National Ethics Teleconference

*Clinical Use of Placebo: An Ethics Analysis*

## July 28, 2004

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# 

# INTRODUCTION

**Dr. Berkowitz:**

Good day everyone. This is Ken Berkowitz. I am the Chief of the Ethics
Consultation Service at the VHA National Center for Ethics in Health
Care and a physician at the VA NY Harbor Healthcare System. I am very
pleased to welcome you all to today\'s National Ethics Teleconference.
By sponsoring this series of calls, the Center provides an opportunity
for regular education and open discussion of ethical concerns relevant
to VHA. Each call features an educational presentation on an interesting
ethics topic followed by an open, moderated discussion of that topic.
After the discussion, we reserve the last few minutes of each call for
our \'from the field section\'. This will be your opportunity to speak
up and let us know what is on your mind regarding ethics related topics
other than the focus of today\'s call.

# PRESENTATION

**Dr. Berkowitz:**

Today's presentation will focus on the ethical dimensions of using
placebo in clinical care. Joining me on today's call is Tim Sutton a
summer ethics intern at our Center's New York office, who recently
completed his master's degree in Bioethics at Case Western Reserve
University.

The Ethics Center has received a number of consults from the field
related to the ethical issues related to the clinical use of placebo.
One involved a patient who learned that his prescribed pain medication
-- Obecalp -- was really placebo spelled backwards. The patient was
angry that his physician deceived him, and his relationship with his
physician broke down completely. Another case involved a physician
deceptively using Tylenol as a treatment for anxiety in a difficult
patient. But we thought we'd start our presentation by presenting a
hypothetical case that was adapted from a 1998 article from the Journal
of Ethics and Behavior by Blustein et al, entitled "Case Vignette:
Placebos and Informed Consent." Consider Michael, a 45-year-old male
with chronic back pain that has limited his ability to work. A
neurological evaluation did not reveal any serious abnormalities. He has
had physical therapy, chiropractic manipulations, acupuncture, and a
range of narcotic and anti-inflammatory treatments. Michael was referred
to the pain clinic. After carefully examining Michael and reviewing his
records, Dr. Davis told him about a medicine that he generally reserves
for complex pain. Although there may be some side effects he encouraged
the patient to try it because he believed it could work. The prescribed
substance was a placebo.

Three weeks following his initial visit, Michael noted improvement in
his pain, but subsequently learned by searching WebMD that his
medication was a sugar pill commonly prescribed as a placebo. Feeling
confused and betrayed, Michael never returned to see Dr. Davis.

This dramatic hypothetical is a good example of what's at stake with the
clinical use of placebos. Tim, would you begin by telling us what a
placebo is, and the ethical issues involved in its use?

**Mr. Sutton:**

First, let me offer a couple of definitions. For our discussion, we will
define a placebo as a substance with no known clinical use for the
condition being addressed. The placebo effect is defined in the
Encyclopedia of Bioethics as a "change in a patient's condition that
results from the symbolic aspects of the encounter with a healer or with
a healing setting, and not from the pharmacological or physiological
properties of any remedy used." Placebo use falls into two main
contexts, clinical care and research. On today's call, we will limit our
discussion to the clinical use of placebo, though much of what we know
about placebos comes from their use in clinical trials.

Before the modern era of pharmacology, questions about placebos centered
on whether or not placebos were more effective for controlling symptoms
than no treatment. While this is still an important question today, we
have effective treatments for most symptoms, and so, ethical concerns
around the clinical use of placebos have changed. Currently, I think the
central ethical conflict in the clinical use of placebos as one of
truth-telling versus beneficence. Acknowledging that patients are
generally told the truth and included in meaningfully decision-making,
what do we do if we genuinely feel that the patient would be better off
not knowing? From this tension, several key questions arise. Is it
ethical for physicians to use a mode of treatment that involves lying to
the patient? Is this deception justifiable by the good that it will do
for the patient? If so, is there evidence of efficacy to justify such
use of a placebo? Does non-disclosure of such treatment undermine trust
in the physician-patient relationship if it is discovered?

