The Placebo Effect

Recently the Federal Trade Commission went after the makers of the Q-Ray Ionized Bracelet for their claims that their device was a cure for chronic pain. Last week Seventh Circuit judge Frank Easterbrook handed down his opinion on the company’s appeal, writing that the company was guilty of fraud and ordering them to pay 16 million dollars in fines. One of the key points for the company’s defense was that the Q-Ray Ionized Bracelet is legit because it exhibits the placebo effect. Judge Easterbrook was not impressed with this argument, writing:

“Like a sugar pill it alleviates symptoms even though there is no apparent medical reason. Since the placebo effect can be obtained from sugar pills, charging $200 for a device that is represented as a miracle cure but works no better than a dummy pill is a form of fraud.”

This decision creates an interesting precedent, since there are a large number of fanciful treatments that do not have any “apparent medical” mechanism and that are claimed by its proponents to work through a placebo effect. In my experience the placebo effect, briefly defined as a measurable response to an inert treatment, is almost completely misunderstood by the public – a fact that is exploited by purveyors of dubious treatments such as the Q-ray. Already in the comments of this blog there has been discussion over the nature of the placebo effect.

In order to demystify the placebo effect, I will try to first describe exactly what it is. The operational definition of a placebo effect is any health effect measured after an intervention that is something other than a physiological response to a biologically active treatment. In clinical trials the placebo effect is any measured response in the group of study subjects that received an inert treatment, such as a sugar pill. However, “the placebo effect” is a misnomer and contributes to confusion, because it is not a single effect but the net result of many possible factors.

The various factors that contribute to a measured or perceived placebo effect vary depending upon the situation – what symptoms or outcomes are being observed. Subjective outcomes like pain, fatigue, and an overall sense of wellbeing, are subject to a host of psychological factors. For example, subjects in clinical studies want to get better, they want to believe they are on the active experimental treatment and that it works, they want to feel that the time and effort they have invested is worthwhile, and they want to make the researchers happy. In turn, the researchers want their treatment to work and want to see their patients get better. So there is often a large reporting bias. In other words, subjects are likely to convince themselves they feel better, and to report that they feel better, even if they don’t. Also, those conducting a trial will tend to make biased observations in favor of a positive effect.

It has also been clearly demonstrated that subjects who are being studied in a clinical trial objectively do better. This is because they are in a clinical trial – they are paying closer attention to their overall health, they are likely taking better care of themselves due to the constant reminder of their health and habits provided by the study visits and attention they are getting, they are being examined on a regular basis by a physician, and their overall compliance with treatment is likely to be higher. So basically, subjects in a trial take better care of themselves and get more medical attention than people not in trials. If for those not in a clinical trial, if they decide to do something about their health by starting a new treatment, they are likely to engage in more healthful behavior in other ways.

A common belief is that the placebo effect is largely a “mind-over-matter effect,” but this is a misconception. There is no compelling evidence that the mind can create healing simply through will or belief. However, mood and belief can have a significant effect on the subjective perception of pain. There is no method to directly measure pain as a phenomenon, and studies of pain are dependent upon the subjective report of subjects. There is therefore a large potential for perception and reporting bias in pain trials. But there are biological mechanisms by which mental processes can affect pain. There are many non-specific factors that can biochemically suppress pain. For example, increased physical activity can release endorphins that naturally inhibit pain. For these reasons the placebo effect for pain is typically high, around 30%.

But the more concrete and physiological the outcome, the smaller the placebo effect. Survival from serious forms of cancer, for example, has no demonstrable placebo effect. There is a “clinical trial effect,” as described above – being a subject in a trial tends to improve care and compliance, but no placebo effect beyond that. There is no compelling evidence that mood or thought alone can help fight off cancer or any similar disease.

