Clinical trials of medicines for medical use as a stage of supply of medicines: concept, participants, features and legislative governance

CTs represent the most important stage in the process of the medicinal supply, as they are designed to ensure the quality, safety and efficacy of a new drug. As early as 250 years ago, the great philosopher Voltaire wrote: "Doctors distribute the medicines that they know so little to cure the diseases that they know even less to those people about whom they know nothing."[248] The sarcasm inherent in the author of this statement brightly reflects one of the global problems that arise in the treatment of a patient with the use of drug therapy, namely: what is the mechanism of action of the drug, how effective it will be in treating this disease, is it safe for the human organism in general.

Fidning the answers to these questions is the main goal of the CT, designed to ensure that the new medicine has been thoroughly studied by pharmacologists, and its safety and

efficacy are indeed clinically proven.

Since the middle of the twentieth century, CTs have become widespread in the US and European countries. In the Russian Federation, the process of conducting CTs (especially international multicentric CTs) began much later, but every year their number is steadily growing. So, according to the statistics in 2014, the Ministry of Health of the Russian Federation issued 750 permits for all types of CTs. The CT sponsors allowed to be held in Russia in 2014 were companies from 35 countries, while Russian producers took over the leading postitions with their 345 CTs. 30 In 2015, the Ministry of Health issued 804 permits for clinical trials (7.2% more than in 2014), including 289 permits for international multicenter studies. In 2015 the local research sector of Russian sponsors grew by 17.6%, while the research of foreign sponsors decreased by 16.1% compared to the previous year. During the first half of 2016, the Ministry of Health of Russia issued 450 CT permits, which already constitutes 29.7% more than in the same period of 2015.

At the same time, the number of permits for international multicenter clinical trials (IMCTs), as compared with 2015, practically did not change, the increase was mainly provided due to the number of approved local studies.31

Thus, it can be stated with certainty that at present Russia is fully included in the process of conducting international multicenter studies carried out by both foreign pharmaceutical manufacturers and Russian ones, and the share of the latter in the overall amount of CTs is steadily increasing, which suggests that the measures aimed at achieving medicinal security of the Russian Federation are quite functionable.

When deciding to develop a new drug and hold a CT, the main criterion is its (drug's) social significance, determined by the demand in the pharmaceutical market for morbidity indicators, prevalence of pathology in the population, etc. In this case, there is a certain algorithm for the development of medicines. As

Professor Yu.B. Belousov stated, when a new medicine is developed, the sequence of research is always observed: from cells and tissues to animals, from animals to healthy volunteers, from a small number of healthy volunteers to patients.32 The chemical formula is repeatedly tested, the research program is being developed, its budget is planned, after that the medicinal product is registered and displayed on the basis of the received data on the physiology of a particular pathological process. On average, about 10-12 years pass from the idea to the release of a drug. The process of conducting CT can be divided into three consecutive stages. The first stage (preliminary) is planning and preparation for the CT, which includes the development of the necessary documents. The second stage (main stage) is the CT itself, and the third stage (final stage), which involves processing of the data obtained as a result of the CT, the preparation of a study report, which is a prerequisite for the registration of a new drug.

The cost of the entire process of creating a new drug from the discovery of the molecule till the registration of the drug costs an average of 900 million US Dollars, with more than half of the costs being discharged on the stage of a CT.

In a thesis devoted to the analysis of the legal nature of the contract for the conduct of clinical trials of medicines, N.G. Balibardina opined that the conduct of the CT is quite notable for the heterogeneity of underpinning legal relations, and therefore, it can not be attributed fully to either medical activity, since it does not coincide with it as to its tasks, or scientific activity, since it is carried out not by scientists, but by medical workers. This type of work should be attributed simultaneously to a variety of medical and pharmaceutical activities due to special subject composition, target orientation, as well as the nature of interference in the corporal sphere of an individual. At the same time, the goals of various CT participants are different, they include acquisition of new scientific knowledge, benefits to the society through by reducing the morbidity rate, and the

benefits directly to the patient who participating in such CTs.[249] This approach deserves all possible support, since the heterogeneity of the interests of the participants in the CT leaves an imprint on the specifics of the studied legal relationships under.