**Dr. Berkowitz:**

Let's start by discussing the importance of truth-telling in the
provider patient relationship.

**Mr. Sutton:**

Before the evolution of shared decision-making and informed consent
practices over the latter half of the 20^th^ century, truth-telling was
not considered nearly as important as it is today. Physicians were
trusted to make clinical decisions based on the patient's best interest.
If they believed certain information might be damaging to a patient,
they would withhold it. If they believed a placebo was medically
appropriate, they would administer it. Disclosure, as we know it today,
was not a standard part of practice, so deception was not considered a
significant issue. In fact, neither the Declaration of Geneva of the
World Medical Association, nor the Oath of Maimonides, nor the
Hippocratic Oath even address truth-telling.

Over the past several decades, the medical profession has evolved past
paternalism to a provider-patient model based much more on patient
autonomy. Now, health care decision-making is a shared enterprise
between the practitioner and patient, with the patient having final
choice between medically acceptable options (including refusal of any
treatment).

**Dr. Berkowitz:**

Honesty fosters trust, which is why it is a cornerstone of the
physician-patient relationship. Without the honest exchange of
information, patients can't participate in the shared decision-making
process, which is an essential component of quality in health care
delivery.

Can you elaborate further on the potential harms from administering
placebo deceptively?

**Mr. Sutton:**

One potential harm in administering a placebo is loss of trust in the
patient provider relationship when deception is discovered. Increased
public awareness, personal interest in health, and the availability of
information from the internet and other sources have reduced the
likelihood that a clinician is capable of maintaining such a deception
-- not that it would be justified even then. Also, in today's
multi-disciplinary approach to health care, it would require a
conspiracy for all practitioners to consistently deceive a patient. If
and when the patient finds out about the placebo, not only will the
potential clinical benefit be lost, but the patient will lose trust in
the provider and perhaps the delivery system itself.

**Dr. Berkowitz:**

Another question is whether placebos meet the needs of the patients for
whom they are prescribed. Let's turn back to our case example for a
moment. Although a specific symptom, pain, was what originally motivated
the patient in the case to come to the clinic, his goals probably also
included a diagnostic work-up and, hopefully, a treatment for the cause
of the pain if possible. Walter Robinson argued in the 1998 Ethics and
Behavior article that "patients seek help in an environment that should
not only address symptoms, but investigate their causes, match therapy
both to the conditions and the patient's life, and explore the full
meanings of the conditions within the context of the patient's history
and experiences." Prescribing a placebo addresses only the most
superficial layer of patient need. Therefore, relying on placebo before
all other therapeutic modalities are exhausted is an unjustifiable
model.

**Mr. Sutton:**

Robinson also argued that clinicians who prescribe a placebo misperceive
their professional role by viewing themselves as the sole source of
healing. This changes the balance in the provider-patient relationship
to the point where the patient is no longer treated as a partner in
health care decision-making.

**Dr. Berkowitz:**

And if using a placebo denies patients a real chance for diagnosis and
other treatment that would be unacceptable.

Tim, the most common clinical use of placebo today is probably for the
treatment of pain. Can you tell us more about this worrisome practice?

**Mr. Sutton:**

One of the more common uses of placebo is as a diagnostic tool to
distinguish between organic and functional conditions, or determine
whether a patient's pain is "real." Pain is a multifaceted phenomenon
that is, by its very nature, subjective. A positive placebo response,
therefore, tells nothing about the cause of a patient's pain, and
misinterpreting a response can extinguish any hope of securing
appropriate evaluation and treatment for patients with complex pain
problems. Thus, placebo should not be used as an assessment tool for
pain. This practice is worrisome enough for the American Nurses
Association Oncology Nursing Society to develop a specific position
statement in this area. Their position is simple, and I'll quote it,
"...placebos should not be used in the assessment and management of
cancer pain."

