Placebo Effect and Adherence

[Guest guest]

http://www.readability.com/mobile/articles/lfcqfzav

brodyhooked.blogspot.com

Placebo Effect and Adherence

by Brody | Sept. 3, 2011

As all four of the regular readers of this blog are aware, I am an avid listener

to Rick Bukata's and Jerry Hoffman's monthly audio recordings, Primary Care

Medical Abstracts (free advertising for them:

www.ccme.org). So here I am all innocently driving my car and listening to the

CD for their August 2011 issue, when I am shocked to hear the CD shouting out my

name. Jerry is asking that I respond to a query about one of the papers he and

Rick had been discussing, in my capacity as someone who has a long-standing

interest in the placebo effect.

So here is my answer to Jerry. You'll naturally wonder why it's here on this

blog which is about ethics and Pharma and not about placebo effect. In the end

I'll suggest an important connection.

The paper that started all this is a thoughtful editorial by

(subscription required) about the placebo effect and adherence. There have now

been a good number of studies that show that when you do a double-blind trial

with a placebo arm, there is quite often (indeed rather consistently) a

significant improvement of outcomes among those who take their placebos

faithfully, compared to those who are relatively non-adherent to taking their

placebos. does a neat analysis of what we know, and what we don't yet

know, about this adherence phenomenon, and suggests linkages to what we are

learning about placebo effects and why this phenomenon might be viewed (at least

as a working hypothesis) as a variant of placebo effect.

Jerry then raises the question: what's the message here for clinicians? Should

we give patients pep talks to try to both encourage and energize them about the

treatments we're prescribing (whether drug or nondrug) to try to enhance their

expectations of a good outcome, which has been shown to be positively associated

with a placebo response? Should this pep talk include advice to be sure to take

their pills (or other treatments) faithfully? Or might it be the case that the

adherence research shows that what really matters is what's already inside the

patient's head, not what we say--that those in the trials that were more

adherent were simply that sort of person, and being that sort of person is what

matters in terms of triggering a placebo effect--and our pep talk is worthless?

OK, Jerry, here's my answer, followed by my hunch.

My answer, as 's nice review suggests, is: we don't know. No one has yet

done the sort of fine-grained study of the more-adherent research subjects,

analogous to some of the latest generation of placebo-effect research done in

the last decade with brain imaging etc. So the underlying psychological and

neurochemical factors that might explain the adherence-placebo effect link are

unknown.

Now my hunch. The placebo effect is almost certainly multifactorial. Indeed,

Fabrizio Benedetti of Turin titled his excellent 2009 book Placebo Effects

(rather than Placebo Effect) to make the argument that continued research will

almost certainly reveal multiple underlying mechanisms that may operate in

different diseases and different organ systems.

The best available evidence that we have suggests two very general psychological

mechanisms for most placebo effects--expectancy and conditioning. Expectancy is

basically forward looking--your body is likely to heal itself when you think it

will get better in the future. Conditioning is backward--your body is more

likely to heal itself when you associate the circumstances you're in now with

circumstances in which your body experienced healing previously.

The adherence effect probably partakes of both. Subjects who take their

medicines regularly probably anticipate a good outcome with greater confidence.

These same people probably got better in the past when they religiously took

their pills, and so conditioning can contribute to their getting better this

time by reactivating the same neural pathways.

Now what happens if a physician acts enthusiastic and encouraging about the

nature of the treatment? This is likely to increase both expectancy and

conditioning effects--expectancy for obvious reasons, conditioning because the

patient probably associates an emotionally supportive environment with past

healing (going as far back as when Mommy kissed your boo-boo and it got better

afterwards). So I cannot see how the encouraging physician could detract in any

way from the patient's inner tendency to experience an adherence-placebo

reaction, and I can see several ways that the former might enhance the latter.

So: bring on the pep-talk.