In accordance with Art. 4 of the Law on the circulation of medicinal products, CT is "the study of the diagnostic, therapeutic, prophylactic, pharmacological properties of the medicine in the process of its use by humans or animals, including absorption, distribution, alteration and excretion, by applying scientific methods of evaluation in order to obtain evidence of the safety, quality and effectiveness of the medicinal product, data on undesirable reactions of the organism of a human or an animal as to the use of the medicinal product and the effect of its interaction with other medicines and (or) food or nutrition." The definition of CT given in the law by virtue of the indication in it of both human and animal subjects of research is common to the clinical study of the medicinal product for medical use and for the clinical study of the medicinal product for veterinary use.

It is important to note that this paper concentrates at studying the features of legal governance of the CTs with human subjects. In this context, it is necessary to turn to a special normative legal act regulating the process of conducting CT in the Russian Federation - the National Standard of the Russian Federation "Good Clinical Practice" (GCP) GOST R 52379-2005, approved by Order of the Federal Agency for Technical Settlement and Metrology dated September 27, 2005 No. 232-st. (hereinafter - the Standard).[250] So, in accordance with Art. 1.18 of the Standard, a clinical trial/study is any study conducted with a human subject as a subject to detect or confirm the clinical and/or pharmacological effects of the products being tested and/or to identify unwanted reactions to the products tested and/or to examine their absorption, distribution, metabolism and isolation in order to assess their safety and/or efficacy.[251] What is important is the fact that the Standard is identical to the corresponding international regulation governing the CTs[252], the provisions of which are applied by the entire international medical community. At the same time, in international documents, the notion of "subject" in CT is applied in the narrow sense, i.e. only as a "subject of research", that is, the person subject of an experiment, in other words, it is the patient or the examinee. However, in the legal relations that arise during the CT, there are also other actors that are involved, which will be together referred to in this paper as the CT participants.

Based on the legislation of the Russian Federation in the field of CT, it is possible to establish the following circle of participants.

The first participant of the CT and the initiator thereof is the Organizer or Sponsor of the research. The concept of the Sponsor is defined in clause 1.55 of the Standard, as an individual or legal entity that initiates a clinical trial and is responsible for its organization and/or financing.

As a rule, such a person is a pharmaceutical company, a developer of a new medicinal product.[253] In this connection, it is necessary to specify that the Law on the circulation of medicines somewhat differently identifies the initiator of the study, so in part 3 of Article 39 it is stated that the organization of the CT may be carried out by: the developer of the medicinal product or his authorized person; organizations of higher education, organizations of additional vocational education; research organization.[254] At the same time, in practice the CT is almost always initiated and funded by the developer of the medicinal product, therefore, in order to apply a unified approach, the term "Research Sponsor" will be used in this paper. To conduct the CT, it must obtain permission from the authorized executive body and enter into a

contract with a medical entity accredited to conduct CT in the manner prescribed in the law.

Accordingly, the second CT participant is the Medical Entity, defined in section 1.35 of the Standard as an organization (medical): any organization, regardless of its organizational and legal form, or a medical or stomatological department, where clinical trial is conducted. The Law on the circulation of medicinal products stipulates a mandatory requirement for the Medical Entity that conducts CT - it must be accredited by an authorized federal executive body in the manner established by the government of the Russian Federation. Such an federal executive body is the Ministry of Health of the Russian Federation, which carries out accreditation of medical entity for the conduct of CT and maintains a register of such entities.[255]

The third CT participant is a physician-scientist, who, in accordance with section 1.13 of the Standard is called the researcher and is defined as an individual responsible for carrying out a clinical trial at the research center. In the case when the research is conducted in a research center by a group of persons, the researcher (chief researcher) is the head of the group.

