Preventive public law mechanisms of social protection of patients

It seems that it will be correct to initially determine the norms of substantive law that carry out a preventive function in the mechanism of the patient's social protection in CT.

First of all, the participation of the subject in CT is not just participation in a scientific experiment. The CT process is the provision to a person of medical care as a set of measures aimed at maintaining and (or) restoring health and including the provision of medical services (Article 2 of Federal Law No. 323-FZ). That is why the subject of such studies is considered by the Russian normative acts as a patient receiving medical care (most often within the framework of the Compulsory Medical Insurance system)^[324] and at the same time testing a new drug.

According to Art. 37 FZ No. 323-FZ, medical assistance is organized and rendered in accordance with the procedures for the provision of medical care that are mandatory for execution in the territory of the Russian Federation by all medical organizations and also on the basis of medical care standards. They (standards and procedures) are the basis for determining insurance coverage in accordance with the basic program of compulsory medical insurance (part 4 of Article 35 of the Federal Law of November 29, 2010 N 326-FZ "On Compulsory Medical Insurance in the Russian Federation")^[325].

Thus, it can be stated that compliance with the rules and standards for the provision of health care is a preventive public law mechanism for the social protection of the patient in the conduct of CT within the framework of social security relations. However, the social risk associated with the impact on the body from an insufficiently studied medicinal product used in the provision of medical care, leaves its imprint on the organization of medical care within the CT. In a more general form than just in respect of CT, such an approach was embodied in the changes made to the Federal Law No.

Such rules of law (for clinical research) are fixed in the main documents regulating the scope of CT, such as the Law on the circulation of medicines, the Standard, the Order. In order to protect the patient from the possible social risk in CT, the legislator quite rigidly regulated virtually the whole process of CT (within the framework of medical care), thereby providing, first, a special (in comparison with usual patients) social protection of the patient and, secondly, obtaining reliable data during CT, which, in turn, should serve as proof of the safety and efficacy of the tested drug. Accordingly, it can be concluded that the measures of preventive protection of the patient in CT are also measures of preventive protection for the entire population of the Russian Federation.

The most complete document, containing detailed rules for conducting CT, is the Standard, which reads: "This standard is identical to the International Consolidated Guideline for Good Clinical Practice of the International Conference on the Harmonization of Technical Requirements for the Registration of Pharmaceutical Products for Human Use. Good clinical practice (Good Clinical Practice; GCP)^[328] is an international ethical and scientific standard for planning and conducting research involving human subjects, as well as documenting and presenting such studies.

- the rights, safety and welfare of the subject of research are of paramount importance and should prevail over the interests of science and society;

- clinical trials should meet scientific requirements and be clearly and thoroughly described in the protocol;

- the clinical trial should be conducted in accordance with the protocol approved (approved) by the Ethics Committee of the organization;

- the responsibility for carrying out the research, for the medical assistance rendered to the subject and for the medical decisions taken are borne by the doctor;

- voluntary informed consent must be obtained from each subject prior to inclusion in the study;

- all information received in the clinical study must be recorded, transmitted and stored in such a way that accuracy and correctness of its provision, interpretation and verification are ensured.

The above provisions are of a preventive nature, since they are aimed at preventing the social risk to which the subject undergoes during a CT. Accordingly, taking into account the above legislative provisions, the following preventive measures of the patient's social protection in CT can be identified: development at the preliminary stage and compliance with the Protocol of the trial; consideration of the Trial Protocol by the Ethics Committee before the start of the CT; receiving from the patient a voluntary informed consent before starting the CT; correct and complete maintenance of the CT documentation.

