How Evidence-Based Medicine Conducts Controversial Clinical Trials
How Evidence-Based Medicine Conducts Controversial Clinical Trials
Anonim

I understand perfectly well that most people on the Internet are no longer able to read an article from more than one page of a Word document. It’s not that important. Without a brief description of what is called "evidence-based medicine" in the modern world, it will be difficult to argue some of the things that modern bureaucrats from science called "pseudoscience."

In fact, the term "pseudoscience" is pseudoscientific in itself, I beg your pardon for the pun. There is no such thing as pseudoscience. There is a scientific methodology, there are studies that either correspond to it or do not correspond to it. Any set of phenomena has a right to exist. Any hypothesis explaining these phenomena has a right to exist. And this hypothesis becomes a science or not a science only when in pure experiments with a high probability the real possibility of the existence of such facts is proved and it is possible to predict these facts with the same high probability.

That is, a negative result of an experiment is not proof of the absence of a fact. But the existence of a fact can only be confirmed by a positive experiment repeated under certain conditions.

So - let's talk about such a phenomenon as Evidence-Based Medicine.

Not so long ago I had to speak on a radio program on the topic of the current state of medical science. At the same time, I had to talk to one fairly well-known physician - a doctor with extensive experience, both in the hematological and surgical clinics, and the ambulance.

For some reason, we are talking not only about the modern throwing of our officials from medicine, but also about the scientific method. The so-called "evidence-based medicine" was mentioned. And it was at her mention that the doctor gently gave out everything that he thinks about this. As it turned out later, when communicating with a number of other physicians, the opinion of the majority of “evidence-based medicine” is the most negative. But the problem is that this direction is highly valued by officials and popularizers (especially Western ones), as a super-weighty argument when beating off significant amounts in the process of certification or prohibition of certain medical methods, certain pharmacological agents, certain state campaigns for the promotion of medical products.

Having examined carefully what the concept itself and the methods of its use are, I also imbued with the feelings of medical workers.

Simply because I can imagine what the method of a normal experiment is and what exactly the officials from medicine of all stripes are pushing under the guise of it.

To begin with, I went the simplest way - by simply looking at the definitions from the notorious Wikipedia. Why? Because it is the wiki style that is characteristic of the overwhelming semantic field of what is called "real science" abroad, and besides, it is this style that is imposed in modern Russia as the basic one.

Let's start with simple quotes:

At the same time, there is one more subtle point that is indicated in that article:

Now let's think about what kind of concept is being carried out as a basic one.

Here is a link to an article by a certain A. Li Wan Po, University of Nottingham, UK (there is a strong association at once on the topic “British scientists have proved”, but this is a classic untranslatable pun characteristic of the critical sector of the Russian-speaking Internet).

The article is titled "Pharmacology - Evidence-Based Pharmacotherapy".

The criterion of evidence is given:

“According to the Swedish Council on Technology Assessment in Healthcare, the quality of evidence from these sources varies in reliability and decreases in the following order: 1) a randomized controlled trial; 2) a non-randomized concurrent trial; 3) non-randomized historical control trial; 4) cohort study; 5) a case-control study; 6) cross test; 7) the results of observations; 8) description of individual cases ".

It seems that everything is fine, but on the other hand, “evidence”, which is quite scientifically evaluated from the point of view of a classical experiment, and “evidence”, which are based on such ephemeral signs as “patient's feelings”, turned out to be in a single system.

Here, for example, is a quote from the same source: “What, for example, is understood by the severity of herpes infection when treated with acyclovir ointment? Should it be assessed by objective (lesion area) or subjective (pruritus, pain) parameters? How do they compare with the overall rating? Is it better to pick one overall grade? In dermatology, preference is usually given to the opinion of the patient himself, although in some studies the severity of itching was assessed by a doctor. When analyzing the results of treatment of chronic diseases, it is important to neglect the immediate effect and try to evaluate the less visible but probably more important aspects of therapy, in particular its impact on the quality of life of patients. Moreover, it is necessary to check the information content of methods for assessing the quality of life. The process is time consuming and expensive, but the results obtained with untested methods are unlikely to be of practical value."