More detailed requirements for the researcher are set out in Article 40 of the Law on the circulation of medicinal products: "The head of a medical entity that conducts a clinical trial of a medicinal product for medical use appoints a researcher responsible for conducting such a study and having a medical specialty corresponding to the ongoing clinical trial of the medicinal product, with working experience of no less than three years that offers candidates for appointment as his co-investigators from among the doctors of this medical entity."

The fourth CT participant is the subject of the study, who is defined by section 1.58 of the Standard as an individual who participates in a clinical trial in the group taking the product under investigatiom, or as part of a control group.

The subject of the study, who for medical reasons can be brought to a clinical trial of a medicinal product for medical use, is named in the Law on the circulation of medicinal products as a patient, because during the CT he receives medical assistance. However, in international documents and in the legal literature, the term "subject" is often used instead of the terms mentioned. Taking into account the established practice of use in international and Russian normative acts, the terms "subject of research", "subject of experiment", "patient", "subject" will be used as having the same meaning .

For the purposes of this paper, it is important to point out the existence of a conflict, which is a priori embedded in the ideology of CT. As the academists note, the very nature of the relationship between the researcher and the subject is such that their goals are essentially different: if the former the most important is getting new knowledge, then for the latter, of course, it is to get medical assistance and to improve health. This, of course, is not about cruelty, malice or indifference of the person who conducts the experiment, but about an objectively existing conflict of interests that creates a number of legal, ethical and deontological questions: are clinical trials permissible in humans, and if so, what should be the restrictions and conditions for their conduct? How to reduce the possible risk to the patient, to ensure the conditions of confidentiality? How to avoid possible abuses in research? How correctly to organize research taking into account the features of the legislation and social conditions of different countries, and also to observe and protect the rights of persons taking part in them?[256] Thus, there are cases when the researchers continued a patient's participation in the experiment, despite the deterioration of his health, in order to obtain as much scientific information as possible, which unquestionably conflicted with their responsibility for the patient, because they acted as doctors at the same time. Before them there was a question as to the necessity to stop the research that does not help the patient or leads to significant negative effects indequate to the benefits obtained. At the same time, it is important to single out one more issue related to the conflict in the CT, concerning the legitimacy of receiving the physician-scientist's remuneration for his work on the trial. The legal aspects of this subject will be discussed in detail in the third chapter of this paper.

In addition, there is a certain conflict of interest in the relationship between the research sponsor and the patient, in fact, according to professionals, in terms of profitability, the market of medicines is on the third place after the sale of weapons and drugs, and, therefore, pharmaceutical companies are always interested in a quick release and highest sales of the new drugs. Their interest does not coincide with the interest of the subject of the study, and therefore the task of the regulatory bodies is to bring those interests in line, making it possible to obtain profit only if the company has produced a really effective and safe drug and its test was conducted in accordance with a competently and ethically drafted Protocol (research program)[257].

Another and no less important feature of the CT, is the increased riskiness of the process, exceeding even repeatedly the insecurity of medical activity, which many experts in the field of medical law are classed as potentially dangerous. So, M.I. Litovkina points out that since the medicines that are used in CTs have not undergone the state registration procedure, they do not meet the safety requirements, they have harmful properties corresponding to the characteristics of the source of increased danger, which means that carrying out CT implies the harm, and the risk of it is multiplied as compared with any other medical activity.[258] In itself, the main goal of CT, which is to establish the safety and effectiveness of a new medicine, is achieved, among other things, by identifying the negative consequences of its use. That is, the detection of harm, which is the goal of the test, implies the inevitability of this harm. This specificity of the process, consisting in increased risks for the subject, is also evidenced by the fact that Art. 39.1 of the the Law on the circulation of medicinal products establishes the mandatory receipt before the start of the study of a positive ethical review by the Ethics Council. In assessing the ethical validity of the CT, the Ethics Council considers the issues of the correlation between harm and benefit in the study conducted and the possibility of minimizing risks for the subjects of the experiment.

