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

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 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 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.