Considering these measures with account taken to the application of the principle of constancy and continuity of the patient's social protection at all stages of the CT, it is first of all necessary to pay attention to the Trial Protocol, which is the basic document describing the goals, design, methodology, statistical aspects and organization of CT. The protocol is developed and provided by the research sponsor and, being a set of medical and ethical rules, is a legal act for a particular CT, because:

- the right to adopt the Protocol is delegated by the state to the Sponsor of the trial through the norms of binding, which should ensure the objectivity and reliability of the CT (including through the description of the previously obtained data (preclinical) and the rationale for CT);

- the Protocol must be observed accurately by the Medical Entity through an appointed physician-scientist, without deviations (in the event that deviations from the Protocol are admitted, they must be justified in writing);

- improper compliance with the Protocol may have legal consequences for CT participants through the measures of state coercion (the detailed discussion will be provided below);

- contains the rules of commandment designed for an indefinite range of people and an indefinite number of cases concerning: 1) the "inclusion criteria" of the patient in CT - the diseases in which the investigational drug is to be used; 2) the "stop rules" for CT related to the occurrence of serious adverse events for the patient and the "exclusion criteria" for individual patients (the exclusion criteria are descriptions of those diseases or health conditions in which the patient can not be brought to participate in CT, or the case of his participation in CT, during which there was an appropriate state of health, should be excluded from it); 3) the criteria by which the researcher should determine the efficacy and safety of the drug; 4) mandatory procedures for reporting serious adverse events; 5) the availability and accurate maintenance of all research documentation defined by the Protocol, including the patient's primary medical records, including the patient's individual registration card

(IRC).

Thus, the social preventive orientation of mandatory procedures defined by the Protocol is obvious. Their implementation must prevent the onset of social risk for the subject, and in the event that the patient's health deteriorates at all, then the physician-scientist was to withdraw the subject from the CT. It can be said that the legal requirements for conducting CT that are developed and included in the Study Protocol at a preliminary stage, provide documentarily the necessary preventive mechanisms of the patient's social protection.

Also notable, as a social protection mechanism, is the activity of the Ethics Committees that are independent bodies. These committees' purpose is to carry out independent monitoring of the observance of patients' rights, in

accordnace with the Helsinki Declaration.^[330] Such ethical committees can be created at different levels: at the level of the organization, regional, national and international. The legal status, composition, functions and activities of independent ethical committees, as well as other regulatory requirements related to them are determined by national legislation and may vary from country to country. Nevertheless, they must function in accordance with the rules of Good Clinical Practice (GCP). In this connection Yu.B. Belousov draws attention to the fact that in their composition, procedures and mechanism of decision-making, the Ethics Committees should be independent of administrative, managerial, departmental, professional, financial, economic and political influences.^[331]

In Russia, in accordance with the Standard, ^[332] the activities of the Ethics Committee are an mandatory level making CTs legitimate by ensuring the protection of the rights, safety, well-being of patients participating in CTs, that is, the Committee is the guarantor of such protection vis-a-vis the society. The independence of the Ethics Committee, necessary for its protective activity, is ensured by the fact that it is created in the Medical Entity, which is accredited for conducting CT, and consists of medical workers, as well as persons not related to medicine.

Committee, being a body of independent public control, undertakes a whole range of legal preventive measures aimed at the social protection of the patient in CT.

Another important protective measure, which forms the basis of the preventive mechanism of the patient's social protection in CT, is the procedure for voluntary confirmation of the consent of the subjects to participate in a particular study after receiving the information on all the aspects of the study that are relevant to the decision. It is important to inform the patient since that is the principle of voluntary participation of patients in a scientific medical experiment, which is fundamental and enshrined in both international and national legislation. Art. 43 of the Law on the circulation of medicinal products^[333] provides for the rules governing the process of obtainting informed consent, as well as the content of the information to be provided to the patient prior to the start of the trial, which is the basis for the patient's voluntary decision to participate or not to participate in CT. Such information includes: the data on the drug and the main features of the CT thereof; on the safety of the medicinal product, its expected effectiveness and the degree of risk to the patient; the conditions of the patient's participation in CT; as to the purpose or goals and duration of the CT; as to the actions of the patient in the event of unforeseen effects of the drug on his state of health; on the conditions of compulsory insurance of patient's life or health; on the guarantees of confidentiality of patient's participation in CT.