Given the specific features of the CT, based on the Constitution of the Russian Federation, it can be argued that the main principles in any CT should be the principles of priority of the patient's health and life, of prohibition of violation of his rights during CT, and the obligation to provide guarantees and compensation in the event adverse consequences. In addition, compliance with all the above-mentioned principles should, in turn, serve as a protective mechanism against erroneous assessments and conclusions, and be a guarantee of the reliability of the conducted study. Currently, the legislation is aimed specifically at minimizing the risks and consequences for health and life of the patient in the conduct of CT.

However, in spite of the high likelihood that the life and health of the patient may be harmed, one should not forget about the physician-scientist who conducts it, as he is responsible for the health and life of the patient. It can be said that causing harm to the life and health of a patient due to the use of an experimental medicine is also the professional risk of the physician-scientist who is treating with an unexplored drug and should take into account the unpredictability and even a possible danger of its use. At the same time, it should be noted that experts, analyzing the correlation of the rights of patients and medical workers, suggest that the most undeveloped, both legislative and scientific, remains the issue of protecting the rights of health workers themselves.[259]

Concluding on the point of this peculiarity of the CT process associated with the risky nature of the medical experiment conducted with the participation of a human as its subject, and taking into account the objectives of this paper, we note that the risks in CT are understood as the risks associated with the effect of an unexplored drug on the human organism. This position fully corresponds to the definition of risk, as a legal category, enshrined in the National Standard of the Russian Federation in the field of risk management[260], where it is indicated that the risk is a consequence of the impact of uncertainty on the achievement of the goal, a deviation from the expected result or event (positive and /or negative). It should be noted that the aforementioned risks are social, because, on the one hand, they are associated with the possibility of worsening the patient's health up to a lethal outcome, and, on the other hand, they are related to the professional responsibility of the doctor for the welfare of the subject of the experiment.

However, when studying the legal and social nature of CT, it is important not to lose sight of the specific focus of this activity, namely: the creation of an effective and safe medicinal product for an indefinite circle of consumers. In other words, the social benefit to which the CT process serves is intended in favor of the entire population of the country, which will be provided with medicines with proven safety and effectiveness. Consequently, due to the direct interest of potential medicine consumers in conducting research, there is a reason to treat them as a kind of a "collective subject" of CT relations, who does not directly participate in the process, but is indirectly involved in it by its dependence on the results of CT.

In this regard, the process of the emergence and development of legislative regulation of CT is very significant, since the need for legal protection from dangerous and inferior medicines of an unlimited range of potential consumers - was foremost, which led to the need to regulate the requirement for a preliminary trial of a medicine before it is released to the market. It can be said that, first of all, the fundamental principle of CT was formulated, which is, in fact, its legal and social meaning: the principle of mandatory preliminary trial of the drug in order to establish its safety and effectiveness. And only decades later, legal norms were introduced (at the international level) regulating participation of the patient in CT as a subject of the experiment and establishing legal protection for him. That is, the movement of the legal matter in this context has occurred from the general to the specific, by the method of deduction, which involves the transition from general premises to specific conclusions.

Thus, the world's first law obliging manufacturers of medicines to conduct research on their safety, was the US Food and Drug Administration Act (Federal Food, Drugs and Cosmetics Act)[261], which vested an American regulatory body, the FDA (Food and Drug Administration)[262] with the uthority to issue permits for the sale and safety control of food, cosmetic and medical products. This law has marked the beginning of the normative consolidation of the obligation to conduct a preliminary trial of medicinal products before releasing them for the use by an unlimited number of persons. At the same time, the ethical and legal aspects related to the experimentation on people remained outside the scope of the regulation of the above law.