This sentiment is shared by other organizations. The American Society
for Pain Management Nursing has a similar position statement that
asserts the society's adamant opposition to the use of placebo in the
assessment and treatment of pain in all patients.

Another fairly common misuse of placebo is using it to placate demanding
or nuisance patients. This is not an advisable practice for a couple of
reasons. First, placebo is a superficial intervention; it does not
address the root of a demanding patient's problem. Next, since we know
that pain is subjective, the standard of care is to take the patient at
his or her word. There is a real danger of increased patient suffering
if the clinician incorrectly concludes the patient is lying or simply
wants attention.

**Dr. Berkowitz:**

Labeling a patient as malingering, lying, drug seeking, attention
seeking or non-compliant is a pitfall that all practitioners have to
avoid.

But suppose for a moment that the ethical hurdles of deception in
prescribing placebo could be overcome. What is known about the clinical
efficacy of placebo?

**Mr. Sutton:**

The strongest argument for the clinical use of placebo is that some
studies have reported it to be effective, but many of these studies have
been criticized for their designs. The effectiveness is generally
compared to no treatment at all, but some studies reported that placebos
were comparable to standard therapies. Placebos have been reported to
effect around 35% of patients. Unfortunately, numerous studies to date
have failed to identify any traits or characteristics indicative of a
consistent responder.

Despite the common belief that the placebo effect is purely
psychological, it has been associated with physiological changes. In a
2004 Science and Engineering Ethics article titled "The Biochemical
Bases of the Placebo effect," Fuente-Fernandez and Stoessl found
evidence to once again support the belief that the placebo effect is
related to expectation of clinical benefit. This expectation translated
into physiological changes. They performed positron emission tomography
scans in patients with Parkinson's disease, pain, and depression. They
observed that placebo administration was associated with the release of
high levels of neurotransmitters and neuropeptides in the brain." How
these changes translate clinically is speculative.

**Dr. Berkowitz:**

But even if placebo were shown to be effective in certain cases, how
would one address the need for truthfulness?

**Mr. Sutton:**

This strikes at the very heart of the placebo debate. If one decided
that placebo is an appropriate treatment for a specific case, then it
should be subject to the informed consent process. Telling the patient
they are being prescribed a medication with no active ingredients allows
the patient to participate in deception-free shared decision-making.

**Dr. Berkowitz:**

In 2001, Hrobjartsson and Gotzsche published a meta-analysis of the
placebo effect in the New England Journal of Medicine. That article, "Is
the Placebo Powerless," suggested that the placebo effect is not as
powerful as some people believe.

In fact, Hrobjartsson's article argues that there may not be any
clinical benefit to placebo.

**Mr. Sutton:**

They conducted a systematic review of clinical trials in which patients
were randomly assigned to either a placebo or no treatment. They
analyzed 117 trials, 32 had binary outcomes and 82 had continuous
outcomes. Hrobjartsson et al concluded there is:

> little evidence in general that placebos had powerful clinical
> effects. Although placebos had no significant effects on objective or
> binary outcomes, they had possible small benefits in studies with
> continuous subjective outcomes and for the treatment of pain. The
> effect decreased with increasing sample size, however, indicating a
> possible bias related to the effects of small trials.

The researchers concluded that "outside the setting of clinical trials,
there is no justification for the use of placebo."

**Dr. Berkowitz:**

They also pointed out that since the vast majority of the studies on
placebo efficacy were designed with an approach that cannot distinguish
the effect of the placebo from the natural course of the disease. This
is clinically significant for many of the conditions studied--- nausea,
asthma, pain, etc.---all tend to naturally wax and wane. They postulate
that some of the reported effects of a placebo might be an artifact of
this inadequate research method.

Another bias that they speculate might be reflected in the placebo
literature is publication bias, that is, some trials with negative
outcomes might not have been published. Thus, any placebo efficacy found
on a meta-analysis might tend to over report such efficacy.