The patient's voluntary consent to participate in the CT is confirmed by his signature (signed by his legal representative), which indicates not only the voluntariness of his participation in the CT, but also the fact that he received a sufficient amount of information so that such consent could be considered as an informed consent. This fact makes it possible to conclude that the patient agrees with those mechanisms for protecting his rights that are defined by the current legislation as minimally necessary. Assessing the institution of the patient's voluntary informed consent to CT in terms of compliance with his constitutional right to health care, Yu.D. Sergeev and M.I. Litovkina note that the right to voluntary informed consent to participate in CT is a way of realizing the right of every person to freedom and personal inviolability, guaranteed by Art. 22 of the Constitution of the Russian Federation, since according to paragraph 2 of Art. 21 no one can be subjected to medical, scientific, or other experiments without his or her voluntary consent.^[334] Among other things, it should be noted that the process of obtaining informed consent is more than just signing a certain form, since the physician-scientist must verbally answer all questions of the patient's interest, provide all the necessary materials so that the patient can better understand what is happening. In cases where the text of the informed consent is changed already during the CT, the patient should be immediately provided with them, and in case of disagreement and non-signing of such amendments he should be withdrawn from the research.^[335] Thus, it appears that the process of informing the patient and signing voluntary consent is an important and necessary legal component of the preventive mechanism of patients' social protection in CT. At the same time, unlike the other preventive measures for the social protection of the patient in CT, the subjects themselves have an active and decisive role in this process.

In the context of this paper, it should be emphasized that some categories of individuals (even when they give voluntary consent) can not be brought to the CT as subjects. They include such categories as orphans, children without parental care, women during pregnancy and breastfeeding, servicemen, law enforcement officers, persons serving sentences in places of deprivation of liberty, as well as in pre-trial detention centers.^[336] Without analyzing this issue in detail, which requires a separate extensive study, it is necessary to state that such a restriction established by the state can also be considered as one of the legal mechanisms for the preventive social protection of patients in CT.

As it was already noted on the pages of this paper, Roszdravnadzor is the state body designed to carry out supervision and control in the field of CT (and, therefore, to actually implement the mechanism of preventive protection of patients). In this regard, for the purposes determined in this paper, we have studied the practice of the CT checks by this body, as well as other materials: citizens' applications in connection with participation in CT, results of the monitoring of the efficacy and safety of drugs that had undergone the CT procedures, etc. It should be noted that while this dissertation was in progress Roszdravnadzor supervisors have denied the author's request for admission to specific materials with reference to the Federal Law "On Personal Data"^[337] dated July 27, 2006 No. 152-FZ and the author was recommended to use the information placed on the official website of Roszdravnadzor. Therefore, within the framework of this dissertation, the author hereof has analyzed and studied the materials of the CT check-ups for the last few years (from 2013 to 2015) that had been disclosed on the official website of the Roszdravnadzor in the section "Summary and analysis of information on the results of planned and unscheduled inspections of subjects carrying out organization of conducting preclinical trials and clinical trials."^[338]

Taking into account the above agrument on the close interrelation of the elements in the preventive public law mechanism of the patient's social protection in CT, the present research uses an approach that allows using the materials of the Roszdravnadzor inspections to assess the effectiveness of

preventive measures for patient protection, and also to determine the effectiveness of the control and supervisory measures themselves that are conducted within the jurisdictional administrative order.

For example, a survey of data showed that in the course of its control and supervision activities Roszdravnadzor verifies the CT process both on the level of the research sponsor and on the level of the medical entities as to the proper documentation: timing of providing information, development of a proper set of documents, etc., and the inspection also covers the work of the physician-scientist and the medical personnel involved in the research, which includes: selection of suitable patients for the study, their proper informing, prescribing the dose of the drug, entering in the CT reports all information provided by the Law on the circulation of medicinal products, as well as by the Standard and the Order. These inspections can be both planned - for the first time or repeatedly to control the execution of previously issued orders - and also unplanned in case of receipt of the information that there is a threat of harm to life and the health of individuals. So, in 2013, 113 inspections were carried out, and the violations of the established requirements for CTs were found in 46 organizations. In 2014, 77 inspections were carried out, violations were found in 26 organizations. In 2015, 101 inspections were carried out, violations were found in 34 organizations. The vast majority of inspections were have been planned ones, but there were 10 cases of inspections in an unscheduled manner due to receipt of the information that there is a threat of harm to life and the health of individuals. During such unscheduled inspections, the information as to the threat to life and health of patients in CT