Further development of legislation in the field of trials of medicines was a consequence of the events of World War II. The Nuremberg tribunal has considered US v. Karl Brandt et al., recorded in history as the "Doctor's trial".[263] The tribunal examined the legitimacy of medical experiments conducted over the prisoners of concentration camps. The purpose of such experiments was to study the following matters: human body's response to various factors, such as large altitudes and rarified air; mass infection with infectious diseases; wound infections; bones and muscles' ability for regeneration; speed and nature of the effect of poisons on the human body; methods of sterilization of humans, etc. The lawyers' defense of the suspects was based on the absence of statutory principles and rules that would divide the experiments on humans into those that are legal and those that are illegal, and therefore it was not possible to give a legal qualification to the act committed and determine which rule of law was violated. Thus, the world community faced the fact that the norms of universal morality are not sufficient as a public regulator of the corresponding social relations without fixing them as legal norms.

In order to establish the criteria for determining an unlawful nature of the experiments conducted by the Nazis, American lawyers Leo Alexander and Andrew Ivey, together with the Tribunal, have developed a Memorandum, which set out ten principles for conducting medical trials involving humans. On August 19, 1947, together with the judgment in the Doctor's trial, the Nuremberg Code was adopted. [264] This was the first international document containing a list of ethical and legal principles for conducting trials on humans. [265]

Thus, the Nazi crimes over the prisoners of concentration camps were have provided a clear proof that it was necessary to protect the rights of the subjects during medical experiments, as well as that it is impossible to regulating such relations by the norms of universal morality. The Nuremberg Code was a precedential act, which fixed in legal form the basic provisions that correspond to the requirements of morality, ethics, guaranteeing observance of the rights of the subject of a medical experiment. Among these are the following principles:

- patient's awareness[266], that for the first time ever has established the

voluntary participation of a person in a medical experiment (formulated as voluntary consent) and inadmissibility of coercion of the subject to give informed consent, the right to refuse to participate in an experiment at any stage of its conduct, and the guarantee of treatment and medical care in case if the patient elects to get out of the trial;

- trial based on the data obtained in laboratory studies on animals, knowledge of the history of the development of the disease or other problems studied, its conduct should be organized in such a way that the expected results could justify the very fact of its conduct;

- absense of any unnecessary physical and mental suffering and damage, which should be minimized (development of ways to minimize risks);

- prohibition of the trial to be conducted, if there are "a priori" reasons to assume the likelihood that the subject dies or incurs disabling damage, which implies an assessment of the balance of benefit and harm in the study, as well as an assessment of the risks for the subject of the experiment.

The provisions enshrined in the Nuremberg Code were of fundamental importance for the development of both legislation and ethical standards for conducting CT throughout the world, which was noted by S.V. Bakhin. In his work he calls the Nuremberg Code a unique international document, noting that when analyzing the legal nature of the code, it seems obvious that it is not an international legal document, but is an integral part of the sentence rendered by a national court in a specific case. However, the Nuremberg Code has not lost its meaning and serves as a vivid example of the influence of national judgments on international rulemaking.[267]

In accordance with the provisions of the Nuremberg Code, the Helsinki Declaration on the Principles of Research with Human Participants was adopted in 1964 in Helsinki at the 18th Assembly of the International Non-Governmental Organization, the World Medical Association (WMA)[268] (hereinafter - the Declaration). The provisions of the Declaration were repeatedly revised, and the most recent revision took place during the 52nd WMA General Assembly in Edinburgh (Scotland) in October 2000.

The Declaration detailed the provisions of the Nuremberg Code governing medical experiments on humans. To date, it is a comprehensive legal act that defines the criteria for the legitimacy of medical experiments, and is also a practical tool for reseaching physicians, in this connection, much attention is paid to the prevalence of the interests of subjects of the experiment over the interests of science, the importance of developing criteria for scientific validity and mandatory documentary fixing of all of the features of the experiment, as well as the requirements for researchers, their qualifications and responsibilities.

