Clinical drug trials, perhaps one of the most mythologized areas of modern pharmacology. It would seem that companies spend years of work and fabulous money to study the effect of a particular drug formula on the human body and put it on sale, but many are still convinced that the matter is unclean and pharmaceutical companies set their own goals exclusively. To dispel the most popular myths and understand the situation, the medical portal "MED-info" spoke with Lyudmila Karpenko, head of the department of medical research and information of one of the leading domestic pharmaceutical companies.

The history of the emergence of the legal framework for clinical trials

In the narrowest sense, evidence-based medicine is a method of medical clinical practice, when a medical practitioner uses only those methods of prevention, diagnosis and treatment in a patient, the usefulness and effectiveness of which has been proven in studies performed at a high methodological level, and provides an extremely low probability of obtaining "accidental results."

Until the middle of the 20th century, in fact, there was no regulatory framework for research, and it arose after several major scandals in the use of understudied drugs. One of the most resonant was the case that resulted in the death of 107 children in 1937, when the M. E. Massengill company used diethylene glycol (a poisonous solvent, which is part of antifreeze for cars). No preclinical or clinical studies have been conducted. As a result, when it became clear that the drug was deadly, it was withdrawn from sale as quickly as possible, but by that time it had managed to claim more than a hundred lives, which prompted the US authorities to pass a law on mandatory drug research before they go on sale.

One of the main reasons that prompted the world community to develop universal rules for conducting clinical trials was the tragedy with thalidomide that occurred in the late 50s and early 60s. During tests on animals, in particular mice, the drug showed its best side and did not reveal any side effects, including in offspring. When the drug was used in pregnant women as a remedy for insomnia and toxicosis, it led to the birth of more than 10,000 children worldwide with defects in tubular bones and limbs. After that, it became obvious that full-fledged tests and studies should be carried out, and the experience of individual specialists cannot be a sufficient basis for registering the drug.

The first laws establishing state control over the production of drugs were adopted in Europe as early as the 1960s. Today, we are guided by the principles of the Declaration of Helsinki of the World Medical Association, which later became the basis for the International Harmonized Tripartite Guideline for Good Clinical Practice (ICH Harmonized Tripartite Guideline for Good Clinical Practice, abbreviated - ICH), which became the basis of local regulations since 1996/97 in the USA , Japan and the EU, and since 2003 introduced by the Order of the Ministry of Health of the Russian Federation No. 266 and in Russia (hereinafter - GOST R 52379-2005 "Good Clinical Practice").

The most common myths about conducting clinical trials:

1. testing new ones in public secretly

Today, when conducting research, we relentlessly follow the letter of the law, that is, the ICH document, according to which patients cannot be exposed to unreasonable risk, their rights and confidentiality of personal information are respected, scientific interest, as well as the interests of society cannot prevail over the safety of patients participating in the study, these studies are evidence-based and verifiable. “Compliance with this standard serves as an assurance to society that the rights, safety and well-being of research subjects are protected, consistent with the principles laid down by the WMA Declaration of Helsinki, and that clinical trial data are reliable.” Few people are protected in this process as much as the patient involved in it. In addition, before any procedure under the study protocol is performed, the patient receives full information about the study, possible risks and inconveniences, procedures and examinations within the study, investigational drugs, the likelihood of falling into one or another treatment group, learns about the presence alternative methods of treatment for their disease, is notified of their unconditional right to refuse to participate in the study at any time without any consequences, and signs an informed consent in the presence of a doctor, which documents the desire of a person to participate in the study. If something is not clear to the patient, the doctor is obliged to give additional explanations on the ongoing study. The patient also has the right to consult about his possible participation in a clinical trial with another specialist who is not part of the research team, or with his relatives and friends.

2. Pharmaceutical companies conduct clinical trials only in developing countries, where costs are lower and legislation is not as strict. For the global pharmaceutical industry, developing countries are a testing ground

First, with regard to the low cost of research in developing countries, this is not a completely correct statement. If we take Russia, which many experts attribute to developing markets, then the cost of conducting clinical trials of medicines in our country approaches and sometimes even exceeds the price level in Europe and the USA, especially when taking into account the current exchange rate. In addition, we have a huge country, which adds to the already impressive amount of costs significant logistics costs, as well as the payment of customs fees and duties, which are levied on drugs and other research materials imported into Russia.

Secondly, research in developing countries requires much more attention and control from companies, which complicates the whole process. Unfortunately, in developing countries there are not always enough qualified medical personnel who can work within the strict framework of the ICH, which requires the companies organizing the study to additionally invest in the training of clinic staff. On the other hand, in such countries, the population often does not have access to the latest medical developments and cannot receive free examination and treatment at the modern level, which is available to patients in developed countries. Therefore, sometimes participation in a clinical trial is the only way to get high-quality high-tech examination and treatment.

Thirdly, regardless of the legislation of a particular country, all studies must comply with the principles and standards of the ICH GCP in order to subsequently have the right to register the drug in the US, EU and other developed countries.

3. Clinical research is not safe for people. And the most dangerous phase I trials, when the drug is first used in humans, are carried out by pharmaceutical companies in developing countries.

First, let's understand the phases of any clinical trial. After preclinical studies and trials of the drug on biological models and animals, the so-called phase I begins - the first human trial, which is generally aimed at assessing the tolerability of the drug by the human body, it involves from several dozen to about 100 people - healthy volunteers. If the drug is highly toxic (for the treatment of oncology, for example), then patients with the corresponding disease take part in the study. As already mentioned, subject to research in developing countries, for many people there, this is the only chance to receive at least some kind of treatment. Phase II involves the participation of several hundred patients suffering from a specific disease, for which the investigational drug is intended to treat. The primary goal of Phase II is to select the most appropriate therapeutic dose of the study drug. And phase III is a pre-registration study involving already several thousand patients, usually from different countries, to obtain reliable statistical data that can confirm the safety and effectiveness of the drug.

Of course, Phase I trials are one of the most dangerous moments of the whole process. That is why they are carried out in specialized institutions, for example, departments of multidisciplinary hospitals specially equipped for such studies, where there is all the necessary equipment and trained medical personnel so that if something goes wrong, they can always respond quickly. Most often, these studies are carried out in the USA, Canada and the Netherlands, and in some countries they are limited or completely prohibited due to their unpredictability, as, for example, in India and Russia (we have a ban imposed on the study of foreign drugs involving healthy volunteers), which makes them impossible or difficult to implement on the territory of these countries.

4. Patients in clinical trials are guinea pigs, no one cares about them.

Few people are as protected in a clinical trial as the patient is. Do not forget that the main principles of research with the participation of people to this day remain voluntary participation and non-harm. All medical manipulations are performed only with the full knowledge of the person and with his consent. This is regulated by the already mentioned Declaration of Helsinki and ICH GCP. The protocol for conducting any clinical trial (and this is the main document), without which the study is impossible and which must be approved and approved by the Ministry of Health, regulates the interaction of the doctor with the patient, including the fact that the doctor provides all the necessary information in full and is responsible for the benefit/risk ratio for the study participant.