I have recently become interested in the connection between placebo response and

medicine viewed as ritual/performance/theater. We scientific types are used to

dismissing ritual as meaningless superstition, but the current placebo research

indicates the neuroanatomical and neurochemical reasons why ritual can be

efficacious in changing bodily function as well as in altering our cognitive and

emotional views of the world. Much of medicine, when we think about it, is

ritual and/or performance. (Science writer Wade once wrote something

like, " All medicine is a form of theater. " ) Rituals include taking one's pills

once or several times a day and can readily trigger both expectancy and

conditioning responses. Smart physicians who prescribe exercise and other

lifestyle changes try whever possible to suggest rituals to patients to increase

adherence, in some cases going so far as to write the instructions on a

prescription pad, which when in practice I always found especially powerful. All

of these measures seem well calculated to increase placebo effects, as well as

to make patients healthier by way of the drug or the exercise or whatever.

I promised in the end to bring this back around to Pharma, so here goes. I

suggest that you read 's article and look especially at the effect sizes

reported for the adherence-placebo effect. Just for example: Mortality

difference between adherent and nonadherent placebo group subjects in the

Coronary Drug Project (1980): 15% vs. 25%. More recently, adherence effect in

mortality in heart failure, based on the SOLV-TT and SOLV-PT trials: hazard

ratio 0.52 (Avins 2010). And remember, according to the body of data

reviews, these are not one-time flukes. And remember too we are talking here

about people keeling over dead, not some meaningless surrogate endpoint.

Why is this of importance? The drug companies would kill to come up with a new

drug that had efficacy numbers this good. So you could spin this in a pro- or

anti-industry fashion. On the side of the industry, have a pity--look what they

have to overcome to show that a new drug is better than placebo, when the

placebo effect alone can be this powerful. But on the other side of the coin,

when mere encouragement and positive thinking can have this much beneficial

effect on patient outcomes, why in heaven's name would we want to give drugs

that have dangerous side effects and that cost an arm and a leg, unless the

drugs had been clearly shown to be really superior to cheap and safe

encouragement?

IB. Adherence, placebo effects, amd mortality [editorial]. Journal of

General Internal Medicine 25:1270-1272, December 2010.

Avins AL, Pressman A, Ackerson L, et al. Placebo adherence and its association

with morbidity and mortality in the studies of left ventricular dysfunction.

Journal of General Internal Medicine 25: 1275-1281, December 2010.

Sent via BlackBerry by AT & T

[Guest guest]

http://www.readability.com/mobile/articles/lfcqfzav

brodyhooked.blogspot.com

Placebo Effect and Adherence

by Brody | Sept. 3, 2011

As all four of the regular readers of this blog are aware, I am an avid listener

to Rick Bukata's and Jerry Hoffman's monthly audio recordings, Primary Care

Medical Abstracts (free advertising for them:

www.ccme.org). So here I am all innocently driving my car and listening to the

CD for their August 2011 issue, when I am shocked to hear the CD shouting out my

name. Jerry is asking that I respond to a query about one of the papers he and

Rick had been discussing, in my capacity as someone who has a long-standing

interest in the placebo effect.

So here is my answer to Jerry. You'll naturally wonder why it's here on this

blog which is about ethics and Pharma and not about placebo effect. In the end

I'll suggest an important connection.

The paper that started all this is a thoughtful editorial by

(subscription required) about the placebo effect and adherence. There have now

been a good number of studies that show that when you do a double-blind trial

with a placebo arm, there is quite often (indeed rather consistently) a

significant improvement of outcomes among those who take their placebos

faithfully, compared to those who are relatively non-adherent to taking their

placebos. does a neat analysis of what we know, and what we don't yet

know, about this adherence phenomenon, and suggests linkages to what we are

learning about placebo effects and why this phenomenon might be viewed (at least

as a working hypothesis) as a variant of placebo effect.

Jerry then raises the question: what's the message here for clinicians? Should

we give patients pep talks to try to both encourage and energize them about the

treatments we're prescribing (whether drug or nondrug) to try to enhance their

expectations of a good outcome, which has been shown to be positively associated

with a placebo response? Should this pep talk include advice to be sure to take

their pills (or other treatments) faithfully? Or might it be the case that the

adherence research shows that what really matters is what's already inside the

patient's head, not what we say--that those in the trials that were more

adherent were simply that sort of person, and being that sort of person is what

matters in terms of triggering a placebo effect--and our pep talk is worthless?

OK, Jerry, here's my answer, followed by my hunch.