It is important to pay attention to the fact that the norms of the Declaration have an advisory character, while the specific rights, duties and liabilities of the participants in the study should be fixed in the national legal systems of the participating countries. Thus, taking into account the advisory nature of this document, the Declaration can be attributed to the so-called "soft law" documents, the prescriptions of which can have a binding political rather than legal nature.[269] However, since the Declaration was recognized as mandatory for the use in the countries participating in the World Medical Association, the integration of its provisions reflected in the national legal systems of these states, including the Russian Federation, making them mandatory.

After the adoption of the above Declaration in 1964 by the WMA, the UN General Assembly has adopted the International Covenant on Civil and Political Rights on December 16, 1966,[270] which established a ban on conducting medical experiments on humans without their consent. Article 7 of the Covenant provides: "No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment. In particular, no one shall be subjected without his free consent to medical or scientific experimentation."[271]. Thus, the Covenant has recognized that the above activities cannot be permitted.

The next normative document in the field of international legal regulation of medical research with human participation is the vention for the Protection of Human Rights and Dignity of the Human Being With Regard to the Application of Biology and Medicine (the Convention on Human Rights in Biomedicine)[272], adopted by the Parliamentary Assembly of the Council of Europe in April 1997. Russia joined the Council of Europe in February 1996, but so far it has not ratified the Convention for legal and technical reasons. Nevertheless, the basic legal meaning of this normative instrument is taken into account by the national legislation of Russia. The Convention has proclaimed as its basic principles the importance of measures aimed at protecting human dignity and basic human rights and freedoms in connection with the use of the achievements of biology and medicine, as well as the necessity of professional requirements and standards in carrying out this activity. In addition, the Convention has enshrined the following important provisions: firstly, States Parties should provide appropriate legal protection against the violations of the rights and principles enshrined in the Convention (Article 23); secondly, a person that incurred the damage has the right to a fair compensation, the conditions and procedures of which should be provided for by law (Article 24); thirdly, States Parties must provide appropriate

sanctions for violations of the provisions of the Convention (Article 25).[273]

In this regard, it should be noted that the Convention has not only embodied the principles of conducting experimentation with human participation, reflected in previous international documents, but also legislated the necessity of the legal protection of patients and mandatory compensation to patients in certain cases, as well as the sanctions for violations set out in the Convention. All these provisions should be developed and implemented in the national jurisdictions of the States Parties to the Convention, taking into account their legal systems.

In 1997, following several conferences around the world aimed at the development of international rules for CTs, the management committee of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical Products for Human Use (ICH) introduced the "International Harmonized Tripartite Rules of the GCP" (ICH GCP)[274], that became effective in the US, the European Union and Japan. This document is a set of standards and regulations determining the conduct of CTs and providing for reliability of the obtained data, ethical and legal protection of the subjects of experiments, confidentiality of information, analysis and generalization of information received.

It can be stated that the provisions of the Nuremberg Code, the Helsinki Declaration, the International Covenant on Civil and Political Rights have reflected in the spirit of the laws of the Russian Federation. So, section 2 of Art. 21 of the Constitution provides: "No one shall be subjected to torture, violence, other cruel or degrading treatment or punishment. No one can be subjected to medical, scientific or other experiments without voluntary consent."[275] Thus, the normative document having the highest legal value in the territory of the Russian Federation has imperatively determined the direction of the national legislation in this area towards the basic principles of international law.

Russia has adopted federal laws with enfluence of the provisions of international documents, including those governing the CT processes: FZ No. 323-FZ; Law on the circulation of medicines, as well as certain regulations in their pursuance.