All patients participating in a clinical trial are under close medical supervision, regularly undergo various examinations, up to the most expensive ones, at the expense of the company conducting the study; all and any medical events, changes in health status are recorded and studied, with the development of adverse events, even those not related to the investigational drug, they immediately receive adequate treatment. In contrast, patients participating in clinical trials are in better health conditions than others.

The process also involves third-party observers from among the employees of the customer company or contract research organization who control its progress, and if the doctor suddenly violates the established procedure or exceeds his authority, they can initiate severe punishment up to stopping the study.

5. Patients in the control group receive a placebo - a drug - a "dummy", which puts their health and life at risk

It should be remembered that a placebo is an inactive substance that is indistinguishable from the drug under study only by external signs (appearance, taste, etc.), so, in fact, it cannot affect the human body in any way. However, for ethical reasons, the use of placebo in clinical trials is restricted in accordance with the principles of the Declaration of Helsinki. According to them, the benefits, risks, inconveniences, and effectiveness of a new treatment must be weighed against the best available treatments. The exception is when the use of a placebo in a study is justified because there is no effective treatment for the disease, or if there is a compelling evidence-based reason for using a placebo to assess the efficacy or safety of the study treatment. In any case, patients receiving a placebo should not be at risk of causing serious or irreversible harm to health. In addition, a patient participating in a clinical trial is under the close supervision of highly qualified specialists and has access to the most modern drugs and technologies, which makes the risks minimal.

6. Clinical research is overkill. For the release of the drug on the market, information obtained in the course of preclinical trials of the drug on biological models and animals is quite enough.

If that were the case, pharmaceutical companies would have stopped spending billions of dollars on human research long ago. But the thing is that there is no other way to understand how a particular drug affects a person, except to conduct an experiment. It must be understood that the situation modeled in the course of preclinical studies on biological models is, in fact, ideal and far from the real state of affairs. We cannot predict how a particular dose of the drug will affect people with different body weights or with different comorbidities in history. Or how the drug will act on the human body in different dosages, how it will be combined with other drugs. All of this requires research involving humans.

The commercial interests of pharmaceutical companies come into conflict with the need to carefully monitor the progress of clinical trials and obtain reliable scientific data.

Pharmaceutical companies spend billions of dollars on clinical trials for drugs, most of which may never reach the market. In addition, the progress and results of the study are closely monitored by public health authorities, and if they are not completely confident in the quality and reliability of the data obtained, the drug will not be registered, will not enter the market and will not bring profit to the company. So careful control over the study is, first of all, the interest of the customer company.

7. In Russia, many untested drugs are sold in pharmacies, only foreign countries conduct thorough research before bringing drugs to the market

Any clinical trial (CT) is carried out only with the permission of the state authorized body (in the Russian Federation this is the Ministry of Health of the Russian Federation). The decision-making procedure provides for the analysis of documents submitted by the drug development company, including those on conducting clinical trials, by special expert bodies - on the one hand, clinical pharmacologists, and on the other hand, the Ethics Council specially created under the Ministry of Health of the Russian Federation. The fundamental point is precisely the collegiality of decisions and the competence of persons making an independent decision. And just as strictly regulated is the decision-making procedure based on the results of clinical trials, which are considered by experts of the Ministry of Health of the Russian Federation for the completeness and quality of the studies performed, and the achievement of the main goal - to obtain evidence of the effectiveness and safety of using the drug for its intended purpose. It is at this stage that it is decided whether the results obtained are sufficient for registration of the drug or whether additional studies are required. Russian legislation today is not inferior in terms of the level of requirements for conducting and evaluating the results of clinical trials to the regulations of the leading countries of the world.

Post-registration studies. How and for what purposes they are carried out

This is an extremely important stage in the life of any drug, despite the fact that post-registration studies are not required by the regulator. The main goal is to ensure the collection of additional information on the safety and efficacy of the drug on a sufficiently large population for a long time and in "real conditions". The fact is that, in order to ensure a homogeneous sample, clinical trials are conducted, firstly, on a limited population and, secondly, in accordance with strict selection criteria, which usually does not allow, before registration, to assess how the drug will behave in patients with various concomitant diseases, in elderly patients, in patients taking a wide range of other drugs. In addition, given the limited number of patients involved in clinical trials at the stage of pre-registration study of the drug, rare side effects may not be registered simply because they did not occur in this cohort of patients. We will be able to see and identify them only when the drug enters the market and a sufficiently large number of patients receive it.

When a drug is marketed, we must closely monitor its fate in order to assess and study the most important parameters of drug therapy, such as interaction with other drugs, effects on the body with long-term use and in the presence of diseases of other organs and systems, for example, the gastrointestinal tract , history, analysis of the effectiveness of use in people of different ages, identification of rare side effects, and so on. All these data are then entered into the instructions for use of the medicinal product. Also, in the post-registration period, new positive properties of the drug may be discovered, which in the future will require additional clinical studies and may become the basis for expanding the indications for the drug.

If the drug detects previously unknown dangerous side effects, then its use may be limited up to the suspension and withdrawal of registration.

The concept and types of biomedical research

Human studies are divided into two types:

1) biomedical research (non-clinical)

2) clinical studies.

Medico-biological studies study the reaction, change in the state of the body of healthy people when exposed to certain external factors. Such studies supplement and improve scientific data, but they are not directly related to the treatment of diseases.

Clinical studies are carried out in the treatment of diseases. These studies are carried out according to clear rules, excluding moments that distort the result. To determine the effectiveness of medical treatment, experimental and control groups are needed, the number of subjects in each group should be at least 100, in order to identify clear analogies, the groups should be approximately the same in age, sex, and severity of the disease. Any research is ethical when it is meaningful, well organized.

The normal development of medicine is impossible without ongoing clinical trials and biomedical experiments on humans.

At the same time, no matter how high the value of objective knowledge, it must in all cases be commensurate with no less, and often more significant social values, which can be formulated in the form of principles:

respect for a person as a person;

charity and mercy;

justice;

solidarity.

The main ethical principles for conducting medical research are as follows:

1. Respect for a person as a person comes from the recognition and respect for the self-sufficient value of his free will, the right and opportunity to play a decisive role in making decisions affecting his bodily and (or) social well-being.

2 Fairness presupposes the fundamental equality of opportunities for people in terms of: a) the availability of medical care and distributed medical services; b) probabilities to share the burden of risk to health and life, suffering and responsibility.

3. . Only such human studies can be morally justified, which, in their ideology, methodology and methodology, correspond to the standards of modern medical science.

4 Clinical trials and biomedical experiments on humans can only be carried out by a team of specialists led by a doctor, corresponding to the nature of the examination of the qualification.

Rules for the regulation of biomedical research.

1) Tests and experiments begin subject to the complete and accessible information of the patient and obtaining his explicit consent, expressed in writing.

2) The investigator must guarantee the patient's right to refuse to continue the study at any stage and for any reason. The subject can feel not only physical pain, but also emotional discomfort, fear, prejudice. If the test is detrimental to the health or life of the patient, it must be terminated immediately.