My answer, as 's nice review suggests, is: we don't know. No one has yet

done the sort of fine-grained study of the more-adherent research subjects,

analogous to some of the latest generation of placebo-effect research done in

the last decade with brain imaging etc. So the underlying psychological and

neurochemical factors that might explain the adherence-placebo effect link are

unknown.

Now my hunch. The placebo effect is almost certainly multifactorial. Indeed,

Fabrizio Benedetti of Turin titled his excellent 2009 book Placebo Effects

(rather than Placebo Effect) to make the argument that continued research will

almost certainly reveal multiple underlying mechanisms that may operate in

different diseases and different organ systems.

The best available evidence that we have suggests two very general psychological

mechanisms for most placebo effects--expectancy and conditioning. Expectancy is

basically forward looking--your body is likely to heal itself when you think it

will get better in the future. Conditioning is backward--your body is more

likely to heal itself when you associate the circumstances you're in now with

circumstances in which your body experienced healing previously.

The adherence effect probably partakes of both. Subjects who take their

medicines regularly probably anticipate a good outcome with greater confidence.

These same people probably got better in the past when they religiously took

their pills, and so conditioning can contribute to their getting better this

time by reactivating the same neural pathways.

Now what happens if a physician acts enthusiastic and encouraging about the

nature of the treatment? This is likely to increase both expectancy and

conditioning effects--expectancy for obvious reasons, conditioning because the

patient probably associates an emotionally supportive environment with past

healing (going as far back as when Mommy kissed your boo-boo and it got better

afterwards). So I cannot see how the encouraging physician could detract in any

way from the patient's inner tendency to experience an adherence-placebo

reaction, and I can see several ways that the former might enhance the latter.

So: bring on the pep-talk.

I have recently become interested in the connection between placebo response and

medicine viewed as ritual/performance/theater. We scientific types are used to

dismissing ritual as meaningless superstition, but the current placebo research

indicates the neuroanatomical and neurochemical reasons why ritual can be

efficacious in changing bodily function as well as in altering our cognitive and

emotional views of the world. Much of medicine, when we think about it, is

ritual and/or performance. (Science writer Wade once wrote something

like, " All medicine is a form of theater. " ) Rituals include taking one's pills

once or several times a day and can readily trigger both expectancy and

conditioning responses. Smart physicians who prescribe exercise and other

lifestyle changes try whever possible to suggest rituals to patients to increase

adherence, in some cases going so far as to write the instructions on a

prescription pad, which when in practice I always found especially powerful. All

of these measures seem well calculated to increase placebo effects, as well as

to make patients healthier by way of the drug or the exercise or whatever.

I promised in the end to bring this back around to Pharma, so here goes. I

suggest that you read 's article and look especially at the effect sizes

reported for the adherence-placebo effect. Just for example: Mortality

difference between adherent and nonadherent placebo group subjects in the

Coronary Drug Project (1980): 15% vs. 25%. More recently, adherence effect in

mortality in heart failure, based on the SOLV-TT and SOLV-PT trials: hazard

ratio 0.52 (Avins 2010). And remember, according to the body of data

reviews, these are not one-time flukes. And remember too we are talking here

about people keeling over dead, not some meaningless surrogate endpoint.

Why is this of importance? The drug companies would kill to come up with a new

drug that had efficacy numbers this good. So you could spin this in a pro- or

anti-industry fashion. On the side of the industry, have a pity--look what they

have to overcome to show that a new drug is better than placebo, when the

placebo effect alone can be this powerful. But on the other side of the coin,

when mere encouragement and positive thinking can have this much beneficial

effect on patient outcomes, why in heaven's name would we want to give drugs

that have dangerous side effects and that cost an arm and a leg, unless the

drugs had been clearly shown to be really superior to cheap and safe

encouragement?

IB. Adherence, placebo effects, amd mortality [editorial]. Journal of

General Internal Medicine 25:1270-1272, December 2010.

Avins AL, Pressman A, Ackerson L, et al. Placebo adherence and its association

with morbidity and mortality in the studies of left ventricular dysfunction.

Journal of General Internal Medicine 25: 1275-1281, December 2010.