Other conditions are more objective than pain, but are special because they have a strong influence from the neuro-endocrine system. This system translates psychological stress into physical stress, by releasing stress hormones and increasing activity in the sympathetic nervous system. So, for example, for heart disease mood matters quite a bit. Someone who has an A-type personality and is always angry and upset is at higher risk of a heart attack than someone who is mellow and unstressed. But here there is a known physiological connection between mood and a specific organ – the heart. This cannot be extrapolated to other diseases; it doesn’t mean you can smile your cancer away.

Many people talk about the neuroendocrine system’s effect on the immune system. Again, here there is a physiological connection. Stress hormones do suppress the immune system, and it is probably true that extreme stress leaves us physically susceptible to disease for this reason. But the effects of moderate levels of stress are not established. Also, we cannot extrapolate from the risk of getting a cold to the ability to fight off cancer. You have to look at the evidence for each disease unto itself. So while this is a potential contributor, it is overall probably a small effect except in extreme situations.

The lack of any real biological placebo effect has led some to question the necessity of having a placebo control in clinical trials. However, I feel there is still a need for a double-blind placebo-controlled design for most clinical trials because that is the only way to minimize the effects of bias on trial outcomes. The factors I listed above will still create the illusion of an effect and the only way to control for this is with a placebo group.

Therefore the placebo effect is fairly complex and is largely an artifact of observation and confounding factors. Any real benefits that contribute to the placebo effect can be gained by more straightforward methods – like healthy habits, compliance with treatment, and good health care. The placebo effect is not evidence for any mysterious mind-over-matter effect, but since the mind is matter (the brain) and is connected to the rest of the body, there are some known physiological effects that do play a role (although often greatly exaggerated).

In light of all this, I do not feel that knowingly prescribing a placebo treatment is effective or ethical medicine. Modern scientific medicine should strive for interventions that physiologically are scientifically plausible and have sufficient evidence for safety and effectiveness. But I do think there are lessons to be learned from the placebo effect – there are aspects of therapy that do go beyond the physiological intervention. Medicine is not only an applied science; it is the art of humans treating other humans. As part of effective treatment it is helpful to try to maximize all those human intangibles that contribute to a good outcome. But we can do this in the context of scientifically valid treatment, and without crossing the ethically dubious line of deception.

I therefore heartily agree with Judge Easterbrook that invoking the placebo effect is not a defense for making fraudulent health claims, for the Q-ray or any other implausible treatment.

Posted in: Clinical Trials, Science and Medicine

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25 thoughts on “The Placebo Effect

  1. PalMD says:

    I agree that it is ethically impermissible for doctors to prescribe placebos, as it involves actively deceiving a patient.

    It is *not* ethically unsound to “hype” a treatment, in that if a patient has confidence in a treatment they are more likely to be compliant, etc. For example, I often will tell a patient that the medical regimen for their heart disease will help prevent them from dying, etc (which is true), making them (I hope) more likely to stick to it. I work with residents every day, and many of them have not learned that yet (I’m working on it!).

    But creating confidence in a treatment/physician/relationship is not placebo—just good medicine.

  2. Apreche says:

    I also agree that it is unethical to prescribe placebos to people who have true illness. However, I am torn on whether it is ethical to prescribe them to hypochondriacs.

    If someone believes they are ill, when they are not, then perhaps a placebo is a good treatment as long as it is in combination with proper psychological treatment as well. One alternative seems to be to either give them a real treatment for a condition they only believe they have, which is clearly out of the question. The other option seems to be to just send them home telling them they are not ill. That option would seem to result in them turning to pseudoscience for help.

    I guess that just the psychological treatment alone would be ethically ideal, but since it won’t be effective immediately, it may still result in a turn towards fraudulent treatments.

    I’m a tech person, not a doctor, so obviously I have no clue what I’m talking about. I’d love to hear what experts have to say about this issue, and that is why I like this blog.

