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The Placebo Effect–Myth vs. Science


Background

There has been a large uptick in interest about the so-called placebo effect, mostly from the complementary and alternative junk medicine (CAM) crowd. Evidently, they feel that being equivalent to doing nothing is good enough to be real. A recent article in the Wall Street JournalWhy Placebos Work Wonders, is indicative of this recent pro-placebo point-of-view.  

What exactly is the placebo effect? The definition is often misused, implying some beneficial effect from a sugar pill or sham treatment. But in medicine, a placebo is actually a failure. If a new pharmaceutical, procedure or medical device shows no difference in efficacy compared to a placebo, then it is rejected.  But the CAM-pushing herd thinks that proves its a success when one of its potions and lotions is equivalent to a placebo. What? A failure of a modality in evidence-based medicine is somehow converted into a successful product in the CAM world?

Myth

In the article, The Placebo Myth by Mark Crislip (an infectious disease specialist), Crislip questions the placebo effect, by asking, “why would actively doing nothing have any measurable physiologic effect? It shouldn’t and it doesn’t. Mind over matter? Bah, humbug.” He then continues, “I think that the placebo effect with pain is a mild example of cognitive behavioral therapy; the pain stays the same, it is the emotional response that is altered.” So, it’s therapy (albeit not very focused), not a sugar pill that works.

Richard Schiffman wrote How the Placebo Effect Proves That God Exists in the Huffington Post, which is considered one of the 10 most anti-science websites, so it’s hard to to take it too seriously. HuffPo, as it is known, sits amongst 9/11 denialists, the Australian Vaccine Network, and Answers in Genesis along with many others at the bottom of the internet’s anti-science dreck. Nevertheless, Schiffman argues that because we don’t know what causes the placebo effect, it is a proof of some deity. Wait, just because we don’t know what causes it, we then leap to that conclusion, an argument from ignorance, that we infer that a proposition is true (some deity)  from the fact that it is not known to be false. 

At any rate, Shiffman’s article is mostly a confusing discussion of trying to prove god exists, then makes this statement:

Which brings us back to the placebo effect. It is mysterious, right? We don’t know how it happens. A person was sick and they take a sugar pill and next thing you know — voila — they are healthy. To call this “the placebo effect” is to dress up our ignorance in words. What has actually happened is nothing short of a miracle. Science has got no explanation for it– something immaterial (a thought?) has impacted something material (our body) in a way which utterly defies logic.

And that is what prayer is all about. Prayer is based upon the conviction that the immaterial is more powerful than matter itself. Whether we call this immaterial force “God,” “the ground of our being,” “Spirit,” or “higher consciousness” doesn’t matter. The point is– there is an uncanny power (which all of us without exception have got access to) which performs miracles. The sick can be cured, the broken can feel whole again.

Wait, but we don’t have any evidence that the placebo effect exists. And science can explain almost everything about the placebo effect. This is not a proof of anything, let alone the existence of deities of any sort. In fact, show me the data. A person may be sick, takes a sugar pill, and “voila”, they are healthy, because the virus has run its course. Or a disease has gone into remission not because of the placebo, but because of some other physiological effect that has not been described. Just because we have not found the answer, does not mean we just invent an answer. Or just becomes something happens after we take a placebo, the post hoc effect, doesn’t mean we can attribute it to the placebo. 

Science

Back to Crislip’s article, he also discusses some some acupuncture studies where the treatment is compared to placebo (usually a sham procedure that feels like acupuncture, but no skin penetration occurs).  It was amusing that in some cases the sham was worse than the placebo, because the explanation of possible side effects of the procedures was enough to cause the cognitive behavioral therapy (or, participant effect in an experimental world).

He then tried to find placebo “effects” in veterinary studies (because we can assume that animals are resistant to cognitive therapy).  He concludes, “I tried other combinations of search terms using placebo and animals and could not find well done blinded studies that demonstrate any placebo effect in animals.”  This lead him to conclude that the “placebo effect is a myth: for humans and for animals.”  Remember, a placebo, in the medical/scientific world, is a failure, and if it doesn’t even have an “effect” it’s a serious failure.

