2024-10-15 15:08:00
Over the course of health scams and scandals that have occurred since the 19th century, the question of proof in medicine has gradually become central. If evidence-based medicine seems to have established itself over the past few decades, the recent controversies that have arisen during the Covid-19 pandemic remind us that this “golden standard” is not yet always self-evident…
How to evaluate the effectiveness of a medical treatment? In 1865, the pioneer of modern medicine, the French physician, physiologist and epistemologist Claude Bernard, the question was already being asked in these terms: “how can we know if it is the remedy or nature that has cured? »
Since that time, the standards of evidence for evaluating the effectiveness and safety of medical treatments have evolved significantly. A break took place in the 1990s with the advent of “evidence-based medicine”, in response to stricter regulation of medicines. But what exactly are we talking about?
The emergence of legislation regulating medicines
The United States was a pioneer in the development of drug regulation. This is why they will serve as a reference in this article.
William Radam, and 1890.
commons.wikimedia.org/wiki/File :William_Radam.png
Until the beginning of the 20th century, there was no control over the production and sale of medicines. In 1886, remedies such as « Microbe Killer » of William Radham believed to cure all diseases. To promote his product, Radam used innovative marketing, placing advertisements in newspapers and writing several books. Exploiting the interest in microbes following the discovery of the agent of tuberculosis by Robert Koch in 1882, he exhibited in « Microbes and the Microbe Killer » his theory of a single origin to all diseases as well as the enthusiastic testimonies of those who had used his product. The Microbe Killer enjoyed great success and was sold all over the world.
In 1902, an analysis carried out by the Bureau of Chemistry of the Department of Agriculture headed by the chemist Harvey Washington Wiley revealed that the Microbe Killer was made of nothing but water, sulfur, and diluted sulfuric acid.
The studies carried out by the Wiley team, nicknamed the “poison brigade”also demonstrated the toxicity of certain food preservatives commonly used at the time, such as boric acid, borates (salts or esters of boric acid) and formaldehyde (formalin), as well as the toxicity of common remedies, such as THE Calomel and the « Mercury bichloride »two remedies used against syphilis which contained mercury, a heavy metal with particularly deleterious effects on health. These studies highlighted the urgency of a federal food and drug law.
Advertisements for William Radam’s “Microbe Killer”.
NIH/Wikimedia
Furthermore, in 1906, the publication of the novel « The Jungle » by journalist Upton Sinclair, who denounced the unsanitary practices of the food industry, sparked a public lobbying for government regulation. It was this same year, 1906, that saw the adoption by the American Congress, after more than 200 rejections in 27 yearsfrom the text of the law « Pure Food and Drugs Act » which finally prohibited the misleading labeling of foods and medicines. It led to the creation of the Food and Drug Administration (FDA), whose missions are to ensure the safety of foods and drugs, their honest and accurate labeling, as well as to prosecute fraud.
In 1937, Elixir Sulfanilamide, a sulfonamide antibiotic, caused mass poisoning and death of more than 100 people in the United States. The scandal led in 1938 to the adoption of the Federal Food, Drug, and Cosmetic Act which introduced a requirement for drug manufacturers to demonstrate that the drug is safe for human use.
However, this law did not yet make it possible to withdraw from the market the many inherently dangerous drugs that were already present there and its ability to prevent the introduction of new problematic preparations was limited. In fact, the FDA only had 60 days to prove the dangerousness of a new drug and prevent its marketing. In addition, it did not have the power to enforce good manufacturing practices.
Photograph, taken around 1972, of Terry Wiles (right), suffering from phocomelia due to thalidomide taken by his pregnant mother.
Wikimedia
It took a new tragedy, that of thalidomide, for the legislation to be strengthened. Sold in the 1950s as a sedative and anti-nausea intended for pregnant women, this drug was associated with serious congenital malformations in thousands of newborns in Europe. This drama pushed the American Congress to adopt the amendment in 1962 Kefauver-Harris.
This required that any drug be evaluated before being placed on the market and demonstrate its effectiveness and safety through rigorous clinical studies.
In Europe, before the creation of the European Union (EU), each country had its own legislation. There Directive 65/65/EEC of January 26, 1965 introduced uniform requirements for the registration of medicines. But it was not until 1995 that was created the European Medicines Agency (EMA), whose main mission is to authorize and control medicines in the EU.
