Placebo 1 - the deceptive effect

Franz Messmer who operated in France at the end of the 18th century, claimed to be able to cure a host of diseases using Magnetized water, who work, according to him, on the "animal magnetism of the patients". The effects of the treatment were extremely dramatic. People even came to fainting as a reaction to those special waters.

But there were also skeptics. In 1785, Louis XVI convened a royal commission to examine the issue. The committee, which included Benjamin Franklin, conducted experiments in which one glass of "magnetized" water was placed between four identical glasses filled with normal water. Volunteers chose a cup at random and drank from it. There were still cases of fainting, but not exactly from drinking the magnetized water...

At the end of the experiment, the situation became clearer: No connection was found between the glass from which the volunteers drank and the symptoms that they developed or did not develop. The conclusion - the reactions resulted from the expectation only that something would happen, regardless of the type of water that was in the glass. Another conclusion was that Mesmer was a fraud. This was probably one of the first recorded clinical trials in history, in which the concept of blindness, that is, a situation in which the patients do not know whether they are receiving the expected treatment or a fake treatment. (Ironically, but predictably for those who have already followed the ways in which illusions spread, the "animal magnetism" movement not only did not wane but even strengthened thanks to the publicity she received following all the involvement in the issue).

A few years later, in 1796, a similar thing happened in America. The first US medical patent was granted to Elisha Perkins, who invented a pair of metal rods capable of drawing pain out of people. Tractors he called them ("Moshen").

It was enough to flutter the rods over the painful area for a few minutes for them to suck up the "harmful electric fluid that lies at the root of the pain". (In every era, fraudsters use concepts from the forefront of science to give their charlatanism a scientific face. In that era it was electricity. Nowadays, they use "quantum theory" or "chaos theory" for this purpose).

Perkins boasted thousands of satisfied patients, won the support of medical schools and interest from famous figures such as George Washington, for example, who purchased a pair of rods. Soon Perkins' son also joined the family business and both of them made a lot of money from providing treatments and selling rods at sky-high prices, prices which they justified by claiming that the rods were made of rare metal alloys that gave them their special healing powers.

But even here the skeptic finally arrived who decided to look into the issue. This time it was an English doctor named Haygarth (Haygarth), who made a pair of fake poles (made of wood coated with metallic paint) that are indistinguishable from the real ones. Four out of five subjects reported improvements in their health whether the real or fake rods were used.

Haygarth explained the surprising findings by saying that the strong effects of the rods on disease are created through imagination alone. That is, A patient's belief alone that he is receiving effective treatment can result in an improvement in his condition, or at least make him believe that his condition has been improved.

For example, when Haygarth treated a woman with a locked elbow with the fake rods, the woman claimed that her mobility improved. In fact her elbow remained locked, but she compensated for the limitation by increasing the rotation of her shoulder and wrist. We will return to this interesting point later.
The placebo effect It is the name given to the better feeling that a person gets as a result of a futile treatment that lacks any medical efficacy. The origin of the word placebo is in Latin, and it means "I Shall Please".

Haygarth realized a few other important things. He realized that the placebo effect actually enhances effective treatments, and asked himself how the effect could be increased even more. Since the effect was due to his opinion From the trust that the patient acquires in the treatment and the therapist, he concluded that the higher the reputation of the doctor, the cost of the treatment and the degree of innovation, the greater the placebo effect. Another 200 years passed before these hypotheses were scientifically proven.

We skip forward about 150 years, to another famous researcher of the placebo effect: the American Henry Beecher (Henry Beecher). His interest in the subject began during the Second World War, against a background of severe distress in the means to properly treat the war wounded. When the supply of morphine ran out, Beecher decided to conduct a daring experiment. He injected the wounded man with saline but told the wounded man that it was a strong pain reliever. to his surprise The injured man calmed down immediately and showed no signs of pain. The miracle happened again and again with many other injured people!
After the war, Beecher laid the foundations for organized research in the field.

The effectiveness of a new treatment
We will use the opportunity to stop for a moment and think - how do we know if medical treatment is effective? (This can be medication, physical therapy, surgery, etc.).

