Is the placebo effect in medicine a fiction?

A "Golem" is a human puppet in Jewish mythology made of clay, water, and charms, unaware of either its own power or its own clumsiness and ignorance. Medicine is also a "Golem," a complex creation with uncertainty. In "Dr. Gollum: How to Understand Medicine," the author takes eight topics from the socialization of modern medicine to analyze them in depth, trying to loosen the cognitive "sand" and "knot" of modern medicine, clear up its modernity myths, and understand how medical knowledge is constructed and understood through The book also attempts to clarify the myths of modernity, and to carefully sort out the key conflicts in how medical knowledge is constructed and used. This article is an excerpt from the first chapter of the book, "A Major Conundrum in Medicine - The Placebo Effect.

The placebo effect has been an integral part of modern medical science since at least the 1950s. Studies have shown that 20 to 70 percent of patients seem to benefit from placebo treatment. Perhaps the most dramatic is placebo surgery, in which a patient is properly anesthetized and then only an incision is made in the patient's skin, without any substantial surgical intervention on the patient. This placebo surgery has been reported to be very effective. Indeed, sometimes simulated surgery seems to be more effective than real surgery. For example, in the treatment of certain heart pain and back pain, such surgery can be useful, and in the mid-1990s, research found that simulated surgery could treat knee osteoarthritis. In the treatment of this disease, internal knee cleanings were considered the standard of care for high efficiency, but patients who were simply cut through the skin of the knee healed just as well as those who had internal knee cleanings.

Unfortunately, these seemingly clear-cut findings are actually questionable. Now we have to traverse an even more dizzying hall of mirrors: patients are able to recover even without any treatment, and those who are given placebo treatment and those who receive full medical intervention may heal on their own at the same rate. In other words, those patients who took placebos and received placebo therapy may not have been made well by the placebo effect, but healed on their own. At the same time, patients who underwent major surgical procedures also healed on their own because medical treatments were equally "ineffective" for them. In this case, rather than saying that the placebo effect is as effective as real surgery, the placebo effect is as ineffective as real surgery.

In order to investigate whether the placebo effect really exists, we must do another kind of experiment. In this experiment, we must compare the condition of the group of patients who received a placebo with the group of patients who did not receive any treatment. In this case, the existence of the placebo effect can be proven only if the group of patients who received the placebo recovered better than the group of patients who did not receive any treatment.

In 2001, two Danish physicians, Hrobjartsson and Gotzsche, analyzed all the articles they could find comparing the condition of patients who did not receive any treatment with those who received a placebo. Of the 114 trials reviewed by physicians mentioned in these articles, only a few were designed to directly detect a placebo effect. Most of the trials conducted subjects in three groups: a group of patients who received medical therapy, a group of patients who received placebo, and a group of patients who did not receive any therapy. They found essentially no difference in patient improvement between patients receiving placebo and those who did not receive any treatment.

This seems like a pretty definitive conclusion, and at first glance, the study by the two Danish doctors is quite convincing. They analyzed a large number of studies, involving a large number of patients. Their findings seem to disprove many conventional views. However, a closer look at the carefully worded discussion at the end of the article reveals that this conclusion is flawed.

First, in the placebo effect test, there were data suggesting that the placebo gave the subjects some relief from pain; and there is also the possibility of more effective pain relief for a small number of patients or diseases, although not for all patients. The small size and number of cases of these adverse effects are easily masked by the cumulative statistical approach used by the two Danish researchers. More worrisome is the more complex logic described below, the complexity of which we have to emphasize by using an increasing number of exclamation points at the end of the sentences.

A test comparing a treatment, whether given as a placebo or otherwise, with no treatment given to a patient cannot be done in a "double-blind" situation! The patient and the physician treating the patient will know who did not receive the treatment. The fact that the patient is not receiving treatment cannot be concealed, otherwise it would not be "not receiving treatment", but essentially receiving a placebo treatment.

Now it gets complicated: if doctors and patients know who is not receiving treatment, there will be an expectation effect and a reporting effect, making the difference between a patient receiving a placebo and a patient not receiving any treatment more pronounced than the placebo effect would have made! In other words, patients who did not receive any treatment would be pessimistic about their condition, and those physicians treating them would have no expectation that this group of patients would get better. This would result in a stronger reporting effect from both physicians and patients, and the expectation effect would enhance this reporting effect. In summary, the crucial point is that even if no placebo effect is produced, these unblinded controlled experiments should appear to show a placebo effect due to the presence of negative reporting and expectation effects from the group of patients who did not receive any treatment. In an Alice in Wonderland-like world, such experiments should not be able to fail! Whether or not the placebo effect is real in these experiments, it should at least appear to be there!