Further - we simply give considerations of a purely scientific and paradigmatic nature.

There is a certain pharmacological agent. This remedy is positioned as a remedy for certain diseases. To be more precise, it is recommended for certain diseases, since it affects one or another parameter of the disease process. (I will make a reservation in advance - as a person with a purely engineering scientific approach, I try to identify the logic of a systemic nature).

So, a certain pharmacological agent (or therapeutic method), which should return one or another functional process of the organism to the framework of the homeostatic corridor, which is normal for this organism, that is, allowing the entire organism to function as “healthy”.

And here the strange begins.

When a certain effect is exerted on the body, say, by a certain substance, it is assumed that this substance has the same (!) Effect on a particular process (specific for a given substance) on any person. But this, of course, is the ideal. Since everyone knows that a substance that has an identical effect in any case simply does not exist.

If we take a simple chemical reaction, for example, the effect of an acid solution on an alkali solution of specific types, then such reactions have been described for a long time and in detail. In this case, the very mechanism of interaction of substances is taken into account in rough terms, as well as the conditions under which it can proceed. Well, let's say, the temperature (on which the rate of the reaction proceeds), the volumes of the reactants, the residual quantities of unreacted substances, the purity of the drugs used, and much more.

That is, already in the variant of the simplest interactions, an interesting thing comes to light: the parameters of a chemical reaction depend not only on the nature of the reacting chemicals themselves, but also on a set of additional conditions. Let me emphasize - significant conditions.

Even more difficult - by orders of magnitude - is the situation when a certain substance begins to work in the body.

It is of paramount importance to understand that an organism is not a set of biochemical reactions that work autonomously and each independently.An organism is a system in which literally all subsystems, at all levels - from the cellular to the social - work in a complex relationship.

(For illustration purposes only, I recommend the book Nefedov, Novoseltseva, Yasaitis "Homeostasis at various levels of the organization of biosystems").

And with different values ​​of mutual influence, all systems of different organisms will react differently. Yes, in many cases certain reactions may fall into a certain field of similarity, but in general …

Here's a simple example. There are reactions to the pharmacopoeia that are different for women and for men. For example, progesterone, which is important both in the body of men and in the body of women, affects similar biochemical processes, however, it produces completely different effects on the organisms of people of different sexes. (I will not go into details, since everyone is able to see for himself how the effect of this hormone on organisms of different sexes differs).

And this is one of the simplest examples.

If we start looking further, we see that complex pharmacology has different effects on organisms, which are different:

- floor, - age, - type of central nervous system, - type of peripheral nervous system, - type of bilateral asymmetry, - the type of dominant frontal-occipital gradient, - blood type, - Rh factor.

And so on and so forth.

In addition, there is a significant difference in the rate of reaction to pharmaceutical exposure in people with different psychological and social experience of response, both to their own disease and to the treatment process itself. Plus the factor of the degree of the disease - initial, medium, severe.

Now let's look at the main thing.

In order to assess the factor of influence of a new drug (treatment method, diagnostic method), a clinical study is required, as required by "evidence-based medicine" in category, say "A" (I), it is necessary to conduct several (!) Studies based on double blind method, excluding placebo effect. Moreover, it should be carried out both on patients with whom the drug is intended, and on healthy people, in order to assess the degree of "pure" effect of the substance, which changes the homeostasis corridor of the target factor.

Here is an excellent article that provides some insight into the methods of selecting representative populations for statistical evaluations of selected parameters in clinical trials. "Clinical trial and clinical study: similarities and differences"(G. P. TIKHOVA, Republican Perinatal Center, Petrozavodsk,).

The beauty of this approach lies in a real qualitative assessment of the size of a representative group based on a small number of parameters. But let's estimate how much, in fact, it is necessary to carry out evaluations in the study of the effect of complex drugs or methods of influence on the body in real and honest "evidence-based" studies.