Let's say that Liusi has a headache. Yossi swallows an experimental medicine against headaches and indeed the next day the pain is gone. Is the drug effective? Naomi, on the other hand, swallowed the medicine, and her headache only got worse, but it went away two days later. Is the medicine ineffective?

It is difficult to learn something from two cases. It is possible that other factors are not related to the treatment at all they who were responsible for the change in the situation. In order to offset the influence of such and other unknown factors, the treatment must be checked Multiple as many people as possible.

Let's say that 100 people received the experimental drug, and 50 of them improved significantly within two days. Is the treatment successful?

There is no way to determine this of course, if not Compare the results to a group of other people who suffered from the same problem but did not receive the treatment. If the number of healers is significantly large among the group receiving the treatment, it can be said that it is effective.

But in light of the cases we described earlier, it is clear that there is a big problem in evaluating the effectiveness of the treatment, since it is possible that the condition of the patients has improved Not as a result of the specific treatment, but only out of the expectation that their condition will improve! How can we distinguish between the two?
Those historical pioneers that we met earlier actually found the solution to the issue: it is necessary to ensure that the patients do not know whether they are receiving treatment or not. The experimental group is given the real treatment and the control group is given Sham treatment, in such a way that the subjects do not know which of them receives what. That way, everyone's expectation will be the same, and this factor will be removed from the comparison. If a distinct advantage is found for those who received the real treatment, then it has an added value beyond the placebo effect. If the results in both groups are the same (as good as they will be), then the treatment has no real medical benefit in itself.

If the real treatment is the administration of a certain pill, the dummy treatment will be a pill that looks exactly the same even contains no active ingredient. If the treatment is an injection of a certain substance, the sham treatment will be an injection without an active substance, etc.

From the patient's point of view There must not be any difference between the real treatment and the sham treatment, so that there is no difference in expectations. The treatment should take place in the same place, by the same therapists, the patients should receive the same explanations, the same treatment, and the results should be monitored with the same frequency and in exactly the same way. Such an experimental method is called The blinding method (Blind).

But it turned out that not only the patient affects the placebo effect, The therapist too related to the effect. If the therapist Knows which of the patients is receiving real treatment and which is not, he may pass this information on to the patient unconsciously. Something in the tone of voice may be different, in the length of the explanations, in relation.
An instructive example of indirect influence of the researcher can be found In the next study, who examined patients suffering from postoperative pain. The patients were divided into two groups. to the patients Both groups were told the same thing - they would receive either a placebo or a real painkiller.
to caregivers In contrast, subjects in one group were said to receive only a placebo, while some subjects from the other group would receive a real pain reliever.
In practice, the placebo effect was much smaller in the group about which they believed the caregivers Because there is no chance that its patients will receive a real pain reliever. All this without an exchange of words between the therapists and the patients!
Therefore the accepted protocol is double-blind in it Neither the therapist nor the patient Know who gets real treatment and who gets fake treatment.
This is the highest standard today for clinical trials in new treatments: A large group (thousands of subjects), randomly divided into two groups - an experimental group (receiving the real treatment) and a control group (receiving a sham treatment). The distribution is done double blind (no one knows who is in which group).
In addition, it is desirable that those who analyze the results of the experiment do not know who received a real treatment and who received a sham. Such a situation is called triple-blindness (Triple blind). Such a protocol cleans up all the biases we mentioned.
[An example of embarrassing results reached by researchers (real or simulated) when they do not use double and triple blinding protocols we met here for example – “What for all the blip are they talking about?! – The Japanese and his ice crystals"].

The amazing power of the placebo
In 1955, Beecher published the founding and most cited article in the field - "The Powerful Placebo", in which he reviewed 15 clinical trials and found that the condition of about a third Out of over 1000 subjects, the placebo treatment alone improved.
Over decades of clinical trials of new drugs, the phenomenon repeated again and again: tens of percent of the group receiving the dummy drug reported an improvement in their condition. Some of them even developed side effects attributed to the drug!
Furthermore, there are recorded cases in which people opened Withdrawal difficulties with cessation of placebo treatment. for example, In an experiment in which hormonal treatment was given to women and tested the effect of stopping it, it was found that 40% of women from the control group who received a placebo Suffer from side effects!