3) If the patient is unable to give informed consent to participate in the study, it may be obtained in writing from a parent, guardian or other legally responsible person.

Biomedical research on humans can be carried out by doctors in the following cases:

1) if they serve to improve the health of patients participating in the experiment;

2) if they make a significant contribution to medical science and practice;

3) if the results of previous studies and scientific literature do not indicate a risk of complications.

Animal experiment is required:

1) in cases where animal populations are studied;

2) in those cases in which, according to the conditions of the experiment, it is necessary to study the reaction of the whole organism, the mutual influence of organs and systems, the sequence of failure (or healing) of various organs and systems;

3) when conducting final experiments on the processing of new methods of surgical interventions;

4) when it is necessary to study the individual results of the impact;

5) when the organs and systems of the animal cannot be isolated;

6) - for research on isolated organs;

7) - when animals are used to obtain biological preparations (vaccines, serums, etc.).

Given this circumstance, animal experiments must comply with strict ethical standards:

1) the goals are approved by society and the ethics committee, based on the principle of humanism;

2) effective anesthesia is applied;

3) necessary care is provided;

4) animals are not used in repeated experiments that turn their life into continuous suffering;

5) death is painless;

6) experiments are carried out by trained persons in order to avoid unnecessary suffering;

International ethical and legal regulation of biomedical research:

- The "Nuremberg Code" on biomedical research on humans and the "Declaration of Helsinki" of the WMA as the fundamental sources of modern moral norms for conducting experiments and clinical trials on humans.

- Council of Europe Convention on Human Rights and Biomedicine.

1. "Nuremberg Code"

The modern history of the discussion of these problems begins, perhaps, with the end of the Second World War.

The peculiarity was in the particularly cruel, inhuman nature of the experiments, which was that they actually planned the death of the subjects. The experiments carried out by the Nazis are described below:

1) as a study of the reaction of the body to high altitudes and rarefied air: on the subjects - prisoners of the Dachau concentration camp - the effect of a lack of oxygen in atmospheric conditions at an altitude of 12 km was simulated. Usually the subject was dead within half an hour; at the same time, in the protocol of the experiment with German pedantry, the stages of his deathbed torment were recorded (such as "spasmodic convulsions", "agonistic convulsive breathing", "groans", "shrill cries", "grimaces, biting one's own tongue", "inability to respond to speech" and so on.)

2) The reactions of the body to hypothermia were also studied, for which naked subjects were kept in frost up to 29 degrees for 9-14 hours or immersed in ice water for several hours.

3) During the experiments, carried out mainly on women in the Ravensbrück concentration camp, wound infections were studied, as well as the possibilities of bone, muscle and nerve regeneration and bone transplantation. Incisions were made on the subjects' legs, and then bacterial cultures, pieces of wood shavings, or glass were injected into the wounds. Only a few days later, the wounds began to heal, checking one or another means. In other cases, gangrene occurred, after which some subjects were treated, while others - from the control groups - were left without treatment.

4) In other experiments on prisoners of concentration camps, infectious jaundice was studied; methods were developed for cheap, insensitive and rapid sterilization of people; mass infection of people with typhus was carried out; studied the speed and nature of the action of poisons; the effects on the body of phosphorus compounds contained in incendiary bombs were tested.

In the course of the Nuremberg trials, a document was developed, called the Nuremberg Code, which was, in essence, the first international document containing a list of ethical and legal principles for conducting research on people. It was prepared by two participating American medical experts, Leo Alexander and Andrew Evie, and became an integral part of the judgment handed down by the court.

The Ten Principles of the Code (may be repeated)

1. An absolutely necessary condition for conducting an experiment on a person is the voluntary consent of the latter.

2. The experiment must bring positive results to society, unattainable by other methods or methods of research; it should not be random, inherently optional.

3. The experiment must be based on data obtained in laboratory studies on animals, knowledge of the history of the development of this disease or other problems under study. Its implementation should be organized in such a way that the expected results justify the very fact of its implementation.

4. When conducting an experiment, all unnecessary physical and mental suffering and damage must be avoided.

5. No experiment should be conducted if there is reason to believe the possibility of death or disabling injury to the subject; an exception, perhaps, may be cases where medical researchers act as test subjects in their experiments.

6. The degree of risk associated with conducting an experiment should never exceed the humanitarian importance of the problem that the experiment is aimed at solving.

7. The experiment must be preceded by appropriate preparation, and its conduct must be provided with the equipment necessary to protect the subject from the slightest possibility of injury, disability or death.

8. The experiment should be carried out only by persons with scientific qualifications. At all stages of the experiment, those who conduct it or are involved in it require maximum attention and professionalism.

9. During the experiment, the subject must be able to stop it if, in his opinion, his physical or mental condition makes it impossible to continue the experiment.

10. During the course of an experiment, the investigator in charge of conducting it must be prepared to terminate it at any stage if professional considerations, good faith, and caution in judgment are required of him or her to suggest that continuation of the experiment could result in injury, disability, or death. subject.

Declaration of Helsinki- developed by the World Medical Association, is a set of ethical principles for the medical community regarding human experimentation. It was first drafted in June 1964 in Helsinki, Finland, and has since undergone nine revisions, the most recent of which was the Declaration extends the principles first articulated in the Nuremberg Code and applies these ideas directly to clinical research work.

(A couple of principles and rules of this declaration)

1) A doctor may combine medical research with the provision of medical care only if the research is justified by its potential preventive, diagnostic or therapeutic value.

2) The physician may combine medical research with the provision of medical care only if the research is justified by its potential preventive, diagnostic or therapeutic value, and if the physician has good reason to believe that participation in scientific research will not harm the health of patients acting as subjects research.

3) At the conclusion of the study, patients participating in the study have the right to be informed of the results of the study, as well as the right to enjoy any benefits derived from the study, such as access to interventions determined to be beneficial in the study, or access to other appropriate types of medical care or other benefits.

- Council of Europe Convention on Human Rights and Biomedicine. It includes

1. It is necessary to observe the principle of inviolability of private life, as well as to respect the right of a person to know (or not to know) information about the state of his health (Article 10).
2. Any form of discrimination based on information about the genetic characteristics of a person is prohibited

3. "The interests and welfare of the individual must prevail over the interests of society and science"

4. The collection of organs or tissues from a living donor for the purpose of their further transplantation can be carried out only with his consent and exclusively for therapeutic purposes (Article 19). By itself

5. The right of scientists to conduct scientific research must be respected, but the latter must be carried out in compliance with the provisions of this "Convention" and other legal instruments aimed at protecting the rights, dignity and interests of the individual (Article 15). Creation of human embryos for research purposes is prohibited

AND IN THE LECTURE YOU NEED TO GET INFO ABOUT WHEN IT IS POSSIBLE TO CARRY OUT RESEARCH WITHOUT THE CONSENT OF PATIENTS!!! SHE MADE ACCENT ON THIS

Planning and conducting clinical trials of medicines

Clinical trials of the medicinal product are a necessary step in the development of any new drug. At the initial stages of drug development, chemical, physical, biological, microbiological, pharmacological, toxicological and other studies are carried out on tissues (in vitro) or on laboratory animals.