  3. daedalus2u says:

    As someone who has thought a great deal about the placebo effect in the context of my NO research I have a slightly different perspective. I would distinguish between non-physiological effects, such as investigator bias, and what I consider to be the “true” placebo effect mediated through physiology. I appreciate that this distinction may be difficult (if not impossible) to make experimentally unless specifically looked for (which most trials don’t). In the context of treatment the distinction doesn’t much matter. In the context of clinical trials it can. A single blinding (of patients) might work to correct for the physiological placebo effect mediated though patient physiology, investigator blinding is necessary to correct for investigator bias. In clinical trials double blinding corrects for both, which is why it is the gold standard for clinical trials.

    I completely agree that prescribing placebos has no place in any treatment modality. There are plenty of lifestyle changes that can be prescribed, diet, exercise, weight loss, stress relief that will do the same things and much more reliably than a placebo medication. Learning how to relax via the relaxation response

    invokes all of these same pathways (as I understand them), and again more reliably than any placebo.

    I know that my views of the mechanisms and magnitude of the physiological effects of the placebo effect are larger than what is considered “main stream”, however the most I see the placebo effect doing is restoring physiology to the “default” base-line state of normal health. I can think of no mechanism(s), by which the placebo effect would be effective at treating cancer, infections, trauma, or any disorder not caused by chronic stress. Even then it works as a preventative to prevent future damage, not to correct damage already done.

  4. BlazingDragon says:

    This discussion is interesting and touches on an issue I have strong feelings about. Is someone a hypochondriac or do they have a relatively rare disease (or a rare manifestation of a more common diseaese)? Too many physicians make the assumption, if simple lab tests do not show anything, that the patient is a hypochondriac. They prescribe therapies to get the patients to “shut up,” hoping the “placebo effect” will give the patients relief.

    This discussion about the placebo effect and how it is unethical to prescribe therapies mostly (or wholly) intended to get a patient to stop calling the doctor miss the fact that it happens often in real practice.

    Discussions like these are extremely frustrating to me because they talk about an idealized medicine standard that is rarely met these days in actual practice. The time/money constraints put on doctors render ideals pretty much moot for the general public that contacts the health care delivery system these days. I’m all for these discussions on how to make medicine better, but we also need to find ways to make these ideals a much larger part of everyday clinical practice.

    I firmly believe that clinical trials with double-blinded, placebo-controlled designs are the only validation for therapies. Just because someone “thinks” a therapy might be effective doesn’t make it so, even if the therapy is a new application for an approved drug (see the whole Zetia mess). But Apreche has a very relevant point about people turing to pseudo-science if they feel ignored by the “system.”

    I watch a lot of Discovery channel shows, so I saw this “ionizing bracelet” crap years ago and couldn’t believe they were selling it (it’s kind of sad how Discovery has to finance themselves with pseudo-science crap because “real” advertisers don’t advertise on “science” channels). I’m glad to see they got their come-uppance and the judge hit on exactly the reason why they are frauds.

    I wonder how long those japanese toxin-removing foot-pads I’ve seen lately on Discovery will be allowed to sell their crap before they are busted for pseudo-science too (they make even more radical and testable claims about being able to withdraw toxins and heavy metals by sleeping with their special pads stuck to the bottom of your feet).

  5. Calli Arcale says:

    I have a relative (now long since retired) who used to prescribe placebos for particularly troublesome patients whom he deemed to be hypochondriacs — only they weren’t just sugar pills, they actually were a drug that caused mild nausea. He would warn patients to expect mild nausea as evidence that it was working. They’d go away happy, then come back to report on how well the medicine had worked. When I was younger, I used to think that was a shrewd idea on his part. Now that I’m mature, I find myself wondering if this was part of the reason why he suddenly had to move his practice five hundred miles west (and into another state) just a few years shy of retirement.

    What he did was actually *worse* than mere deception, since evidently what he gave the patient actually did have an affect, and an unpleasant one at that.

  6. Roy Niles says:

    When you talk about treatment “without crossing the ethically dubious line of deception,” are you inferring that deception is ethically dubious per se, or that there is a line between acceptable and unacceptable forms of deception.
    I would presume you mean the latter, but even so, the standards for determining where that line is crossed might be a good subject for further discussion.