was not confirmed.¹²³

At the same time, it is important that the vast majority of planned inspections are carried out at a time when the CT itself has been completed and the CT report containing documented research results is submitted to the regulatory body, i.e. the Ministry of Health of the Russian Federation. That is, on the one hand, this mechanism is preventive, on the other it is a subsequent mechanism only revealing the violations already committed against patients and not allowing to prevent and suppress such violations.

Examination of the disclosed inspection materials for the period 20132015 gives grounds to believe that when conducting CT more often there are violations of formal requirements related to documentary support of CT. Such violations have the following formulations established in the acts of Roszdravnadzor: "the sending of reports on the commencement of clinical investigation to an authorized federal executive body that issued a permit to conduct such a trial within a period not exceeding three days from the date of commencement of the study is not ensured"; "An application for the reissuance of an accreditation certificate within the prescribed period is not provided to the accreditation body"; "In the course of the trial, the authorization to conduct a clinical trial and the contract are formalized for different organizations"; "Appointment by order to establish a responsible researcher and co-investigators from among the doctors of a medical organization is not ensured"; "The distribution of responsibilities among the personnel involved in conducting the trial is not documented," and so on.

While granting a legal assessment of these violations admitted by the Medical Entities and their employees - researching physicians during the CT - it should be noted that there is a non-compliance with the regulatory requirements, but it is rather formal and is eliminated by issuing the corresponding orders, instructions or regulations that are either the acts of law enforcement acts or local regulatory enactments of the medical institution. The most significant circumstance is that these violations are not directly related to a causal relationship with possible harm to the life and health of patients. Accordingly, it can be concluded that such formal violations do not affect the implementation of preventive measures for the patient's social protection in CT, although they testify to the insufficient attention of the management of the

Medical Entities to the research process, which entails increased risks and requires careful documenting.

However, the analysis showed that the researchers, who select and inform the patients, conduct all clinical work with them, including prescription of the medicine, diagnostic procedures, collection of analysis materials, maintenance of medical records, and also generalize the data obtained, and, ultimately, prepare a CT report, and thereby do commit a number of very serious violations. Such violations of the rules for CTs indicate that there is insufficient application, and sometimes even in the lack of preventive protection measures for patients, and therefore there is a direct threat to the life and health of the subjects of the experiment.

As it was already established, the most important preventive measure of the patient's social protection is the exact observance of all provisions of the CT Protocol. At the same time, during inspections of Roszdravnadzor for 2013-2015, violations related to deviation (non-compliance) from the CT Protocol were identified in 48 cases. These violations can be differentiated depending on what specific preventive measures were not performed by the researching physicians.

First of all, violations concern the selection of patients in the trials and compliance with inclusion and exclusion criteria. Violations with the following formulations were found out: "the trial included patients who did not meet the inclusion criteria"; "There is no documented confirmation of the inclusion of patients in the trial that meet the inclusion criteria"; "The inclusion of patients in the clinical trial is not ensured, which for medical reasons may participate in the trial." It seems that these disorders are very serious, since testing an experimental drug on patients that do not match the parameters entails both a significant risk to their life and health, as well as the unreliability of the data obtained during such a CT.

The following group includes violations related to the medical records of patients. In total, 41 were identified as such. At the same time, the following formulations were used by the examiners: "the data in the patient's IRC did not match the data of the primary medical documentation"; "Incorrect data transfer from the patient's primary medical documentation to the IRC was allowed"; "The patient's medical records are not properly maintained"; "No corrections are made to the patient's IRC"; "Medical data was entered immediately into the patient's IRC, while at first they were to be entered on the patient's medical record." In addition, during an inspection conducted by Roszdravnadzor, a case of violation of the order of reporting of adverse events in the patient was revealed. Due to the fact that more detailed information on this violation on the official site is not provided, it is not possible to determine what specific consequences occurred for the patient and other persons, and also how this affected the reliability of the CT results.