These are the so-called preclinical studies, the purpose of which is to obtain, by scientific methods, estimates and evidence of the effectiveness and safety of medicines. However, these studies cannot provide reliable information about how the studied drugs will work in humans. Therefore, it is necessary to conduct clinical trials of drugs in humans.

Clinical study (test) of a medicinal product- This is a systematic study of a medicinal product through its use in a person (patient or healthy volunteer) in order to assess its safety and / or efficacy, as well as to identify and / or confirm its clinical, pharmacological, pharmacodynamic properties, assess absorption, distribution, metabolism, excretion and/or interactions with other drugs. The decision to start a clinical trial is made by

Sponsor/Customer who is responsible for organizing, supervising and/or funding the study. Responsibility for the practical conduct of the study rests with Researcher(person or group of persons). As a rule, the sponsors are pharmaceutical companies - drug developers, however, the researcher can also act as a sponsor if the study was initiated on his initiative and he bears full responsibility for its conduct.

Clinical research must be conducted in accordance with the fundamental ethical principles of the Declaration of Helsinki

Clinical Trials

clinical trial- scientific study of the effectiveness, safety and tolerability of medical products (including medicines) in humans. The Standard for Good Clinical Practice specifies the term as a full synonym for this term. clinical trial, which is, however, less preferred due to ethical considerations.

In healthcare clinical trials conducted to collect safety and efficacy data for new drugs or devices. Such tests are carried out only after satisfactory information about the quality of the product, its preclinical safety has been collected, and the relevant health authority / Ethics Committee of the country where this clinical trial is being conducted has given permission.

Depending on the type of such product and the stage of its development, researchers enroll healthy volunteers and/or patients initially in small pilot, "shooting" studies, followed by larger studies in patients, often comparing this new product with the treatment already prescribed. As positive data on safety and efficacy are collected, the number of patients typically increases. Clinical trials can range in size from a single center in one country to multicenter trials involving centers in many countries.

The need for clinical research

Each new medical product (drug, device) must undergo clinical trials. Particular attention was paid to clinical trials at the end of the 20th century, in connection with the development of the concept of evidence-based medicine.

Authorized control bodies

In most countries of the world, ministries of health have special departments responsible for verifying the results of clinical trials conducted on new drugs and issuing permits for the receipt of a medical product (drug, device) in a network of pharmacies.

IN THE USA

For example, in the United States, such a department is Food and Drug Administration (

In Russia

In Russia, the functions of oversight of clinical trials conducted in Russia are carried out by the Federal Service for Supervision of Health and Social Development (Roszdravnadzor RF).

Since the beginning of the era of clinical trials (CT) in the early 1990s, the number of studies conducted in Russia has been steadily growing from year to year. This is particularly evident in the case of international multicentre clinical trials (IMCTs), which have almost quintupled in number over the past ten years, from 75 in 1997 to 369 in 2007. The share of IMCTs in the total volume of clinical trials in Russia is also growing - if ten years ago they were only 36%, then in 2007 their share increased to 66% of the total number of clinical trials. This is an important positive indicator of the “health” of the market, reflecting the high degree of confidence foreign sponsors have in Russia as an emerging market for clinical trials.

Data obtained from Russian research centers is unconditionally accepted by foreign regulatory authorities when registering new drugs. This applies to both the US Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA). For example, six out of 19 new molecular substances approved by the FDA in 2007 underwent clinical trials with the participation of Russian research centers.

Another important factor in the increase in the number of IMCTs in Russia is the growth of its commercial attractiveness for foreign sponsors. The growth rate of the retail commercial market in Russia is three to four times higher than the growth rate of the pharmaceutical markets in Europe or the United States. In 2007, growth in Russia amounted to 16.5%, and the absolute volume of sales of all medicinal products reached 7.8 billion US dollars. This trend will continue in the future due to the effective demand of the population, which, according to the forecasts of specialists from the Ministry of Economy and Trade Development, will steadily grow over the next eight years. This suggests that if, through the joint efforts of market participants, Russia can approach the European deadlines for obtaining approvals for conducting clinical trials, then with its good set of patients and further stabilization of the political and regulatory climate, it will soon become one of the world's leading markets for clinical trials.

In 2007, Roszdravnadzor of the Russian Federation issued 563 permits for all types of clinical trials, which is 11% more than in 2006. The increase in indicators should be mainly attributed to an increase in the number of international multicenter clinical trials (IMCTs) (by 14%) and locally conducted clinical trials (up by 18% per year). According to the forecasts of the Synergy Research Group, which conducts quarterly monitoring of the clinical trials market in Russia (Orange Book), in 2008 the number of new studies will fluctuate at the level of 650, and by 2012 it will reach a thousand new CTs per year.

Control practices in other countries

Similar institutions exist in other countries.

International requirements

The basis for conducting clinical trials (tests) is the document of the international organization "International Conference on Harmonization" (ICG). This document is called "Guideline for Good Clinical Practice" ("Description of the GCP Standard"; Good Clinical Practice translates as "Good Clinical Practice").

In addition to doctors, there are usually other clinical research specialists working in the field of clinical research.

Clinical research must be conducted in accordance with the founding ethical principles of the Declaration of Helsinki, the GCP standard, and applicable regulatory requirements. Prior to the start of a clinical trial, an assessment should be made of the relationship between the foreseeable risk and the expected benefit for the subject and society. At the forefront is the principle of priority of the rights, safety and health of the subject over the interests of science and society. A subject may be included in the study only on the basis of voluntary informed consent(IS), obtained after a detailed acquaintance with the study materials. This consent is certified by the signature of the patient (subject, volunteer).

The clinical trial must be scientifically justified and described in detail and clearly in the study protocol. Assessment of the balance of risks and benefits, as well as review and approval of the study protocol and other documentation related to the conduct of clinical trials, are the responsibilities of the Expert Council of the Organization / Independent Ethics Committee (IEC / IEC). Once approved by the IRB/IEC, the clinical trial can proceed.

Types of clinical studies

Pilot the study is intended to obtain preliminary data that is important for planning further stages of the study (determining the possibility of conducting a study in a larger number of subjects, the sample size in a future study, the required research power, etc.).

Randomized a clinical trial in which patients are randomly assigned to treatment groups (randomization procedure) and have the same chance of receiving an investigational or control drug (comparator or placebo). In a non-randomized study, there is no randomization procedure.

controlled(sometimes synonymous with “comparative”) a clinical trial in which an investigational drug whose efficacy and safety has not yet been fully established is compared with a drug whose efficacy and safety is well known (comparator drug). This may be a placebo (placebo-controlled trial), standard therapy, or no treatment at all. In an uncontrolled (non-comparative) study, a control/comparison group (a group of subjects taking a comparator drug) is not used. In a broader sense, a controlled study refers to any study in which potential sources of bias are controlled (if possible, minimized or eliminated) (that is, it is carried out in strict accordance with the protocol, monitored, etc.).