  7. psamathos says:

    Thanks for the interesting write-up. I also found Mark Crislip’s podcast about the placebo effect informative, if anyone else is looking for more information on misconceptions about the placebo effect:

  8. daedalus2u says:

    I think that any deception in any (purported) therapeutic setting is unethical. I actually think that deception in any setting where there is an expectation of trust is unethical and is a violation of any type of professional conduct.

  9. Roy Niles says:

    There are aspects of deception, both passive and active, that are considered ethical and moral, and that exist in different ways in every profession (and every culture for that matter). It may seem paradoxical, but trust depends on knowing those in that profession understand the difference, and apply that understanding in the best interests of their clients. Problems arise when the “cultural” standards of the particular profession are violated, ignored, twisted, subverted, and when there is no clear agreement as to what those standards should be, and no clear method of enforcing them.

  10. The question of deception, that I only touched upon in this entry, is a very interesting and important one so I think I will write a thorough treatment of it for my blog entry next week. Stay tuned.

  11. daedalus2u says:

    For me, my complete unwillingness to be deceptive relates to my knowledge that I do make mistakes. When I am in a position of trust, my mistakes can hurt people who are trusting me and who I don’t want to hurt. Being as truthful with those who are relying on me as I am with myself relieves me of (most) any guilt due to error.

  12. daedalus2u says:

    Another reason I don’t like to be deceptive is because the “best” way to lie is to also lie to yourself that is to believe the lie that you are telling. Figuring out physical reality is difficult enough as it is without injecting lies into it. One you start spreading lies, you start believing lies. When you believe in lies, even “harmless” ones, your conceptualization of reality breaks down and it becomes unreliable.

    In the context of administering placebos, if you started to do it and saw that they “worked”, it wouldn’t take much rationalization to ascribe mechanisms beyond that of the placebo effect. It is a slippery slope that could take you down into the abyss of quackery.

  13. Roy Niles says:

    As someone once said, one aspect of deception involves the process of persuading yourself you haven’t just engaged in self-deception.

  14. says:

    I think one of the best ways to start to understand the placebo effect is to speak with scientists who develop drugs or with the stock brokers who follow the industry. The scientists tell tales of experimenting for years on substances that they believed were going to cure horrible diseases only to find out as they tested further that they had been wrong.

    When you deal with an organism as complex as a living human being, there are many unknown variables which affect the course of a disease. The placebo effect is an umbrella term used to cover them all. While double-blind clinical trials will tell you if a drug is effective, they will not tell you what has caused significant improvement in any particular test subject receiving a placebo.

    In my experience it is very difficult for many people, especially many people in engineering and the “hard sciences” to accept and deal with the unknown variables in medicine. It is the reason that many are taken in by “alt med” and claims which may sound logical but which cannot be supported by evidence, such as the claim that a supplement that kills bacteria in vitro will also do that in vivo.

  15. overshoot says:
    “In my experience it is very difficult for many people, especially many people in engineering and the “hard sciences” to accept and deal with the unknown variables in medicine. It is the reason that many are taken in by “alt med” and claims which may sound logical but which cannot be supported by evidence, such as the claim that a supplement that kills bacteria in vitro will also do that in vivo.”

    I think that very much depends on the “hard science” in question. Certainly physics and electronics do so much in the realm of quantum mechanics that we have no excuse for not appreciating the chaotic nature of complex systems.

    As for the vitro/vivo issue, please correct me if I’m wrong but IIRC it’s pretty safe to say that an agent that is bactericidal in vitro _will_ also kill them in vivo; it’s just that you can crank up the concentrations in vitro to levels that would be unattainable or intolerable in vivo. My current favorite is the bunch pushing various forms of silver as a magical antibacterial. They promote low concentration systemic use while citing high concentration topical use to argue effectiveness.

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