Sent via BlackBerry by AT & T

[Guest guest]

http://www.readability.com/mobile/articles/lfcqfzav

brodyhooked.blogspot.com

Placebo Effect and Adherence

by Brody | Sept. 3, 2011

As all four of the regular readers of this blog are aware, I am an avid listener

to Rick Bukata's and Jerry Hoffman's monthly audio recordings, Primary Care

Medical Abstracts (free advertising for them:

www.ccme.org). So here I am all innocently driving my car and listening to the

CD for their August 2011 issue, when I am shocked to hear the CD shouting out my

name. Jerry is asking that I respond to a query about one of the papers he and

Rick had been discussing, in my capacity as someone who has a long-standing

interest in the placebo effect.

So here is my answer to Jerry. You'll naturally wonder why it's here on this

blog which is about ethics and Pharma and not about placebo effect. In the end

I'll suggest an important connection.

The paper that started all this is a thoughtful editorial by

(subscription required) about the placebo effect and adherence. There have now

been a good number of studies that show that when you do a double-blind trial

with a placebo arm, there is quite often (indeed rather consistently) a

significant improvement of outcomes among those who take their placebos

faithfully, compared to those who are relatively non-adherent to taking their

placebos. does a neat analysis of what we know, and what we don't yet

know, about this adherence phenomenon, and suggests linkages to what we are

learning about placebo effects and why this phenomenon might be viewed (at least

as a working hypothesis) as a variant of placebo effect.

Jerry then raises the question: what's the message here for clinicians? Should

we give patients pep talks to try to both encourage and energize them about the

treatments we're prescribing (whether drug or nondrug) to try to enhance their

expectations of a good outcome, which has been shown to be positively associated

with a placebo response? Should this pep talk include advice to be sure to take

their pills (or other treatments) faithfully? Or might it be the case that the

adherence research shows that what really matters is what's already inside the

patient's head, not what we say--that those in the trials that were more

adherent were simply that sort of person, and being that sort of person is what

matters in terms of triggering a placebo effect--and our pep talk is worthless?

OK, Jerry, here's my answer, followed by my hunch.

My answer, as 's nice review suggests, is: we don't know. No one has yet

done the sort of fine-grained study of the more-adherent research subjects,

analogous to some of the latest generation of placebo-effect research done in

the last decade with brain imaging etc. So the underlying psychological and

neurochemical factors that might explain the adherence-placebo effect link are

unknown.

Now my hunch. The placebo effect is almost certainly multifactorial. Indeed,

Fabrizio Benedetti of Turin titled his excellent 2009 book Placebo Effects

(rather than Placebo Effect) to make the argument that continued research will

almost certainly reveal multiple underlying mechanisms that may operate in

different diseases and different organ systems.

The best available evidence that we have suggests two very general psychological

mechanisms for most placebo effects--expectancy and conditioning. Expectancy is

basically forward looking--your body is likely to heal itself when you think it

will get better in the future. Conditioning is backward--your body is more

likely to heal itself when you associate the circumstances you're in now with

circumstances in which your body experienced healing previously.

The adherence effect probably partakes of both. Subjects who take their

medicines regularly probably anticipate a good outcome with greater confidence.

These same people probably got better in the past when they religiously took

their pills, and so conditioning can contribute to their getting better this

time by reactivating the same neural pathways.

Now what happens if a physician acts enthusiastic and encouraging about the

nature of the treatment? This is likely to increase both expectancy and

conditioning effects--expectancy for obvious reasons, conditioning because the

patient probably associates an emotionally supportive environment with past

healing (going as far back as when Mommy kissed your boo-boo and it got better

afterwards). So I cannot see how the encouraging physician could detract in any

way from the patient's inner tendency to experience an adherence-placebo

reaction, and I can see several ways that the former might enhance the latter.

So: bring on the pep-talk.