The analysis of materials of inspections for the studied period showed that violations related to obtaining informed consent from the patient (informational breach) have been committed 15 times. They are reflected in the results of Roszdravnadzor inspections with the following wording: "Informed consent was not corrected (updated) when new important information was received and the patient was not provided with it"; "The patients are not provided with a new form of informed consent"; "Informed consent is not dated by patients"; "The fact of bringing to the patients a new form of informed consent is not registered"; "Informed consent is not dated by the patient and is not signed by the person conducting the explanatory work."

In particular, it is necessary to specify that there were cases of CT conducted without permission from the Ministry of Health of the Russian Federation, even though such activity is absolutely illegal and unacceptable. The results of such CT should be canceled. But due to the closed nature of Roszdravnadzor's information it is not possible to find out what legal consequences have occurred in these cases.

In addition, what also needs special attention is the situation, in which the following violations (the formulations are given directly from the

Inspection Report) were detected as a result of inspection of the CT conducted by a Medical Entity: "The patients did not sign the informed consent; The inclusion of the patients that are based on medical reasons appropriate for the clinical trial is not ensured; Deviations from the protocol of the trial - these deviations are not registered and are not explained; There is no clear documentation; Data in the IRC do not match the data in the primary medical records of patients; Primary medical records of patients are not provided. "¹²⁴

As it follows from the available information, almost everything that could have been done to protect the patient was ignored, and it is also difficult to discuss the reliability of the results of this CT. Thus, it can be stated that the total absence of preventive social protection of patients in this CT, as well as the lack of preventive social protection for an unlimited number of potential consumers of the drug, which underwent the CT with such violations.

Due to the fact that the activity of the Ethics Committee as an independent body of public control was previously identified as a separate measure of the preventive mechanism of the patient's social protection in CT, the work of which is still strictly regulated by regulatory enactments, it is necessary to specify that the inspections conducted by Roszdravnadzor also concern the activities of the Ethics Committees established in the Medical Entities conducting CT. In the course of its inspections, it checks whether the Ethics Committees comply with the requirements of applicable laws and maintain proper documentation of their activities. Thus, during the analyzed period 2013-2015, 291 inspections were carried out, while in 78 cases violations were registered in the activities of the Ethics Committees. The overwhelming majority of violations can also be recognized as formal, not having a significant impact on the degree of social protection of the patient in CT. Such violations are related to incorrect documentation: "Standard Operating Procedures (SOP) of the Ethics Committee are not developed"; "The documents of the Ethics Committee deviate from the Regulations governing its activities". At the same time, there were isolated cases of serious violations of direct duties of such committees, which are, in fact, protective mechanisms on the side of the society, namely: "the consideration of CT documents prior to the commencement of the study is not carried out, and therefore it was initiated without the approval of the Committee "; "Documents are not provided with a frequency that depends on the degree of risk experienced by the subjects, but at least once a year"; "Admission to discussion and voting on the approval of CT of the persons participating in this CT." ¹²⁵ The above formulations indicate that the Ethics Committees have not fulfilled their direct responsibilities to prevent the occurrence of possible social risks associated with the deterioration of health and possibly even the death of the subject in CT, and therefore we must state that the preventive mechanism of social protection in a particular study has not fulfilled its function.

In the context under consideration, it is significant that only in 2015 (unlike the previous audited period), Roszdravnadzor detected violations during the CT in the activities of pharmaceutical companies that are the sponsors of the trials. Thus, the sponsors of the research have revealed 12 violations, some of them are significant affecting both the well-being of the patient in CT and the reliability of the trial. As an example, the following formulations can be cited from the Roszdravnadzor Report: the developer organization did not ensure compliance with the CT Protocol as to assessment of three undesirable phenomena; The organization-developer did not provide insurance for 7 subjects; There are no documents confirming the compliance of samples of the test preparation with normative and technical documentation; The organization-developer did not ensure the quality of CT at all of its stages. Therefore, it can be concluded that the preventive measures taken by this

research sponsor are inadequate, both to protect subjects in CT, and to protect the end user of the drug.