As good as placebo? Disqualified!

And here comes a strict guiding rule in the process of developing a new drug: If no clear and significant advantage is found for the experimental group over the control group (placebo recipients), the treatment is declared a failure and its development process is stopped. Years of clinical trials and tens of millions of dollars go down the drain. Examples are not lacking:

• Shares of a company that developed an anti-allergy drug (Peptide Therapeutics) fell by 33% after it became clear that the drug is no more effective than a placebo: during the experiments on subjects who were allergic to a certain food, 75% reached a situation where they overcome the side effects of eating food that they were never able to eat. The surprise came when it turned out that 75% of the subjects in the control group also benefited from the same improvement!
• The pharmaceutical company Merck announced the cessation of development of an anti-depressant drug (MK-869) that was expected to have similar success to Prozac, since the placebo worked just as well.

Depressing facts about antidepressants?

Super review From 1998, trials of antidepressants found that 75% of their effectiveness can be attributed to the placebo effect and other general factors rather than to the treatment itself. Another review which also included unpublished experiments (probably those whose results were less favorable, but their inclusion gives a truer picture of the situation of course), found that There is no significant difference between the drugs and the placebo, except in extreme cases of severe depression. Additionally, no significant difference was found between the rates of suicide or suicide attempts between those taking antidepressants and those taking placebo.
Here is a quote from Washington Post article from 2002: "In most of the experiments conducted by the pharmaceutical companies in the last decades, the performance of sugar pills [synonymous with placebo] did not fall, and even rose on the performance of antidepressants. Companies had to make many attempts just to get two trials that show positive results of the drugs - the minimum required by the FDA in order to approve a drug. The manufacturer of Prozac needed 5 trials to get 2 positive results, and the manufacturer of Paxil and Zoloft needed even more."

Before we look at the article on the subject, I will point out that this information is controversial.

Placebo is not only in medicine. Even in surgeries!

Over the years, more and more evidence has been accumulated of the effect of the patient's faith on his feelings, even when he was not given any real treatment. Here are some famous examples:

Internal thoracic artery ligation surgery - In the middle of the 20th century, it was customary to treat cases of angina (which manifests itself in chest pain) by an operation in which one of the arteries was tied. The assumption was that the ligature would raise the blood pressure in the coronary arteries, and improve blood flow and oxygen supply to the heart muscle. According to the testimony of the patients, the operation provided relief for several months.

In 1955, a cardiologist named Cobb suspected the effectiveness of the treatment, since post-mortem examinations of patients showed no sign of improvement in flow. Cobb performed a placebo-controlled trial: in half of the patients he performed the usual surgery, and in the other half he only performed an incision, No Tie off the artery, and sew it back up. The results were the same! Most patients From two The groups reported a significant relief that lasted about 3 months, then the situation returned to normal. There was no meaning in tying the artery!

Knee surgeries to remove damaged cartilage - In the mid-90s, an orthopedic surgeon suspected the effectiveness of a certain type of knee surgery that was practiced mainly among athletes. Hundreds of thousands of such surgeries were performed each year, at a cost of thousands of dollars per surgery. It was known that the condition of About half Of those who were operated on, it was getting better, but it was not clear what the mechanism of the improvement was. in the research that was carried out To test the issue, 180 patients with osteoarthritis were divided into three groups who received the following treatments:

• Group A - full treatment: 3 incisions, removal of cartilage and rinsing with salt water.
• Group B - partial treatment: 3 incisions and rinsing with salt water.
• Group C - placebo: 3 incisions only, without any additional activity.

The members of groups A and B were very satisfied with the treatment, felt a significant improvement in walking ability and said that they would recommend the surgery to their friends. Surprisingly, the improvement in the condition of group C berries was the same!

You can see a video about the experiment here.
It seems that the reality of the placebo exceeds all imagination!
But let's not rush. In the next post What we have learned about the placebo effect is about to undergo a significant upheaval...