Let's take up the simplest arithmetic.

To be sure that the study group is really similar in all significant parameters, it is necessary to select it in such a way that all the specified differentiations coincide.

So, let's begin.

"Boy - Girl" are two different groups.

“Age Groups” are a minimum of six (for simplicity).

There are four groups according to the type of the central nervous system (type of temperament, type of information-motivational response according to P.V. Simonov).

There are two groups according to the type of dominant of the peripheral nervous system.

There are two groups according to the difference in bilateral brain asymmetry.

There are two groups according to the difference in the dominance of the frontal-occipital grandeur.

There are four blood groups.

There are two groups according to the Rh factor.

On this I, perhaps, will stop, although it is possible for a long time to count how many variants of the biochemical response can be with different variants, for example, the correspondence of the psychophysiological type and the psycho-social, but this is already real - a deaf jungle that modern medicine practically does not study and does not really know what it is.

Therefore, we simply consider: 2x6x4x2x2x2x4x2 = 3072

That is, to assess the impact of any new drug or method, it is necessary (within the framework of “evidence-based” medicine!) To conduct 3072 studies. We multiply this number by the number of patients in a representative group. In this case, we will take the size of such a group on average equal to 40 (forty) people. Yes, this is very approximate, in the above article it is shown exactly how the sampling process is carried out, but, as a rule, this number is considered quite significant and reliable. At least in the good old days it was.

Although, allowing myself to make a small lyrical digression, it is somewhat stressful at the moment. For example, talking with a nice woman, head. Department of cytohistology at one very famous university, I was surprised to learn that at the present historical stage, when writing candidate and doctoral dissertations in the field of medicine, a representative group of … 3-5 people is sufficient.

I would have laughed myself if it weren't so awful.

But let's continue.

So, we take a group with the same parameters of forty souls and multiply this number by 3072. We get - 122,880 people. Yes, I forgot, we multiply this number by two, since we also need a control group.

Total - 245,760 people.

Yes Yes. This is exactly how much, in theory, is needed to conduct relatively rough studies (in one pass, which is typical!), To assess the effect of a particular pharmaceutical or medical method, so that they are reliable within the framework of "evidence-based medicine" of class "A" (I).

By the way, this number must be multiplied by at least two (2) in order to just get into this class. (Remember? "Data from a meta-analysis of SEVERAL randomized controlled trials.").

But, as they say in advertising for cheap kitchen knives, "and that's not all!"

Do not forget that people are also divided into races and racial subgroups according to their biochemical, physiological, psychological properties.

This means that this number must be increased by a certain number of times. From three (minimum) to 10-15. On average, so as not to be very confused in numbers - by four. Hence the number of subjects is about a million! 1,000,000.

Imagine the size of the disaster?

And this is only if preliminary studies have already been carried out on the selection of people according to these categories, taking into account whether they are sick with the target disease or not.

That is, in order to select the test groups, it is necessary to sift through the "flap sieve" the number of people by an order of magnitude - two more. Not a million, but a hundred million. 100,000,000.

And we have not yet mentioned such characteristics that, in principle, are generally taken into account by doctors, but by no means always taken into account in statistical studies. For example - what are the actions preceding the test. Did the subject take antibiotics, narcotics, tranquilizers, etc. before the test? After all, we are talking specifically about people who are sick, that is, those who, in one way or another, are subjected to some therapeutic action in addition to testing.

And this we have not yet mentioned about individual or group conditions, when conducting a particular test program.

But we will not even take these figures into account, since all this is very vague. We will just know that there is a margin of "scientific" approach to research.

But let's see how much resources are spent on conducting clinical trials and how many trials are being conducted in general.

For example, here's the data:

(For reference, R & D projects are their foreign version of our R&D - research and development. Research and development).

Let's imagine that all these 10, 5 thousand projects are not going sequentially, but sequentially and in parallel.