When conducting parallel studies, subjects in different groups receive either the study drug alone or the comparator/placebo alone. IN cross studies, each patient receives both compared drugs, usually in random order.

Research can be open when all participants in the study know which drug the patient is receiving, and blind(masked) when one (single-blind study) or several parties participating in a study (double-blind, triple-blind, or full-blind study) are kept in the dark about the allocation of patients to treatment groups.

prospective the study is conducted by dividing the participants into groups who will or will not receive the investigational drug before the outcomes occur. In contrast, in a retrospective (historical) study, the outcomes of previous clinical trials are studied, that is, the outcomes occur before the study is started.

Depending on the number of research centers where the study is conducted in accordance with a single protocol, studies are single center And multicenter. If the study is conducted in several countries, it is called international.

IN parallel A study compares two or more groups of subjects, one or more of whom receive the study drug and one group is a control. Some parallel studies compare different treatments without including a control group. (This design is called independent group design.)

cohort a study is an observational study in which a selected group of people (cohort) is observed for some time. The outcomes of subjects in different subgroups of this cohort, those who were or were not treated (or were treated to varying degrees) with the study drug are compared. IN prospective cohort study cohorts make up in the present and observe them in the future. In a retrospective (or historical) cohort study, a cohort is selected from archival records and traced through their outcomes from then to the present. Cohort trials are not used to test drugs, but rather to determine the risk of exposure factors that are not possible or ethically controlled (smoking, being overweight, etc.).

In the study case control(synonym: case study) compare people with a particular disease or outcome (“case”) with people in the same population who do not have that disease or who do not experience that outcome (“control”), in order to identify an association between the outcome and prior exposure to certain risk factors. factors. In a case series study, several individuals are observed, usually receiving the same treatment, without the use of a control group. The case report (synonyms: case report, medical history, single case description) is a study of treatment and outcome in one person.

Double-blind, randomized, placebo-controlled trial- a method of testing a medical product (or treatment technique), which takes into account and excludes from the results the influence on the patient of both unknown factors and psychological influence factors. The purpose of the trial is to test the effect of the drug (or technique) only and nothing else.

When testing a drug or technique, experimenters usually do not have enough time and opportunity to reliably determine whether the tested technique produces a sufficient effect, so statistical methods are used in a limited clinical trial. Many diseases are very difficult to cure and doctors have to fight for every step towards recovery. Therefore, the test observes a variety of disease symptoms and how they change with exposure.

A cruel joke can be played by the fact that many of the symptoms are not strictly related to the disease. They are not unambiguous for different people and are subject to the influence of the psyche of even an individual person: under the influence of the doctor’s kind words and / or the doctor’s confidence, the patient’s degree of optimism, symptoms and well-being can improve, objective indicators of immunity often increase. It is also possible that there will be no real improvement, but the subjective quality of life will increase. Unaccounted for factors, such as the patient's race, age, gender, etc., can also affect the symptoms, which will also indicate something other than the effect of the investigational drug.

To cut off these and other effects that lubricate the influence of the therapeutic technique, the following techniques are used:

• research is being done placebo controlled. That is, patients are divided into two groups, one - the main one - receives the study drug, and the other, the control group, is given a placebo - a dummy.

• research is being done blind(English) single blind). That is, patients are unaware that some of them are receiving a placebo rather than an investigational new drug. As a result, patients in the placebo group also think they are being treated, when in fact they are receiving a dummy. Therefore, the positive dynamics from the placebo effect takes place in both groups and falls out of the comparison.

IN double blind(double blind) study, not only patients, but also doctors and nurses who give patients medicine, and even clinic management, do not themselves know what they are giving them - whether the study drug or placebo is real. This eliminates the positive impact of confidence on the part of doctors, clinic management and medical staff.

Clinical drug trials (GCP). Stages of GCP

The process of creating new drugs is carried out in accordance with the international standards GLP (Good Laboratory Practice Good Laboratory Practice), GMP (Good Manufacturing Practice Good Manufacturing Practice) and GCP (Good Clinical Practice Good Clinical Practice).

Clinical drug trials include the systematic study of an investigational drug in humans to test its therapeutic effect or to identify an adverse reaction, as well as the study of absorption, distribution, metabolism and excretion from the body to determine its effectiveness and safety.

Clinical trials of a drug are a necessary step in the development of any new drug, or expansion of indications for the use of a drug already known to doctors. At the initial stages of drug development, chemical, physical, biological, microbiological, pharmacological, toxicological and other studies are carried out on tissues (in vitro) or on laboratory animals. These are the so-called preclinical studies, the purpose of which is to obtain, by scientific methods, assessments and evidence of the effectiveness and safety of medicines. However, these studies cannot provide reliable information about how the studied drugs will act in humans, since the body of laboratory animals differs from the human body both in terms of pharmacokinetic characteristics and in the response of organs and systems to drugs. Therefore, it is necessary to conduct clinical trials of drugs in humans.

A clinical study (test) of a medicinal product is a systematic study of a medicinal product through its use in a person (patient or healthy volunteer) in order to assess its safety and efficacy, as well as to identify or confirm its clinical, pharmacological, pharmacodynamic properties, assessment of absorption, distribution, metabolism, excretion and interactions with other drugs. The decision to start a clinical trial is made by the customer, who is responsible for the organization, control and financing of the trial. The responsibility for the practical conduct of the study rests with the investigator. As a rule, the sponsor is pharmaceutical companies - drug developers, however, the researcher can also act as a sponsor if the study was initiated on his initiative and he bears full responsibility for its conduct.

Clinical trials must be conducted in accordance with the fundamental ethical principles of the Declaration of Helsinki, GСP (Good Clinical Practice, Good Clinical Practice) Rules and applicable regulatory requirements. Prior to the start of a clinical trial, an assessment should be made of the relationship between the foreseeable risk and the expected benefit for the subject and society. At the forefront is the principle of priority of the rights, safety and health of the subject over the interests of science and society. The subject can be included in the study only on the basis of voluntary informed consent (IC), obtained after a detailed acquaintance with the study materials. Patients (volunteers) participating in the trial of a new drug should receive information about the essence and possible consequences of the trials, the expected effectiveness of the drug, the degree of risk, conclude a life and health insurance contract in the manner prescribed by law, and during the trials be under constant supervision of qualified personnel. In the event of a threat to the health or life of the patient, as well as at the request of the patient or his legal representative, the head of clinical trials is obliged to suspend the trials. In addition, clinical trials are suspended in case of lack or insufficient effectiveness of the drug, as well as violation of ethical standards.

The first stage of clinical trials of drugs is carried out on 30 - 50 volunteers. The next stage is expanded testing on the basis of 2-5 clinics involving a large number (several thousand) of patients. At the same time, individual patient cards are filled in with a detailed description of the results of various studies - blood tests, urine tests, ultrasound, etc.

Each drug goes through 4 phases (stages) of clinical trials.

