The placebo effect used to be seen as an interesting, minor side-topic of medical science. It was trivial conversation topic similar to superstitious beliefs like folk medicine and haunted buildings, but it didn’t need to be taken seriously as a real factor in medical treatments. This is no longer true. The placebo effect is now a very important issue in medical treatment and medical research.
Numerous studies have produced empirical evidence that proves the physiological effect of emotions on the immune system, the endocrine system, and on the occurrence of cancer and other chronic illnesses. Patients’ psychological state, their history of trauma—especially in childhood—and their beliefs and feelings can have a strong influence on their health and on the effectiveness of treatments they receive.
Placebos have also become a very important tool in medical research. The double blind, controlled, randomized study is considered to be the gold standard of medical research. No one takes seriously any research project that did not use a randomized control group given a placebo, even though there are other kinds of studies that are valuable in certain situations. Double blind studies also have to take account of the placebo effect on the group that was given the treatment being studied. If, for example, 25% of the subjects in the placebo group improved, or recovered naturally, it is likely that these same effects existed in the group that was given the treatment. The improvement in that group would have to be significantly higher than 25% for the treatment to be considered useful.
The alternative to the randomized study is the observational study. Observational studies are valuable in certain situations when it is not possible to carry out a randomized, controlled double blind study. In an observational study, researchers simply give a treatment to a group of patients and observe the results. The perceived values of observational and controlled studies were revealed during the coronavirus pandemic of 2020. In February and March of that year, one of the world’s leading virologists, French scientist Didier Raoult, used a treatment protocol using hydroxychloroquine (an anti-malaria medication) and azithromycin (an antibiotic) at a hospital in Marseille, France. He cited existing research that showed these drugs had been effective in treating other coronaviruses.
Dr. Raoult treated 1,000 patients with his protocol, and he reported that only one person died, a person who was elderly and would not have lived much longer in any case because he had other serious medical conditions. He also referred to doctors who were observing similar results throughout the world.(1) This result seemed like something the entire world would celebrate because the fatality rate was much lower than anywhere else, but instead, Dr. Raoult was severely criticized for spreading “false hope.” His critics said his conclusions were based only on an observational study. They wanted to see evidence from a randomized, controlled study using a group that received a placebo. Dr. Raoult protested that this was an absurd demand. It would be unethical to ask people to be in the placebo group in this case because it was a matter of people who were infected with a new sort of virus that could kill them within two weeks. No one would agree to be in the control group, and no doctor could ask people to volunteer to risk death.
The critics of Dr. Raoult protested further. They said hydroxychloroquine could cause a fatal heart attack in some patients. Dr. Raoult countered that such patients can easily be identified and excluded from the treatment. Next, these critics tested hydroxychloroquine in their own studies and they found it had no effect. Dr. Raoult pointed out that they had not followed his treatment protocol correctly. By doing so, it seemed like they were deliberately trying to show that it would fail. Two months later, the leading medical journal, The Lancet, published a controlled study claiming to show that hydroxychloroquine was ineffective, but two weeks after publication it had been criticized so much that the authors insisted that The Lancet retract it.(2)
Dr. Raoult continued to point out that many of the people trying to prove him wrong deliberately did not follow his protocol correctly. They gave the drug without azithromycin, or they gave it too late in the progression of the infection. Dr. Raoult stressed that high-risk patients had to be identified quickly and started on treatment as soon as they showed symptoms, before their blood oxygen levels fell below 95 or 90. He also stressed the drug’s value as a prophylactic—that is, people could take small doses before they became infected and it would prevent the corona virus from causing severe symptoms. In many African countries the corona virus never became a serious problem, and the reason might have been that people there regularly take hydroxychloroquine to prevent malaria.
Dr. Raoult became a prominent figure in the French mass media during this controversy. He had millions of supporters, and millions of detractors. He claimed that there was an unexplained campaign against his treatment protocol, and he questioned whether it was motivated by pharmaceutical companies that wanted to get approval for their expensive new drugs. He wondered why there was suddenly such a strong interest in rejecting hydroxychloroquine—a cheap and widely available drug that has been used safely for over a century. Knowing the powerful influence of emotions on the immune system, he also denounced the government’s and the media’s strange preference for generating mass fear. If critics were so motivated to say that natural recovery or the placebo effect explains the apparent success of treatment with hydroxychloroquine, why didn’t they worry more about the nocebo effect—the negative version of the placebo effect—in all the panic and fear that had been generated? He stated that this creation of fear was the most unforgivable thing about the reaction to the corona virus pandemic because it was certainly responsible for many of the illnesses and deaths.
During this time, US president Donald Trump spoke favorably about hydroxychloroquine, saying it seemed promising. Because President Trump is hated by half the world, anything he says is also hated and viewed as “fake news”. Dr. Raoult’s treatment protocol had now become a political issue, so it became even more difficult for Dr. Raoult to convince people to look at the established facts in research done before 2020.
For a while, some leading media channels showed support for Dr. Raoult and his treatment protocol. A typical example was Newsweek. It published a supportive editorial by epidemiologist Harvey A. Risch in July, 2020.(3) However, one month later, Newsweek published another editorial, authored by several doctors, that rejected the opinion in Dr. Risch’s editorial.(4) Since then, the mass media has stopped talking about hydroxychloroquine, as if the matter has been settled forevermore.
Interestingly, the demand for double blind and duplicated research didn’t apply to the policy of forcing citizens to wear surgical masks outside their homes. In many Asian countries, citizens are accustomed to wearing masks, but in Europe and North America, many people were angry about being forced to wear them and they were not convinced that the research confirmed the value of everyone wearing masks. Many doctors insisted that the masks were unnecessary and could have harmful effects, especially on children. They stated that the disease was spread mostly by hand-to mouth-contact, so it was more important to emphasize handwashing and cleaning of clothes and the rooms where people spend time. Nonetheless, governments around the world enforced mask wearing and started to apply criminal penalties to citizens who did not comply. The evidence they relied on was a study published in The Lancet (5) in which the authors admitted that there was no control group and that the study was an observational study testing a theory about mask-wearing in large populations being an effective way to reduce the spread of the Sars-Cov-2 virus.
It is curious that in this case an observational study was considered good enough, but in the attack on Dr. Raoult his work was dismissed for being “just an observational study.” Supporters of Dr. Raoult have stated coldly that his critics should fear the judgment of history. If his treatment protocol is proven effective, those who stopped its use will be guilty of having withheld life-saving medicine to millions of people.
(1) “Covid-19: Why treatment with chloroquine is being sabotaged,” Les Blogs de Mediapart, April 10, 2020. English translation here: https://dennisriches.wordpress.com/2020/04/16/1053/.
(2) Mandeep R. Mehra et al, “Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis,” The Lancet, June 13, 2020.
(3) Harvey A. Risch, “The Key to Defeating COVID-19 Already Exists. We Need to Start Using It,” Newsweek, July 23, 2020, https://www.newsweek.com/key-defeating-covid-19-already-exists-we-need-start-using-it-opinion-1519535.
(4) Dr. Hemal N. Sampat et al, “Coming Clean About Hydroxychloroquine,” Newsweek, August 20, 2020. https://www.newsweek.com/coming-clean-about-hydroxychloroquine-opinion-1526225. The opinion essay was signed by a total of nineteen medical doctors.
(5) Derek K. Chu et al, “Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis,” The Lancet, June 27, 2020; 395: 1973–87, https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2931142-9.