even a salve containing inert ingrediants will kill the papilloma virus if the patient believes that the salve might help.

Or that your assumption about an 'inert' salve is unfounded.

Or that you're forgetting that some untreated warts see improvement.

The only way to see if the application of inert salve is actually making a difference is to compare against a non-treatment group. Until you have that extra control group, there are too many variables to conclude that belief is the only mechanism of action.




Now I can easily see why a headache medicine might show positive benefits even if it is inert. The person's mind might fool itself into relieving pain, because of the expectation of pain relief. But a virus, on one's foot? What 'state of mind' enables our feet to fight off a virus more effectively? It's positively mind-blowing.

Headache is different than wart progress: only the latter is objectively verifiable.

[blutoski]

My answer, although perhaps misguided, is that in all the studies involving topical creams that I examined the test was to compare an inert cream with one containing the medicine. If the placebo effect was impossible when it comes to viral-immune responses then the application of the placebo cream could be eliminated, and doctors should feel comfortable comparing their proposed medicine with untreated warts. However, it could be argued that this practice is just done out of convention rather than necessity, and furthermore you presented another interesting argument about bias of study groups.

I think you have it backwards: the point of a placebo control is that it should differ in only one way from the test substance. If the test substance needs to be embedded in a starch-matrix tablet or salve, then it is appropriate to assure that the placebo is as closely matched as possible, so the measured difference between the two groups' results can be attributed to the one different ingredient only.

In the background, there are a zillion unknowns that influence outcomes: the timing of the condition's cycle, the chemical effects of the additional ingredients, &c.

It's not just a convention to match placebo as closely as possible - it's the culmination of all the mistakes we've had to make through millennias of sloppy procedures.

[blutoski]

Hi everybody,

In regards to the placebo effect, I'm curious to know how often the response occurs. Do we have a lot of documented information on how often the placebo effect occurs for every condition? I'm guessing that for one illness it may be 30%, for another it may be 35%.. are there illnesses where the placebo effect could be really low, like less than 5%, like for cancer? I'm guessing we have a ton of information in regards to this since all the pharmaceutical drug testing is placebo-controlled. Which also makes me wonder how much stronger does a drug have to be than a placebo to be determined effective? If 50% of depressed people aren't depressed anymore after 3 months, and 55% of depressed people aren't depressed anymore after 3 months of taking drug XYZ, is that enough to prove it is effective? Anyway, it's just a topic that really intrigues me, any interesting facts or tidbits would be appreciated. Thanks.

In your example above, I would say that it depends just as much on the study design and statistical power. For example, if the sample size is too small to drop below p<.05, then we can't say it 'works' even if the control group had 0% improvement compared to 55% experimental group improvement.

Assuming a p<.05, then the 55% vs 50% is suggests efficacy. You would want more than one study to increase confidence in the efficacy claim before changing prescribing patterns. You would also want to compare it against existing antidepressants' efficacy to see if a 50 vs 55% improvement is better than what's currently being offered.


As to overall pattern, there is no 'knowledge' about this, since the same experiment run twice will probably have different baseline results. The effect is not predictable, and is almost always considered an artefact of the experiment, rather than a reflection of any actual clinically-relevant effect on the illness caused by treatement.