Phase I. The first experience with the use of a new active substance in humans. Most often, studies begin with volunteers (adult healthy men). The main goal of the research is to decide whether to continue working on a new drug, and if possible, to establish the doses that will be used in patients during phase II clinical trials. During this phase, researchers obtain preliminary safety data on a new drug and describe its pharmacokinetics and pharmacodynamics in humans for the first time. Sometimes it is not possible to conduct phase I studies in healthy volunteers due to the toxicity of this drug (treatment of cancer, AIDS). In this case, non-therapeutic studies are carried out with the participation of patients with this pathology in specialized institutions.

Phase II This is usually the first experience of use in patients with a disease for which the drug is intended to be used. The second phase is divided into IIa and IIb. Phase IIa is a therapeutic pilot study (pilot studies), as the results obtained in them provide optimal planning for subsequent studies. Phase IIb is a larger study in patients with a disease that is the main indication for a new drug. The main goal is to prove the effectiveness and safety of the drug. The results of these studies (pivotal trial) serve as the basis for planning phase III studies.

Phase III. Multicentre trials involving large (and possibly diverse) groups of patients (average 1000-3000 people). The main goal is to obtain additional data on the safety and efficacy of various forms of the drug, on the nature of the most common adverse reactions, etc. Most often, clinical trials of this phase are double-blind, controlled, randomized, and the research conditions are as close as possible to the usual real routine medical practice. The data obtained in phase III clinical trials are the basis for the creation of instructions for the use of the drug and for the decision on its registration by the Pharmacological Committee. A recommendation for clinical use in medical practice is considered justified if the new drug:

• - more effective than known drugs of similar action;
• - has a better tolerance than known drugs (with the same efficiency);
• - effective in cases where treatment with known drugs is unsuccessful;
• - more cost-effective, has a simpler method of treatment or a more convenient dosage form;
• - in combination therapy, it increases the effectiveness of existing drugs without increasing their toxicity.

Phase IV Studies are carried out after the start of the drug market in order to obtain more detailed information on long-term use in various patient groups and with various risk factors, etc. and thus more fully assess the strategy for the use of the drug. The study involves a large number of patients, this allows you to identify previously unknown and rarely occurring adverse events.

If the drug is going to be used for a new indication that has not yet been registered, then additional studies are carried out for this, starting from phase II. Most often, in practice, an open study is carried out, in which the doctor and the patient know the method of treatment (investigational drug or comparator drug).

In a single-blind test, the patient does not know which drug he is taking (it can be a placebo), and in a double-blind test, neither the patient nor the doctor are aware of this, but only the trial director (in a modern clinical trial of a new drug, four parties: the sponsor of the study (most often it is a pharmaceutical manufacturing company), the monitor is a contract research organization, the research doctor, the patient). In addition, triple-blind studies are possible, when neither the doctor, nor the patient, nor those who organize the study and process its data, know the prescribed treatment for a particular patient.

If physicians know which patient is being treated with which agent, they may involuntarily rate treatment based on their preferences or explanations. The use of blind methods increases the reliability of the results of a clinical trial, eliminating the influence of subjective factors. If the patient knows that he is receiving a promising new remedy, then the effect of the treatment may be related to his reassurance, the satisfaction that the most desired treatment possible has been achieved.

Placebo (Latin placere - to like, to be appreciated) means a drug that obviously does not have any healing properties. The Big Encyclopedic Dictionary defines a placebo as “a dosage form containing neutral substances. They are used to study the role of suggestion in the therapeutic effect of any medicinal substance, as a control in the study of the effectiveness of new drugs. drug drug quality test

Negative placebo effects are called nocebos. If the patient knows what side effects the drug has, then in 77% of cases they occur when he takes a placebo. Belief in one or another effect can cause the appearance of side effects. According to the World Medical Association commentary to article 29 of the Declaration of Helsinki, "... the use of a placebo is justified if it does not lead to an increased risk of serious or irreversible damage to health ...", that is, if the patient does not remain without effective treatment.

There is a term "full blind studies" when all parties to the study do not have information about the type of treatment in a particular patient until the analysis of the results is completed.

Randomized controlled trials serve as the standard for the quality of scientific research into treatment efficacy. For the study, patients are first selected from a large number of people with the condition under study. Then these patients are divided randomly into two groups, comparable in terms of the main prognostic signs. Groups are formed randomly (randomization) by using tables of random numbers in which each digit or each combination of digits has an equal selection probability. This means that patients in one group will, on average, have the same characteristics as patients in the other. In addition, prior to randomization, it should be ensured that disease characteristics known to have a strong impact on outcome occur with equal frequency in treatment and control groups. To do this, you must first distribute patients into subgroups with the same prognosis and only then randomize them separately in each subgroup - stratified randomization. The experimental group (treatment group) is undergoing an intervention that is expected to be beneficial. The control group (comparison group) is in exactly the same conditions as the first group, except that its patients do not receive the study intervention.

Currently, new approaches and requirements for biomedical research are clearly defined. The scientific goals of clinical trials in the treatment of a patient and non-clinical biomedical trials in the performance of purely scientific medical research on humans must be justified, clearly stated in a special protocol, and approved by an independent ethical committee.

Experiments involving humans should be based on data obtained from laboratory studies on animals. This provision is already present in the Nuremberg Code. Experiments on animals allow not only to better understand the laws of life and the mechanisms of individual life processes, but also to improve methods for the prevention, diagnosis and treatment of diseases, both in humans and animals. In addition, many human-made substances, such as drugs, food additives, chemicals, need to be tested for biological activity, and it is clear that such tests can only be done on animals, although, ultimately, they are intended to determine the effect on humans.

This raises a number of moral issues, but the general consensus is that intentional cruelty to animals is unacceptable. Humane treatment of animals helps to strengthen the formation of high moral principles in the doctor.

The main principles of the "International Recommendations for Biomedical Research Using Animals", adopted in 1985 by the Council of International Medical Scientific Organizations, boil down to the following preferences and recommendations:

Use the minimum number of animals;

Minimize the inconvenience, suffering and pain caused;

Use sedatives, narcotic and other painkillers.

If, according to the conditions of the experiment, it is required to do without them, then the conclusion of the ethical committee is necessary.

If after the experiment the animal is doomed to suffering, it should be painlessly killed.

From all the arguments for the clinical experiment and against it, first of all, it follows the need to clarify the fundamental question, namely: is the experiment conducted on a person justified, fair? The answer is clear. The need to conduct an experiment on a person is beyond doubt and is recognized by everyone.

Medicine cannot advance without it. Human experiments are helping to develop more effective preventive and curative methods for the human of the future. Of course, experiments on animals bring a lot of value, and you should always start with this. But the final verification of the proposed methods can only be made by human observation. Thus, the question is not whether to conduct an experiment, but how to conduct it, that is, how to obtain the most information during the experiment and observe ethical standards.

Any problem of medical ethics is considered on the basis of fundamental principles:

autonomy;

Awareness of the patient (parents) about the state of his health and the need to obtain consent to medical interventions;

privacy;

Safety for the patient;

Respect for the dignity and value of the life of each patient;

social justice.

Under autonomy is understood as a form of personal freedom in which an individual performs actions in accordance with a decision freely chosen by him.