I have recently become interested in the connection between placebo response and

medicine viewed as ritual/performance/theater. We scientific types are used to

dismissing ritual as meaningless superstition, but the current placebo research

indicates the neuroanatomical and neurochemical reasons why ritual can be

efficacious in changing bodily function as well as in altering our cognitive and

emotional views of the world. Much of medicine, when we think about it, is

ritual and/or performance. (Science writer Wade once wrote something

like, " All medicine is a form of theater. " ) Rituals include taking one's pills

once or several times a day and can readily trigger both expectancy and

conditioning responses. Smart physicians who prescribe exercise and other

lifestyle changes try whever possible to suggest rituals to patients to increase

adherence, in some cases going so far as to write the instructions on a

prescription pad, which when in practice I always found especially powerful. All

of these measures seem well calculated to increase placebo effects, as well as

to make patients healthier by way of the drug or the exercise or whatever.

I promised in the end to bring this back around to Pharma, so here goes. I

suggest that you read 's article and look especially at the effect sizes

reported for the adherence-placebo effect. Just for example: Mortality

difference between adherent and nonadherent placebo group subjects in the

Coronary Drug Project (1980): 15% vs. 25%. More recently, adherence effect in

mortality in heart failure, based on the SOLV-TT and SOLV-PT trials: hazard

ratio 0.52 (Avins 2010). And remember, according to the body of data

reviews, these are not one-time flukes. And remember too we are talking here

about people keeling over dead, not some meaningless surrogate endpoint.

Why is this of importance? The drug companies would kill to come up with a new

drug that had efficacy numbers this good. So you could spin this in a pro- or

anti-industry fashion. On the side of the industry, have a pity--look what they

have to overcome to show that a new drug is better than placebo, when the

placebo effect alone can be this powerful. But on the other side of the coin,

when mere encouragement and positive thinking can have this much beneficial

effect on patient outcomes, why in heaven's name would we want to give drugs

that have dangerous side effects and that cost an arm and a leg, unless the

drugs had been clearly shown to be really superior to cheap and safe

encouragement?

IB. Adherence, placebo effects, amd mortality [editorial]. Journal of

General Internal Medicine 25:1270-1272, December 2010.

Avins AL, Pressman A, Ackerson L, et al. Placebo adherence and its association

with morbidity and mortality in the studies of left ventricular dysfunction.

Journal of General Internal Medicine 25: 1275-1281, December 2010.

Sent via BlackBerry by AT & T

[Guest guest]

http://www.readability.com/mobile/articles/lfcqfzav

brodyhooked.blogspot.com

Placebo Effect and Adherence

by Brody | Sept. 3, 2011

As all four of the regular readers of this blog are aware, I am an avid listener

to Rick Bukata's and Jerry Hoffman's monthly audio recordings, Primary Care

Medical Abstracts (free advertising for them:

www.ccme.org). So here I am all innocently driving my car and listening to the

CD for their August 2011 issue, when I am shocked to hear the CD shouting out my

name. Jerry is asking that I respond to a query about one of the papers he and

Rick had been discussing, in my capacity as someone who has a long-standing

interest in the placebo effect.

So here is my answer to Jerry. You'll naturally wonder why it's here on this

blog which is about ethics and Pharma and not about placebo effect. In the end

I'll suggest an important connection.

The paper that started all this is a thoughtful editorial by

(subscription required) about the placebo effect and adherence. There have now

been a good number of studies that show that when you do a double-blind trial

with a placebo arm, there is quite often (indeed rather consistently) a

significant improvement of outcomes among those who take their placebos

faithfully, compared to those who are relatively non-adherent to taking their

placebos. does a neat analysis of what we know, and what we don't yet

know, about this adherence phenomenon, and suggests linkages to what we are

learning about placebo effects and why this phenomenon might be viewed (at least

as a working hypothesis) as a variant of placebo effect.

Jerry then raises the question: what's the message here for clinicians? Should

we give patients pep talks to try to both encourage and energize them about the

treatments we're prescribing (whether drug or nondrug) to try to enhance their

expectations of a good outcome, which has been shown to be positively associated

with a placebo response? Should this pep talk include advice to be sure to take

their pills (or other treatments) faithfully? Or might it be the case that the

adherence research shows that what really matters is what's already inside the

patient's head, not what we say--that those in the trials that were more

adherent were simply that sort of person, and being that sort of person is what

matters in terms of triggering a placebo effect--and our pep talk is worthless?

OK, Jerry, here's my answer, followed by my hunch.