If there is placebo effect, what exactly causes it? Is there a plausible, scientifically-based mechanism?
  • Expectancy and conditioning. There is a hypothesis that the placebo effect is related to the perceptions and expectations of the patient and the healthcare professional. If the drug or treatment is viewed as helpful, it can heal, but, if it is viewed as harmful, it can cause negative effects. Expectancy and condition contribute differently to the effect, with conditioning giving a more long lasting placebo effect
  • The brain. Functional imaging studies using placebo analgesia shows strong evidence that links the placebo to the activation, and increased functional correlation between this activation, to various brain activity (anterior cingulateprefrontalorbitofrontal and insularcortices, nucleus accumbensamygdala, the brainstem periaqueductal gray matter) and the spinal cord. But, as the authors state in their conclusion, “there are factors related to a clinical interaction that may produce improvement in patient outcomes without directly affecting the underlying pathophysiology of a disease.” Nevertheless, the placebo effect may produce an effect in the brain that controls some subcortical activity, which could have temporary, subclinical benefit in a number of analgesic and, possible, non-analgesic, conditions.
  • The brain’s control over other body functions. The brain has direct control over physiological functions like fever, pain, and motor fatigue. It also has some indirect control over some functions like the immune system, and some researchers have proposed that placebos can have beneficial effect on the immune system. But that’s it. No further data. No clinical trials. And lots of bias.

But, can it be described in other terms? That’s the problem. Summarizing an article by David Gorski at Science Based Medicine, 

  • It can be just a random statistical variability, and if the study is repeated 100 times, it may disappear altogether.
  • It’s almost always a subjective effect, meaning that it’s not a condition where the researcher can actually measure the effect in a laboratory test.  If we find a drug that actually eliminates HIV from the body, we can measure that.  But most studies that measure a placebo effect in a CAM treatment, it’s some measurement that’s hard to quantify.  Less pain is a usual one.
  • The subjectiveness then leads to some induced bias into the study, including the observer-expectancy effect ,where the researcher’s bias influences the participants or even that the participant expects to feel better; experimental bias where the actual design of the experiment leads to a positive result; or the Hawthorne effect, where the participant modifies their behavior just because they are being observed.
  • Maybe there is some “mind over body” effect, but there are no known mechanisms for this kind of effect.  And to dispel the old logical fallacy of “the absence of evidence is not evidence of absence,” we have looked for a mind over body effect, but have not actually found one. That is, in fact, evidence of absence.  But as a real scientist, it is important to note that many of us will jump on board if a mechanism is found, but the only ones I’ve read, energy fields, or some mysterious compound in the blood, stand in firm opposition to the basic laws of physics and chemistry.  In other words, there better be some good evidence for such a mechanism, and there is none.

What the Skeptical Raptor says

My issue remains that there just is no evidence that the placebo effect has any effect in real pathologies.  It cannot shrink tumors.  Oh sure, there might be some tumors that do shrink miraculously, but instead of assuming some magical response, I’m going to assume it’s not a miracle, but we just haven’t figured it out yet.  Yes, a good skeptic’s default position shouldn’t be “it’s a mystery we’ll never understand;” actually, it should be “it’s a mystery, let’s use science to understand it, because if we do, maybe we can cure everyone who has this disease.”  This isn’t an opinion, but the Cochrane Reviews (a group that does meta analyses of medical and scientific studies) made these comments in a review of placebo effects:

Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published.We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.

Simply put, there really are no placebo effects, except in patient reported outcomes, which are subject to all the biases I mentioned above. As David Gorski stated in his article about the placebo effect,

Placebo effects, more than anything else, appear to involve changes in how pain or subjective symptoms are perceived, not any physiological change that concretely affects the course of a disease. Consistent with this concept, I have yet to come across a study that provides serious objective evidence that placebos change “hard” objective outcomes, such as survival in cancer.

This is the most important point. Maybe there’s some evidence on a placebo effect on pain, which can be a subjective matter from person to person. But outside of that, the evidence becomes weak and even non-existent for serious diseases. There is no evidence that it can change the course of a chronic disease like cancer. Some claims have been made that a placebo effect can manifest a change in the immune system, but there is just no clinical evidence supporting that.

The placebo effect only exists in totally subjective environments. It doesn’t result from some mysterious (and improbable) mechanism. It isn’t a miracle. It is merely thinking you have less pain, because you’re told you should have less pain. But it doesn’t cure cancer or even a common cold. In fact, a lot of alternative remedies make cold and flu claims simply because colds and flus do disappear eventually, not as a result of any therapeutic cause, and certainly not because of placebos.

Is the placebo effect a myth? It’s a close call. Mark Crislip has me convinced, by a 51-49 vote, if you’re counting. If it weren’t for the pain effect, that is influenced by everything from how the physician treats a patient, to the wording of the informed consent, it wouldn’t be that close.  There’s not a lot of good clinical data, and what’s out there is subject to some negative interpretation. Maybe if there’s some better evidence in support of a strong placebo effect of “mind over matter”, I’d be convinced. But not right now. It’s a myth.

Michael Simpson

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