According to this principle, the adoption of an ethically sound medical decision is based on mutual respect between the doctor and the patient and their active joint participation in this process, which requires competence, awareness patient and voluntariness decision making. The ethical basis of the principle of individual autonomy is the recognition of its independence and the right to self-determination.

Thus, respect for autonomy refers primarily to a person who has the opportunity and the right to dispose of his life and health, up to the conscious refusal of treatment, even if this decision will cost her life. The principle of personal autonomy is closely related to another fundamental principle of bioethics - informed consent.

Medical confidentiality means:

Information about the patient received by a medical worker from the patient or in the course of treatment is not subject to disclosure;

Information about the patient that the medical worker should not tell him (adverse outcome of the disease, diagnosis causing psychological trauma to the patient, etc.).

The purpose of maintaining professional secrecy is to prevent the possible infliction of moral or material damage to the patient. When applying for medical care and receiving it, the patient has the right to maintain medical secrecy. Medical confidentiality must be preserved in any case. Disclosure of information constituting a medical secret by persons to whom they became known in the course of training, performance of professional, official and other duties is prohibited.

The citizen must be confirmed the guarantee of the confidentiality of the information transmitted by him. With the consent of the patient or his legal representative, it is allowed to transfer information constituting a medical secret to other citizens, including officials, in the interests of examining and treating the patient, for conducting scientific research, etc.

If in ancient times and even in times closer to us, the observance of medical secrecy was absolute in relation to everything that was made known to the doctor, at present, moral and legal deviations from the observance of the rules of medical secrecy have multiplied. Deontology and medical law state the limitations of this secret, caused by social necessity.

Representation of information constituting a medical secret without the consent of a citizen is allowed:

For the purpose of examination and treatment of a citizen who, due to his condition, is unable to express his will:

At the request of the bodies of inquiry and investigation, the prosecutor's office and the court in connection with the investigation or trial;

In the case of assistance to a minor under the age of 15 - to inform his parents;

If there are grounds for believing that harm to the health of a citizen was caused as a result of unlawful measures.

Persons who, in accordance with the established procedure, are provided with information constituting a medical secret, bear disciplinary, administrative or criminal liability for the disclosure of medical secrets.

The first duty of every healthcare worker no harm, damage to health patient. Neglect of this duty, depending on the damage to the health of the patient, may become the basis for bringing the medical worker to legal liability.

iatrogeny (Greek yatros- doctor and genia - arise)- a disease caused by undesirable or adverse effects of medical interventions and leading to various violations of body functions, restrictions on habitual activities, disability or death. Doctors have known for a long time that the inept handling of the word or the prescription of some drugs can harm the patient. The term "iatrogenic" became widely known in medicine thanks to the article "The Doctor as the Cause of Mental Illness" (1925, O. Bumke).

Respect for the human dignity of the patient duty of every doctor.

When communicating with a patient, the doctor should not forget about the following rules:

Always listen carefully to the patient by asking him a question;

Always be sure to wait for a response;

Express your thoughts clearly, simply, intelligibly.

Showing arrogance, disdainful or humiliating treatment of the patient is not acceptable.

All people, including patients, regardless of their social status, mental and physical condition and behavior, have equal rights to recognize and respect one's own dignity. In biomedical practice, this principle covers a wider range of situations than the principle autonomy, which presupposes the conscious capacity and independence of the individual. Respect for human dignity is connected, but not only with the presence of a sense and consciousness of one's dignity, which are manifested in the individual's inner confidence in one's own value, resistance to attempts to encroach on one's individuality and independence, self-respect (they may not exist).

The principle of respect for dignity also applies to such situations when a person is not able to express his will, when, due to his physical or mental disorder, he is completely incapable of autonomous actions, when one has to talk not even about a human personality, but about a human being. We are talking about such situations as a vegetative existence, severe forms of a geriatric condition, experiments with a human embryo, etc.

A special role in the system of bioethical principles is played in this regard by the principles integrity And vulnerabilities put forward by European bioethicists. These principles are directly related to respect for the dignity of the individual and affect both the physical and mental aspects of the life of the individual.

Integrity- this is what ensures the identity of the individual to himself, his self-identification, and therefore should not be manipulated or destroyed. It is associated with the "life history" of the individual, which is created by the memory of the most important events of one's own life and the interpretation of life experience. In other words, the integrity of a person is its uniqueness, individuality and uniqueness.

Unfortunately, some medical interventions that have a good goal of restoring a person's health, improving his condition, are often associated with a violation of integrity. The need to protect the psychophysical integrity of a person, to minimize its violations, today requires the development of ethical and legal norms related, in particular, to genetic manipulations and interventions in the genetic structure of an individual, to the problem of using parts of the human body - organs and tissues, etc.

Vulnerability as a principle of bioethics should be understood in two senses. Firstly, as a characteristic of any living being (not necessarily human), each individual life, finite and fragile by its nature. In this sense, vulnerability as a general characteristic of life can have a broader than bioethical meaning: it can become a link between socially and morally alienated people in society, uniting them in search of overcoming their own vulnerability. To a certain extent, all progress in the field of medicine and biology can be seen as a fight against human vulnerability, caused by the desire to minimize or "push" it.

At the same time, vulnerability - including mortality and finiteness - is optimistically regarded as a certain circumstance that can and must be overcome. True, there is a danger here of depriving a person of the experience of pain and suffering, which are very significant in our perception of reality. The second understanding of vulnerability, in a narrower sense, refers to certain human groups and populations (the poor, the semi-literate, children, prisoners, the disabled, etc.). Here, this principle underlies special care, responsibility, sympathy for another, weaker and more dependent, and requires for its implementation the observance of another principle of bioethics - the principle of justice.

Justice— the principle that involves the implementation of a social program, in accordance with which equal access is provided for all strata and groups of the population to public goods, including the receipt of biomedical services, the availability of pharmacological agents necessary for maintaining health, protection during biomedical research of the most more vulnerable segments of the population. According to the principle of justice, the benefit to the patient must always exceed the scientific or public interest.

Thus, the considered fundamental principles of bioethics do not exhaust the methodological basis of moral regulation in biomedicine. Its basic foundations also include highest moral values acting as a form of manifestation and addition of bioethical principles (Good and Evil, Suffering and Compassion, Freedom and Responsibility, Duty and Conscience, Honor and Dignity).

Ethical rules and legal issues of doctor-patient relationship

Over the years, the medical community has developed a number of ethical criteria and rules that must be followed by a doctor when providing medical care to a patient.

Ethical rules: fairness rule, truthfulness rule, confidentiality rule, and informed consent rule.

The rule of justice is revealed quite fully and at the same time is compressed in the Oath of the Doctor of the Republic of Belarus. Article 60 of the “Fundamentals of the Legislation of the Russian Federation on the Protection of the Health of Citizens” says that the doctor swears “... to treat the patient carefully and carefully, to act exclusively in his interests, regardless of gender, race, nationality, language, origin, property and official position, place of residence, attitude to religion, beliefs, membership in public associations, as well as other circumstances.