FZ No. 323-FZ in Article 4 calls as one of the basic principles in the sphere of protecting the health of individuals the priority of the patient's interests in medical care. Article 5 establishes that health protection measures should be carried out on the basis of recognition, observance and protection of the rights of individuals and in accordance with generally recognized principles and norms of international law, and in Article 6 it is indicated that the priority of the patient's interests in medical assistance is implemented by observing ethical and moral rules, as well as the respectful and humane attitude of medical workers and other employees of the medical entity. A special legal instrument governing the circulation of medicinal products in the Russian Federation is the Law on the circulation of medicines. It should be noted that all the basic principles of international legal acts concerning patients' rights, ethical aspects of CTs, observance of the risk/benefit balance and the inadmissibility of causing harm to the health of patients participating in CTs are fully integrated into its provisions. A quite detailed regulation of CTs is contained in seven articles of Chapter 7 of the Law titled "Clinical trials of medicinal products for medical use, clinical trial contract, rights of patients participating in these trials."[276]

In Russia, the International Harmonized Tripartite Rules of GCP" were adopted as the national standard - OST 42-511-99 "Rules for Conducting Clinical Trials in the Russian Federation"[277] dated December 29, 1998. Later this document became invalid in connection with the implementation of the National Standard of the Russian Federation "Good Clinical Practice" (GCP) GOST R 52379-2005, approved by the order of the Federal Agency for Technical Settlement and Metrology dated September 27, 2005 No. 232-st. (hereinafter - the Standard).[278] Section 4 of Chapter "Details of the standard" provides: "This standard is identical to the International Consolidate Guideline for Good Clinical Practice of the International Conference on the Harmonization of Technical Requirements for the Registration of Pharmaceutical Products for Human Use. When applying this standard, it is recommended to use the corresponding national standards of the Russian Federation instead of reference international standards." Thus, the norms of the international Good Clinical Practice (GCP) are fully reflected in Russian national legislation and implemented in practice. The standard, based on the rules of international law, is not only a confirmation of the integration of the legislation of the Russian Federation concerning CTs in the international legal system, but also serves as a confirmation of the creation of national legislation governing the CTs, taking into account the special features of the Russian Federation.

The processes of CTs is also regulated by Order No. 200n of the Ministry of Health of the Russian Federation dated April 01, 2016 "On Approval of the Rules of Good Clinical Practice"[279] (hereinafter - the Order), which determines the requirements for planning, conducting, documenting and monitoring the CTs. The norms of the above Standard and Order are aimed at protecting the rights, safety and health of the persons participating in the trials, during which it is impossible to exclude the undesirable impact on human health, and also it is necessary to ensure the reliability and accuracy of the information obtained during the trials. Also, the conduct of the CTs is regulated by other regulatory and legal acts, such

as the Resolutions of the Government of the Russian Federation and the Orders of the Ministry of Health of the Russian Federation.

However, the analysis of the laws of the Russian Federation, as well as the practice of its application, allows us to conclude that the existing legal regulation of the CTs does not provide an opportunity to properly control the process of their conduct, as well as apply sanctions for violations. As was noted earlier, international documents are based on the principle of transferring to national jurisdictions the powers to legally enforce protective mechanisms aimed at minimizing the risks for the subjects and determining sanctions for violations during CTs.

In this connection, E.V. Tarasyants points out that the issue of protecting the rights of the subjects are especially interesting. Such protection can be carried out both at the national and international levels, the former being considered as the most effective.[280] After all, the declarative nature of normative documents adopted both at the interstate level and at the level of international nongovernmental organizations is due, first of all, to the specificity of international law, in which precise regulation, especially with regard to social human rights, is possible only at the national level. In addition, the special feature of international legislation on CTs is its emergence as a clearly expressed humanitarian law, which has as its objective, first of all, protection of human rights.

CTs with participation of the patient as a subject, being one of the varieties of medical activity, are regulated by various social regulators, and the problem of effective combination of them is actively discussed by representatives of different fields of science. In the medical community it is a custom to consider the problems of inadequate regulation of CTs from the standpoint of ethics, namely, the professional ethics of a doctor who operates with morality and good faith. At the same time, S.V. Bakhin expressed the opinion that at present there are attempts to replace the development of international legal norms with the