When we evaluate the effectiveness of such inspectioons conducted within the jurisdictional administrative order as an integral part of the preventive public law mechanism of the patient's social protection in CT, it must be stressed once again that these examinations are usually conducted by the Research Sponsors and Medical Entities, when the CT is already completed and the elimination of the identified violations in no way affects the level of protection of the subjects of the experiment, as well as those results of the CT that have been presented to the Ministry of Health of the Russian Federation. In all these cases of violations of the CT Roszravnadzor issued orders to eliminate violations of by a certain deadline, that means purely formal elimination of violations. An important fact is that the legal consequences for the medical entity in the form of bringing to administrative liability, took place only once during the period of the trial. Thus, the analyzed materials state that "... the violation revealed during the previous inspection (a violation related to the storage of the documents on completed clinical trials) was not eliminated by the time of re-inspection", in connection with which the organization was brought to administrative liability based on section 21 Art. 19.5 of the Code of Administrative Offences for failure to comply within the specified period of legal regulations, the decision of the federal executive authority performing functions on control and supervision in the sphere of public health, its territorial body, and had imposed an administrative penalty of a fine.

This situation is due to the fact that in the RF legislation, until recently, there were no special rules on bringing to administrative liability (as well as to other kinds of legal liability) for violations committed during the CT. Therefore, one could be brought to legal liability only under the general rules on non-compliance with the lawful order (decision) of the relevant federal executive body. Only with the entry into force on July 1, 2015 of amendments to the Law on the circulation of medicines,^[339] a rule was introduced to hold accountable for violations committed during the CT. So, point 12 of Art. 40 of this law, the following special rule is formulated: "Violation of the rules of proper clinical practice, falsification of the results of a clinical study of a medicinal product for medical use entail responsibility in accordance with the legislation of the Russian Federation". The general norms are fixed, first, in point 1 of Art. 68 of the Law on the circulation of medicinal products, which states that a violation of the legislation of the Russian Federation in the treatment of medicinal products entails responsibility in accordance with the legislation of the Russian Federation; secondly, in paragraph 2 of Art. 68 of the said law,^[340] where it is determined that for failure to provide information and (or) data provided by this Federal Law, the subjects of circulation of medicinal products are liable in accordance with the legislation of the Russian Federation. Thus, in order to attract to any kind of legal liability, what is applicable is a special rule of this law governing legal relations in the field of CTs as well as general norms that apply to the entire scope of circulation of medicinal products, to which CT also applies.

The legislator has chosen a blanket manner of formulating the rules of the law of liability in CT, in which the element of the rule of law is expressed in the most general form, referring to other normative legal instruments (without specifying a specific norm).^[341] However, up to now neither the Code of Administrative Offenses of the Russian Federation (CoAP of the Russian Federation) nor the Criminal Code of the Russian Federation (the Criminal Code of the Russian Federation) have provided for legal liability for these violations. In other words, the blanket norms of the Law on the circulation of medicines can not be realized, since there are no legal mechanisms for their effect.

In addition, it is noteworthy that Roszdravnadzor - as a federal service, endowed with all the completeness of state power and having the necessary powers in the field of supervision of CT - takes a passive position in the current situation. As practice shows, the only thing taken by such a body is the issuance of orders (usually of a completely formal nature) to eliminate the violations committed during the CT, which was already completed before the inspection. There is no information on the CT's discontinuation (which may be carried out by Roszdravnadzor) in connection with gross violations of the law regarding the rights of the subjects.^[342] In addition, there are no activities that should be carried out in cases where the inspection has shown that the reliability of the information obtained during the CT on the effectiveness and safety of the drug is questionable, and the CT report has already been adopted by the Ministry of Health of the Russian Federation.