Evidence-based medicine
In 1972, Archibald Leman Cochrane published a important critical report on medical practices. He demonstrated the weaknesses of medical decisions based on the doctor’s personal experience, always limited and subjective, and recommended carrying out controlled clinical trials in order to more objectively evaluate each treatment.
In a controlled trial, the effect of a drug is compared to that of a placebo, an “inert” substance that resembles the drug but contains no active ingredients. A drug is only considered effective if its positive effects for the patient are significantly greater than those of the placebo.
Many refinements emerged to increase the reliability of the tests. In “randomized and double-blind” (or “double-blind”) trials, the participants receiving the placebo or the drug are chosen at random, and neither they nor the researchers know what treatment is being administered.
This practice reduces the risk that participants’ expectations or researcher biases will influence study results, due respectively to the placebo effect and confirmation bias (the tendency to give more weight to information that confirms our beliefs than to those which invalidate them).
As a result, in 1980, the FDA required that proof of a drug’s effectiveness be obtained. from randomized double-blind placebo-controlled trials. These became the “gold standard” (highest standard) for the evaluation of medical treatments.
However, it was not until the 1990s, with the democratization of computers and the development of data banks accessible via the Internet, that the practice of evidence-based medicine. This one is defined by one of its pioneers, David L. Sackettas “the conscientious, explicit, and judicious use of the best current evidence in making decisions about patient care.”
A pyramid of evidence
The construction of medical consensus in evidence-based medicine is based on two main principles: the analysis of all the studies available in the databases and the prioritization of these.
This hierarchy is often presented in the form of a evidence pyramid where follow-up studies of cohorts of several thousand individuals over time and controlled and randomized clinical trials have more value than expert opinions and simple analyzes of clinical cases.
The evidence pyramid of evidence-based medicine.
Wikimedia Commons, CC BY
Meta-analyses, statistical analyzes that combine the results of several clinical trials, complete the picture. They are considered to be the most reliable source of evidence.
L’ONG Cochrane
The need to organize all the information concerning medical research and communicate it to doctors to lead to the emergence oforganisation Cochrane. A non-profit non-governmental organization (NGO), it brings together tens of thousands of volunteers in more than 130 countries and has a headquarters at the World Health Organization.
Cochrane evaluates available clinical trials and meta-analyses to produce clinical practice guidelines which it then communicates to doctors. His work is published in the Cochrane Library and are regularly updated.
Presentation of the Cochrane organization.
The current medical consensus is still expected to evolve significantly. Indeed, if we refer to the standards of medicine based on modern evidence, the Most medical interventions (94%) are not supported by high-quality evidence.
A paradigm shift still poorly accepted
The principles of evidence-based medicine have made medicine a science. They broke with the “art medicine” practiced since ancient times, which was characterized by the fact that the choice of treatment was largely based on the personal experience and intuition of the doctor.
However, this change is not yet unanimously accepted. Thus, during the SARS-CoV-2 pandemic, we witnessed violent media controversies concerning hydroxychloroquine and vaccines against Covid-19. Evidence-based medicine has been accused by some of being at the service of the pharmaceutical industry and contrary to medical ethics (this thesis was notably defended by the microbiologist Didier Raoult and the sociologist Laurent Mucchielli).
However, as we have seen, the development of evidence-based medicine is not a consequence of industry pressures. On the contrary, its lobbyists have often opposed the establishment of restrictive legislation on medicines, because carrying out clinical trials delays their marketing and represents a very significant cost.
Remember that the average cost to validate a treatment is estimated at 33 million dollars, and that more than 90% of candidate medical treatments fail to cross the “valley of death” of clinical trials, the objective of which is to demonstrate their safety and effectiveness.
Of course, evidence-based medicine is not perfect: it remains fallible, and always gives rise to critiquesparticularly because of the risks of conflicts of interest due to industry funding of clinical trials.
To improve its reliability, various avenues have been proposed, for example promoting the publication of negative results in scientific journals, or strengthening the independence of universities and researchers through better funding. In the meantime, in its current form, it is the most effective thing we have to evaluate the effectiveness of medical treatment, fight against quackery and reduce the risk of health disasters.
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