development of specific ethical provisions. The issues of protection of human rights in this area (scientific and technological progress in medicine) cannot be effectively regulated by ethical regulations. What is needed is rather the complementarity between legal and ethical norms, especially since their interdependence can be traced in the existing international law, too.[281] At the same time, representatives of medical science, as a rule, express another point of view under the enfluence of the fundamentals of the medical profession based upon the postulates of the famous Greek physician Hippocrates, who has first introduced and systematized the rules of medical ethics on the basis of medical experience. The main principle introduced by Hippocrates was the principle of unconditional respect for the life of the patient, expressed in two well-known sayings: "Primum non nocere!" (First of all, do not harm!) and "Salus aegroti suprema lex" (Good of the sick is the supreme law!).[282] And whereas for the observance of the law it is enough to follow the rules in due manner, ethics rather require from the doctor to be decent, honest and devoted in the broadest sense of the word, and this can not be regulated by any laws. Ethics impose certain obligations on the doctor, while his patients are provided with certain security guarantees even before they are formulated and protected by the law. There are a number of aspects in the doctor- patient relationship, the legal regulation of which has not yet been developed. In this case, the high ethical principles underlying the actions of the physician participating in the CTs should play a decisive role.[283]

At present, the First National Congress of Physicians of the Russian Federation (Moscow, October 5, 2012) adopted the Code of Professional Ethics of a Physician, which does not have a normative character. This Code established the generally accepted principles of medical ethics in the Russian Federation, which the members of the medical community, including those conducting CTs, undertake to follow. Thus, Article 50 of the above Code provides: "A physician engaged in research activities should not use his scientific knowledge to the detriment of the health and safety of the patient or society. The interests of science and society cannot prevail over the interests of a human", while Article 51 provides: "When planning an experiment involving the patient, a physician must be honest and decent in his actions and compare the degree of risk of causing damage to the patient and the possibility of achieving the expected positive result," and in Article 52 it is stated: "Trials and experiments may be conducted only on condition that the patient's voluntary consent is obtained after providing him with full information. The patient has the right to refuse to participate in the research program at any stage thereof."[284]

In addition to ethical and legal norms, representatives of sociological science indicate another type of a regulator in medical activity, i.e. the professional regulators based on the principle of clinical expediency.[285] They base this conclusion on the fact that medicine is developing in accordance with its own internal principles that form various technologies for prevention, diagnosing and treating the diseases as well as various approaches as to the rehabilitation of patients, while new medical achievements often do not receive social approval because of the conservatism of the legal norms lagging behind the success of medical science. In the opinion of sociological scientists, in this case ethical regulation becomes the resolution of this contradiction.

It appears that in this angle of the problem there is an internal contradiction. First. Professional regulators, according to representatives of sociological science, are not social regulators. Second. Speaking about

professional regulators, they actually vague the regulatory nature of such norms, thus resorting (in case of contradictions) to ethical regulation.

But after all, on the basis of the principle of clinical expediency, the doctor, having discrete powers, chooses the most optimal technologies for prevention, diagnosis, treatment of the disease and rehabilitation for a particular patient. Therefore, the professional regulators in question are also social regulators,[286] and if they are, then they should be referred to the norms of law or to the norms of morality (ethical norms) by analyzing the essence of the regulatory mechanisms.[287]

But the reasonable correlation of ethical and legal norms in the regulation of medical activities (and CTs as one of the types of such activities) remains a big problem. Despite the mediation of social relations arising out of the CTs, the numerous legal norms of various areas (the laws of social security, labor, administrative law, civil law), the CT process is carried out in many ways by ethical concepts. Such a situation can hardly be recognized as effective, taking into account the targeted orientation of CTs as a stage of medicinal supply with increased riskiness of its conduct, as well as the specific features of the research process associated with the need to reconcile the interests of participants. These problems will be discussed in the next chapters of this paper.


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Источник: Маценко Елена Игоревна. Социальная защита лиц в клинических исследованиях лекарственных препаратов для медицинского применения. Диссертация на соискание ученой степени кандидата юридических наук. Санкт-Петербург, 2017. 2017

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