Let's arbitrarily reduce the number of simultaneous studies by an order of magnitude. I think that I will not be very mistaken.That is, we multiply the preliminary number of test researchers by another thousand.

In total, that is, already about ten billion. 10,000,000,000.

Let's say that the number of pharmaceutical companies that actually research new drugs (which, of course, greatly simplifies the calculations, but does not correspond to reality, but - nevertheless …) is limited to only fifty major world ones.

And let's say that all campaigns use the mentioned number of trial patients not new for each study, but at least fifty percent of the same (which, frankly, is unlikely, since everyone has different diseases and target groups of pharmacological drugs - different).

We multiply ourselves. It is possible in the mind. You can use a calculator.

Have you appreciated the figure?

This is a purely arithmetic, purely engineering and purely logical approach to the very concept of evidence-based science.

Yes, there are fewer people on Earth now. It's just that the given number of studies is really necessary for a real scientific assessment of the reliability of the so-called "evidence-based medicine".

In general, for really scientifically significant research in the framework of "evidence-based medicine", only immeasurably more human resources are required than there are people on the planet.

No, no, I am aware that, with a high degree of probability, many research parameters "collapse", that is, when the body is exposed to certain drugs or techniques, some separation categories may well show (and show in reality) similar values.

But even if we reduce the total number of studies by a couple of orders of magnitude, it still becomes obvious that there can be no question of any real reliability when conducting such studies.

And one more significant point. Repeatedly I had to deal with a situation when some conceptual circuit solutions based on the real properties of the instruments used and the real characteristics of the patients encountered opposition from those who had to implement the assessment algorithms - mathematicians and programmers. Here the situation turned out to be strange. Being absolutely sure that it is the methods of mathematical statistics that are the absolute tool for solving the problem of assessing the state, they managed to make statements of this kind: are they characteristic?"

Something similar, but from the side of the doctors, researchers also sounded. In the sense - why should the patient's characteristics be taken into account if there are methods of mathematical statistics? But here, as I understand it, a certain religious feeling comes to the fore that a non-specialist experiences in relation to an instrument, the whole essence of which he does not know, but it was explained to him that this is great in itself.

Thus, we will try to summarize.

The idea of ​​scientific evidence in any research that evaluates the influence of certain factors on a person's condition is correct and deserves the warmest support.

But the forms that we observe in reality indicate that in reality we have not so much "evidence-based medicine" as classical speculation based on certain collusion of stakeholders and at a high level of medical, mathematical and general scientific illiteracy of the population in the whole.

In addition, one should not forget that any methods in modern science in no case can remain aloof from the social factor of influence. No "evidence-based medicine" is in any way able to cope with the real goals and objectives that production capital sets itself in order to maximize profits.Naturally, any pharmaceutical forms that are more expensive, but less effective, will have a clear priority over those, but more effective and cheaper. Do not forget that medicine at the present time is not so much striving for the healing of patients as in their long-term treatment.

That is, all versions of the modern meme "British scientists have proved" for the next few decades will remain just socio-political memes, which have a very indirect relationship to real science.

Here it would be appropriate to point out one more factor capable of casting a very strong doubt on what is called modern science in general.

This factor is the purposeful introduction of an element of profanation and outright deception into scientific activity on the part of some researchers who are not so much interested in scientific research itself as in their material equivalent and scientific fame that they personally receive. And the attitude of a certain clannishness of scientific communities, which are ready to contribute to the outright profanation of scientific research.

Here, for example, a recent scandal on this topic:

"A scandal in the scientific world: fake research is winning real awards"(From 20.01.2019 last call)

Well, criticism of certain methods that are not related to the business of leading medical firms will always be based on the interests, first of all, of the business. And the health of people or real scientific innovations will always remain in the last place.

Therefore, I recommend that everyone who appeals to some kind of "evidence-based medicine" in arguing certain approving or critical assessments should be calmly ignored, since in the coming years this phenomenon will remain exclusively an instrument of sociological, political and commercial manipulation and speculation.

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