And again, the overall result of their review was that there was little
evidence that placebos in general have powerful clinical effects.

**Mr. Sutton:**

Not all are convinced by Hrobjartsson's meta-analysis, however. Spiegel,
Kraemer, and Carlson argued in a subsequent 2001 New England Journal
article that Hrobjartsson's conclusions do not necessarily follow from
his study. They said the technique of meta-analysis was designed for
trials addressing similar questions, which was not the case with the
studies analyzed by Hrobjartsson. Hrobjartsson used trials where the
populations varied widely, influenced by disorders and the active
treatments used. Then the collected studies were analyzed with 40
different outcome measures, some more reliable than others.

**Dr. Berkowitz:**

So far we've been talking about placebo as a sole therapy. Recently, a
literature on the use of placebo as an adjunctive therapy has begun to
emerge. Can you talk for a moment about this?

**Mr. Sutton:**

In a recent article, Nikola Biller Andorno argued that the placebo is
most appropriately used in conjunction with standard therapy, not as a
replacement for it. A 2003 clinical trial by Sandler and Bodfish seems
to support his thinking. The trial examined the feasibility and
potential effectiveness of using placebos along with unusually low doses
of stimulant medications to treat 26 children with attention deficit
hyperactivity disorder (ADHD). The results suggest that placebo might be
successfully integrated into an active medication regimen to achieve
therapeutic results with lower dosages and fewer side-effects. The
participants with ADHD did just as well with half as much medicine when
a placebo was added to their treatment. The patients who took lower
doses without the placebo had fewer side effects, but with reduced
therapeutic effect. The National Institute of Health recently provided
the researchers with a grant to expand the study and integrate pairings
of decreasing doses of stimulant medications with distinctive placebos.

**Dr. Berkowitz:**

So, while there is evidence of some sort of placebo effect, there is
still disagreement as to the clinical significance or application of
that effect.

Do you have any recommendations or final thoughts regarding the clinical
use of placebo? What questions should practitioners ask themselves
before using a placebo?

**Mr. Sutton:**

First and foremost, I'd like to say that there is no way to ethically
justify the deceptive use of placebo. Any important information that a
patient might need to make a responsible decision about his or her
medical care should not be withheld, even if withholding the information
appears to be in his or her best interest. Deception violates both
patient autonomy and the fundamental respect for persons.

**Dr. Berkowitz:**

We are committed to engaging our patients in shared decision making
about their treatments and this is clear in our policy on informed
consent. That being said, we are not aware of specific VHA policy on the
clinical use of placebo. Since we are aware that there seem to be some
practitioners in our system who still use placebo clinically, could you
comment on questions that a practitioner should ask themselves before
using a placebo clinically?

**Mr. Sutton:**

In the rare event that a practitioner is considering the clinical use of
placebo, I think that the practitioner should consider the following:

The patient's diagnosis should be reviewed and confirmed. A placebo
should never be used as a diagnostic tool. Using placebo prior to
completing the diagnostic work-up can be misleading and prevent
definitive treatment.

> A placebo should never be used before other therapies have been
> exhausted.
>
> When placebo is being considered as a treatment for symptoms believed
> to originate in mental illness, call a psychiatric evaluation instead
> to get expert advice on treating the underlying problem.
>
> Resist labeling patients and giving placebo to patients because they
> are very demanding or a nuisance.

In the rare instances where a placebo is prescribed, the patient must be
informed. Set clear expectations about what the intervention is and why
it currently seems to be the best option.

**Dr. Berkowitz:**

So to sum up, there is very little justification for the clinical use of
placebo. In the rare instance that a practitioner decides to use a
placebo, it should never be without full disclosure to the patient.

That concludes the formal presentation portion of the call. We still
have some time for discussion so please feel free to introduce yourself
and speak up. Does anyone have reactions to our presentation?