My answer, as 's nice review suggests, is: we don't know. No one has yet

done the sort of fine-grained study of the more-adherent research subjects,

analogous to some of the latest generation of placebo-effect research done in

the last decade with brain imaging etc. So the underlying psychological and

neurochemical factors that might explain the adherence-placebo effect link are

unknown.

Now my hunch. The placebo effect is almost certainly multifactorial. Indeed,

Fabrizio Benedetti of Turin titled his excellent 2009 book Placebo Effects

(rather than Placebo Effect) to make the argument that continued research will

almost certainly reveal multiple underlying mechanisms that may operate in

different diseases and different organ systems.

The best available evidence that we have suggests two very general psychological

mechanisms for most placebo effects--expectancy and conditioning. Expectancy is

basically forward looking--your body is likely to heal itself when you think it

will get better in the future. Conditioning is backward--your body is more

likely to heal itself when you associate the circumstances you're in now with

circumstances in which your body experienced healing previously.

The adherence effect probably partakes of both. Subjects who take their

medicines regularly probably anticipate a good outcome with greater confidence.

These same people probably got better in the past when they religiously took

their pills, and so conditioning can contribute to their getting better this

time by reactivating the same neural pathways.

Now what happens if a physician acts enthusiastic and encouraging about the

nature of the treatment? This is likely to increase both expectancy and

conditioning effects--expectancy for obvious reasons, conditioning because the

patient probably associates an emotionally supportive environment with past

healing (going as far back as when Mommy kissed your boo-boo and it got better

afterwards). So I cannot see how the encouraging physician could detract in any

way from the patient's inner tendency to experience an adherence-placebo

reaction, and I can see several ways that the former might enhance the latter.

So: bring on the pep-talk.

I have recently become interested in the connection between placebo response and

medicine viewed as ritual/performance/theater. We scientific types are used to

dismissing ritual as meaningless superstition, but the current placebo research

indicates the neuroanatomical and neurochemical reasons why ritual can be

efficacious in changing bodily function as well as in altering our cognitive and

emotional views of the world. Much of medicine, when we think about it, is

ritual and/or performance. (Science writer Wade once wrote something

like, " All medicine is a form of theater. " ) Rituals include taking one's pills

once or several times a day and can readily trigger both expectancy and

conditioning responses. Smart physicians who prescribe exercise and other

lifestyle changes try whever possible to suggest rituals to patients to increase

adherence, in some cases going so far as to write the instructions on a

prescription pad, which when in practice I always found especially powerful. All

of these measures seem well calculated to increase placebo effects, as well as

to make patients healthier by way of the drug or the exercise or whatever.

I promised in the end to bring this back around to Pharma, so here goes. I

suggest that you read 's article and look especially at the effect sizes

reported for the adherence-placebo effect. Just for example: Mortality

difference between adherent and nonadherent placebo group subjects in the

Coronary Drug Project (1980): 15% vs. 25%. More recently, adherence effect in

mortality in heart failure, based on the SOLV-TT and SOLV-PT trials: hazard

ratio 0.52 (Avins 2010). And remember, according to the body of data

reviews, these are not one-time flukes. And remember too we are talking here

about people keeling over dead, not some meaningless surrogate endpoint.

Why is this of importance? The drug companies would kill to come up with a new

drug that had efficacy numbers this good. So you could spin this in a pro- or

anti-industry fashion. On the side of the industry, have a pity--look what they

have to overcome to show that a new drug is better than placebo, when the

placebo effect alone can be this powerful. But on the other side of the coin,

when mere encouragement and positive thinking can have this much beneficial

effect on patient outcomes, why in heaven's name would we want to give drugs

that have dangerous side effects and that cost an arm and a leg, unless the

drugs had been clearly shown to be really superior to cheap and safe

encouragement?

IB. Adherence, placebo effects, amd mortality [editorial]. Journal of

General Internal Medicine 25:1270-1272, December 2010.

Avins AL, Pressman A, Ackerson L, et al. Placebo adherence and its association

with morbidity and mortality in the studies of left ventricular dysfunction.

Journal of General Internal Medicine 25: 1275-1281, December 2010.

Sent via BlackBerry by AT & T