True information about the real state of the patient's health is an indispensable condition for obtaining the patient's consent to medical intervention. The right of citizens to information about their state of health is proclaimed in Article 31 of the Fundamentals of the Legislation of the Russian Federation on the Protection of the Health of Citizens (dated July 22, 1993): about the results of the examination, the presence of the disease, its diagnosis and prognosis, the methods of treatment, the risks associated with them, possible options for medical intervention, their consequences and the results of the treatment."

Previously, the approach more often dominated was to hide the truth about an incurable disease, especially a cancer patient. Now more and more doctors recognize the patient as an equal partner and tell the truth. Disputes and discussions are conducted on the issue of “the right of the patient to the truth about the latest diagnosis”. In our opinion, the moral atmosphere that develops around the patient in a situation of lies humiliates both the patient and the doctor and negatively affects the patient's condition. “Truth remains the basic condition under which a moral act can be considered objectively positive, so lies should be avoided, often elevated to a systematic principle by relatives and medical personnel.

The literature confirms that when the truth is revealed to the patient at the right time and he accepts it, it has a positive psychological and spiritual effect, both on the patient himself and on his loved ones. (Sgrechcha Elio, Tambone Victor. Bioethics. Textbook. M., 2002, p.362-363). Of course, one must learn how to tell the truth, how to prepare the patient for this, so as not to harm him. “Although lying cannot be accepted as a line of conduct, and the communication of the truth remains a goal to be striven for, it should, however, be remembered that this truth must be proportionate to the ability of a person in order to properly receive it. ... You should never completely deny the patient hope, since in medicine there are really no absolutely accurate predictions ”(ibid.).

There are other situations where the fairness rule must be satisfied. For example, within the medical team, information about the patient's condition should also be available. Ethical standards prescribe, in the interests of the patient, not only the attending physician, but also all specialists to know the truth about the patient's state of health.

The rule of truthfulness applies to the patient himself. Concealment of the truth about the disease itself is unacceptable, especially if it is a sexually transmitted disease. Hiding the truth in AIDS, syphilis and similar diseases is a threat to the spread of infection in society.

In clinical trials of drugs, the question of hiding the truth from the patient when using a pacifier tablet - a placebo as a control - has arisen, but even in such cases, a positive result was sometimes observed. Many experts view the issue of placebo more as a research method, not considering it in the context of the ethical rule of truthfulness.

And, finally, truthful information about the patient for students of medical institutions should be available with the consent of the patient or his authorized representative.

The truthfulness rule is closely related to the issue of confidentiality. The Confidentiality Rule states: "Health information may not be shared with third parties without the consent of the patient." The guarantee of confidentiality is proclaimed in the Fundamentals of the Legislation of the Russian Federation on the Protection of the Health of Citizens. Article 61 on medical secrecy states: “Information about the fact of applying for medical care, the state of health of a citizen, the diagnosis of his disease and other information obtained during his examination and treatment constitutes a medical secret. The citizen must be confirmed the guarantee of the confidentiality of the information transmitted by him.

Medical secrecy protects the patient's private life, his social status and economic interests. It is of paramount importance in mental, malignant, venereal and other diseases. Confidentiality of medical information protects the patient's right to autonomy, i.e. the right to be in charge of one's own life.

Maintaining medical secrecy promotes truthfulness and frankness in the relationship between the doctor and the patient, protects the image of the doctor himself and strengthens the patient's trust in medical workers. On the one hand, confidentiality is a rule of conduct for a doctor. On the other hand, the doctor must be well aware of situations where the preservation of medical secrecy is not good for the patient or poses a threat to others. Article 61 on medical secrecy of the Fundamentals of the Legislation of the Russian Federation on the Protection of the Health of Citizens states the following:

“With the consent of a citizen or his legal representative, it is allowed to transfer information constituting a medical secret to other citizens, including officials, in the interests of examining and treating a patient, for conducting scientific research, publishing in scientific literature, using this information in the educational process and in other purposes.

Submission of information constituting a medical secret without the consent of a citizen or his legal representative is allowed:

For the purpose of examination and treatment of a citizen who, due to his condition, is unable to express his will;

With the threat of the spread of infectious diseases, mass poisoning and lesions;

At the request of the bodies of inquiry and investigation, the prosecutor and the court in connection with the investigation or trial;

In the case of assistance to a minor under the age of 15 to inform his parents or legal representatives;

If there are grounds for believing that harm to the health of a citizen was caused as a result of unlawful actions.

The rights of patients in medical interventions are protected not only by the rule of truthfulness and the rule of confidentiality, but also by the rule of voluntary informed consent. According to this rule, any intervention, including when conducting experiments on humans, must include the voluntary consent of the patient. In turn, the doctor must inform the patient about the goals, methods, side effects, possible risks, duration and expected results of the study. For the first time, the rule of "voluntary consent" is formulated in the Nuremberg Code (1947) - the first "Code of rules on conducting experiments on humans."

Then the principle of “free consent” began to be taken into account in the United States in litigation for damages for negligent treatment. The term “informed consent” has taken root in Europe 10 years later. In practice, indeed, a situation of natural inequality develops between the doctor and the patient. The patient, not possessing special medical knowledge, trusts the doctor with his life. But the doctor himself is not immune from medical errors. The legal protection of the patient eliminates this inequality, and the principle of voluntary informed consent establishes new norms for the relationship between the doctor and the patient.

In Russian legislation, this is reflected in the Constitution of the Russian Federation, Article 21 “... No one can be subjected to medical, scientific or other tests without voluntary consent”, as well as in the “Fundamentals of the Legislation of the Russian Federation on protecting the health of citizens in Art. 32. Consent to medical intervention. “A necessary precondition for medical intervention is the informed voluntary consent of the citizen”, in Art. 31.

The right of citizens to information about the state of health is also in Article 43, which specifies the procedure for obtaining the written consent of a citizen. The concept of voluntary informed consent establishes the duty of the doctor to inform the patient, as well as respect the patient's privacy, be truthful and keep medical secrets on the one hand, but on the other hand, this principle obliges the doctor to accept the patient's subjective decision for execution. The incompetence of the patient can render this model of doctor-patient relationship sterile and even harmful to the patient himself, as well as cause alienation between patient and doctor.

A positive feature of voluntary informed consent is that it is aimed at protecting the patient from the experimental and testing intentions of the doctor and researcher, at reducing the risk of causing moral or material damage. At the same time, in a situation where harm has occurred, although a voluntary informed consent was issued between the doctor and the patient, it is a form of protection for the doctor, weakening the legal position of the patient.

“In this regard, it must be emphasized that modern medicine is to a large extent the medicine of research, experiments and clinical trials conducted on animals and humans. Almost a century ago, in Versaev's "Doctor's Notes", the problems of ethical and humane treatment of subjects - participants in medical experiments were raised in extremely sharp forms.

Since then, both medicine itself and the understanding of its ethical problems have come a long way. Today, the ethics of biomedical experimentation is by no means just a wish list. There are norms for conducting such experiments that have been developed and tested by practice, as well as structures and mechanisms that make it possible to strictly control the observance of these norms.