**MODERATED DISCUSSION**

**Stuart Selikowitz, MD, White River Junction VAMC:**

I have never encountered a situation in the practice, where a placebo
was given in a non-study situation, and I wonder how often placebos are
actually used.

**Dr. Berkowitz**:

I don't know of any data on that question, but I do know that it does
continue to happen through consultations we've received at the Ethics
Center.

**Ghulam Dastgeer, MD, Northampton VAMC**:

This was a practice about 20 years ago, but now, we don't see it very
often. Back then, we used to give vitamin C, or saline injections
instead of something else, but now, with the multi-disciplinary
approach, we don't do that.

**Dr. Berkowitz:**

We had a consultation recently concerning a patient in the long-term
setting who was given vitamin C, but I'm not sure in that situation it
was being used as a placebo. This was a very elderly patient in a
nursing home. The patient was quite demented, had very poor short-term
memory, and lacked decision-making capacity with regard to his own
medical care. The patient would periodically come up to the nursing
station at night saying he didn't feel right and needed a pill. New
staff came to the facility and noted that for a long time the patient
had been having this intermittent complaint at night, and had been given
vitamin C. The patient felt better and would go back to sleep. There
were a couple of things that came out of that discussion. One, there was
no specific symptom that could be found---he just said he didn't feel
right and wanted a pill---so there was really no other specific
treatment that could have been offered to that patient. Second, the
patient lacked capacity to even remember if he were told what he was
given was, in fact, vitamin C. Third, he had a surrogate who was told
ultimately that the patient was given vitamin C at night, and the
surrogate agreed to this treatment plan. I'm not sure that this is
actually an example of a use of a placebo.

**Joel Roselin, National Center for Ethics in Health Care:**

It seems to me that there can be a confusion between the sense of
placebo as a pill, which, in the past, you could even write a
prescription for all these different colors and sizes of pills, all of
which were inert, and the sense of placebo as when a physician writes a
prescription for a drug that the physician knows will not have any
effect on the patient's condition. It seems to me that the question of
the overuse of antibiotics can fall into this category. A patient
presents with a viral infection, and the physician gives them
antibiotics. All of their medical training tells them this is
inappropriate and won't help the viral infection, but, they think, it
won't hurt and it will make the patient feel better. Do you think this
falls into the category of placebo and poses similar ethical challenges?

**Lorraine Martin, VA New Jersey**:

I'm old enough to know what it was like to be giving placebo many years
back, and we did have positive reactions---pain relief, etc. In this
era, of course, the trend is toward patient participation, and I think
that is a very positive outcome. With the use of antibiotics for a viral
infection, I don't see that as a benign event, because people build up
resistance. But I really haven't seen the use of placebos for the past
ten years.

**Dr. Dastgeer:**

If a person comes and requests an antibiotic, we know it won't work, we
should be honest to say that the antibiotic won't work.

**Dr. Berkowitz:**

I think you're both saying the same thing---that it's not a good
practice to take the easy way out and prescribe a placebo or an
inappropriate medicine to a difficult patient. I never really thought of
that as a placebo, but it seems to fit.

**Brian, Battle Creek, MI:**

It's been several years, but we had a patient who, for whatever reason,
was not eligible to receive a nicotine patch to assist her in stopping
smoking. This patient then requested a placebo patch. Now, you've got
informed consent there because she understands that it's not going to do
anything, and she understood that, but that it would give her comfort
and support in her efforts to stop smoking.

**Dr. Berkowitz:**

And I think this case would actually fit the outline of what Tim
suggested a physician run through before giving a placebo. In this case
I think the patient's diagnosis is pretty firm---she wanted help to stop
smoking. There's no sense that it was being used as a diagnostic tool,
they were ineligible for other therapies, and there was no problem with
deception because it didn't entail denying the patient other therapies,
and there was valid informed consent. In this situation, I don't have a
problem with it.