Since there is no apparent placebo effect in these experiments, there can't be any expectation effect or reporting effect, but that would suggest that there is something wrong with the experiment itself! Just like Mendel's famous pea genetics experiment, the conclusion of the experiment was so perfect, too perfect to be true.

The two Danish authors countered that because most experiments have three groups instead of two, neither the patients nor the experimental analysts would focus on the difference between the group of patients treated with a placebo and the group of patients who did not receive any treatment, which could reduce the reported and expected effects. But this argument does not seem very convincing.

Even if the presence or absence of expectation and report effects were not decisive, there would still be another argument against questioning the conclusions of the experiment anyway. As we have said, patients who do not receive any treatment will inevitably know that they are not receiving any treatment. If the condition is severe, they may make the decision that since they did not receive any treatment in the experiment, they should treat themselves in a way that is not relevant to the experiment. Patients who received the placebo treatment would not have made this decision because they believed they were receiving treatment. The difference in the way these two groups of patients treated themselves may have led to no difference in the success rate of physical improvement between the two groups.

As is the case in most complex statistical sciences, the combined consideration of the two rebuttals to the findings of the two Danish physicians leaves us at a loss. All we know is that we cannot assume, as we have in the past, that a placebo effect does exist, but we are far from certain that it does not. What we need to do to resolve this is to conduct a double-blind trial on the group of patients who received the placebo treatment and the group of patients who did not receive any treatment - but strictly speaking, we can't do that! (Again, we have to put an exclamation point at the end of the sentence.)

Regardless of the academic debate, the placebo effect is treated as real by the pharmaceutical companies, the executive agencies of the clinical trials conducted by the pharmaceutical companies, and the critics of the pharmaceutical companies. Critics point out that the so-called double-blind method does not work because patients are often able to guess whether they are taking a real drug or a placebo by determining whether they will experience adverse effects such as dizziness or dry mouth after taking the drug. So this means that in a randomized controlled trial of a drug and a placebo, even if the drug group wins, it may only be because the drug with the adverse reaction produced a stronger placebo effect!

Pharmaceutical companies and the institutions for which they perform trials believe that the placebo effect is real, so they estimate the extent to which the patients they recruit are affected by the placebo and then try to avoid enrolling patients who are sensitive to suggestion (covert psychotherapy) and similar types of patients in the trial. At this point, on the question of whether the placebo effect exists, we can say this: in terms of its effect on our perceptions about medicine, the placebo effect is real.

Let's look at trials that test drugs or treatments that have long been thought to be effective, such as hormone replacement therapy (HRT for short). Now that there are hypothetical questions about the safety of hormone replacement therapy, it is agreed that it should be tested again using a new double-blind controlled trial. In this trial, patients would have good reason to believe that the drug would be physiologically effective, whether they were in the treatment group or the placebo control group. This situation would most likely lead to a very strong placebo effect because patients would have a high expectation of their recovery, i.e., if they are taking the real drug, then they should have significant efficacy. In conclusion, the strength of the placebo effect is influenced to some extent by the patient's trust in the efficacy of the drug, which in turn is based on the long-term experience of other patients taking this drug. Thus, if the trial proves that there is no difference between the placebo and treatment groups, this may not be because the real drug is not efficacious, but rather that patients taking the placebo have a strong expectation effect on the efficacy of the real drug. In these cases, any conclusion drawn from a negative result is likely to be incorrect.

The placebo effect clearly reveals the uncertainty that exists in modern medicine. But it also raises a perplexing question: If placebos really work, why are they not used systematically?

One of the answers is obvious. Suppose you ask a patient, "Would you prefer a real treatment or a placebo treatment?" Of course the patient would say, "I want the real treatment." Because, once you tell the patient it's a placebo, it doesn't produce the effect that a placebo is supposed to achieve, but rather amounts to no treatment at all. Any attempt to give the patient a choice will be botched. (This statement is a logical addition to the previous point: if you can convince a patient that not giving a treatment is itself a treatment, then the patient is not receiving no treatment, but rather the equivalent of receiving a placebo treatment!) In fact, doctors may - and do - manage to kindly withhold placebo treatment from their patients as long as they do not inform them of the true situation. A good doctor who wishes to give help to a patient when there is no scientific way to alleviate the condition should withhold the truth from the patient and offer the patient placebo therapy. But this placebo therapy can only work for patients who are unable to make a truly informed and autonomous choice, and the doctor cannot ask the patient, "Do you want to receive this placebo therapy?" Doctors have to hide this deception from their patients, and this deception does not qualify as giving them a real choice. The same is true of any institution that is responsible for the collective health of the general public. While placebo therapy is a useful and important component of existing medical treatments, you can't ask people to favor "more placebos in medical treatment. Can you do that?

Translated with www.DeepL.com/Translator (free version)