**Brian:**

That was our thinking too, and I only brought that forward because of
all the comments that we should totally abolish this practice.

**Ellen Fox, MD, National Center for Ethics in Health Care:**

I remember vaguely reading an article 15 years ago testing the use of
placebo with informed consent. The patient was told that they were going
to be given a sugar pill, and that the sugar pill had no specific effect
on their symptoms, but 30% of patient's symptoms responded anyway, and
that this was a known psychological effect. Did you come across that in
your research?

**Dr. Berkowitz:**

We came across something similar to that. In the early nineties there
was an article published on a randomized trial on the analgesic activity
of placebo versus naprosyn in cancer pain. It's a little bit different
because it was a cross-over study. The patients were told that sometimes
they were going to be given a placebo, and at other times, a real drug.
The results of the study were that patients did have some symptom relief
with the placebo, but they reported more symptom relief with the real
drug.

**Dr. Fox**:

My recollection of the study is that it studied only placebo, and the
conclusion was that deception was not necessary for the placebo effect,
only that the patient believes that the physician believes that it might
help.

**Dr. Berkowitz**:

Which opens the question of whether the placebo effect comes from the
taking of the pill, or the interaction with the physician.

**Eric Undesser, Jackson VAMC**:

I've got another spin for you. A patient presents with a diagnostic
dilemma of seizures versus psuedo-seizures. The patient is taken to the
monitoring unit---the convulsions are tapered and nothing's happening,
and they inject saline with instructions to the patient that this may
precipitate a seizure to test whether the seizures are real.

**Dr. Berkowitz**:

This is clearly trying to use placebo as a diagnostic tool, which I
don't think we can support.

**Dr. Fox:**

In situations where there is some sort of psychological problem that
inhibits function, I was trained to use ritualized treatments. In other
words, you tell the patient, "I'm going to do this, and do that, and
that should make you feel better." And I've seen this work more than
once where the patient is "miraculously" cured. The patient isn't
thought to be faking, but somehow through this ritual, there is a
positive effect.

**Dr. Berkowitz**:

And the same could be said for patients with psuedo-seizures, because we
can't say with certainty that those are volitional.

**Peter Hauser, MD, Portland VAMC**:

Are you planning to have a discussion on placebo use in research?

**Dr. Berkowitz**:

I think that's a good topic for a future teleconference. In putting this
call together, we realized that putting both clinical and research use
of placebo in one call would be just too much.

**[FROM THE FIELD]{.smallcaps}**

Now I want to turn to our "From the Field" segment, where we take
comments from our listeners on ethics topics [not]{.underline} related
to today's call. Please remember, no specific consultation requests in
this open format, but I invite you now to make your comments on other
ethics-related topics, or to continue our discussion on the clinical use
of placebo

**CONCLUSION**

Well, as usual, we did not expect to conclude this discussion in the
time allotted, and unfortunately we are out of time for today\'s
discussion.

We will post on our Web site a very detailed summary of each National
Ethics Teleconference. So please visit our Web site to review today\'s
discussion. We will be sending a follow up email for this call that will
include the links to the appropriate web addresses for the call summary,
the CME credits, and the references referred to.

I would like to thank everyone who has worked hard on the development,
planning, and implementation of this call. It is never a trivial task
and I appreciate everyone\'s efforts, especially, Barbara Chanko,
Nichelle Cherry, and other members of the Ethics Center and EES staff
who support these calls.

-   **NEXT CALL**: Please remember that there will be no NET call in
    August. The next call in the series will be on Wednesday September
    29, 2004 from 1:00 to 2:00 Eastern Time. Please look to the website
    and to your Outlook email for details and announcements.

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-   Please let us know if you or someone you know should be receiving
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-   Please let us know if you have suggestions for topics for future
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Again, our e-mail address is:
[vhaethics@hq.med.va.gov](mailto:vhaethics@hq.med.va.gov?subject=National Ethics Teleconference).

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