Summarizing the data obtained in the course of the empirical study, it should be noted that the preventive social protection of the patient in CT is not at the proper level, and in some cases it is completely absent, which greatly increases the risks for life and health of the subject. We have to state the fact that the analyzed control and supervisory measures revealed insufficiently effective work of the preventive public law mechanisms of the patient's social protection in CT.

In science more than a decade ago, it was suggested that "a person becomes extremely vulnerable to the use of methods of treatment, clinical research ... Society and law were not ready for such a rapid development of medical technology and the degree of interference in the essence of human. Is not only about the moral and ethical aspects of manipulating the human body, but also, first and foremost, the problems of a legal nature that are expressed in the insufficient legal consolidation of both the relations themselves and the legal mechanism In spite of the intensive administrative reform, the creation of a specialized supervisory authority (Roszdravnadzor), effective methods for monitoring CT, and their compliance with the requirements of the law have not yet been found. As a result of imperfect control, no one was brought to justice and judicial practice was not formed in this field, which, perhaps, would motivate the researchers to avoid violations of the law." ^[343]Fully sharing this statement, we can reliably confirm that the situation has not changed in the past decade, there is still a lack of proper legal regulation that allows for effective preventive protection of patients in CT, as well as obtaining reliable information about the study medication, which should serve as a guarantee medicinal safety for the entire population of the country.

Thus, to create an effective preventive public law mechanism for the patient's social protection in CT, which allows timely detection and suppression of serious violations devaluating the protective focus of legislation, it is advisable to carry out a number of measures aimed at improving legal regulation.

First of all, in order to monitor, inspect and supervise CTs by the inspection authorities, it seems reasonable to distinguish between formal, i.e. that are not life-threatening to the CT patients, and significant ones that entail a violation of the patient's rights, and also affect the reliability of the information obtained during the research. This division is justified, as it takes into account the international experience that exists in this issue. So, the regulatory body in the field of CT in the European Union is the European Medicines Agency (EMA),^[344] while in the United States of America it is the FDA (Food and Drug Administration).^[345] These organizations also monitor CTs conducted in Russia, if the trials are international, multicenter, and reports on their implementation are provided to these regulatory bodies in Europe and the United States. Basically, such control is carried out in the course of inspections conducted by Roszdravnadzor of Medical Entities conducting CT. As noted by the Association of Clinical Trial Organizations (ACTO),^[346] which is a non-profit organization that unites legal entities participating in the Russian market of clinical research, the EMA, unlike the US regulatory body, does not maintain an open register of inspections, so to obtaining and analyzing their results to date is impossible. However, given that the EU is currently pursuing a policy of greater openness of CT data to society, this issue will probably be resolved in the foreseeable future in favor of an accessible inspection register. The American regulator is pursuing a more transparent policy with respect to international inspections. So, according to the official website of the FDA,^[347] for the period since the previous review, 7 FDA inspections were conducted in Russia, 4 without comment, and 3 with uncritical comments. In total, since 1995, when the first FDA inspection was conducted in Russia, up to July 2014, 99 inspections were conducted in Russian research centers. At the same time, in the reports on inspections conducted, the FDA uses the following terms for and classification of violations: NAI (No Action Indicated) - the result indicating no remarks, out of 99 inspections of CTs 65 received this comment; VAI (Voluntary Action Indicated) - individual, non-critical comments that do not require the intervention of regulatory bodies, this comment was made as to 33 CTs. Only one inspection ended with an evaluation of the OAI (Official Action Indicated) - serious violations requiring regulatory intervention. ^[348] Thus, the separation of violations admitted in the course of CT in terms of their seriousness, found its consolidation in the activities of international regulatory bodies (in contrast to the current Russian legislation). At the same time, the criterion that allows to distinguish these violations is the consequences of the violations committed. Conventionally, they can be divided into procedural violations, that is, violations related to the procedure for carrying out the CT itself, regulated by law, including documentary fixation, notification of the Russian Ministry of Health and other formal requirements. Since these violations do not entail violations of the rights of the patient and do not affect the results of the trial, they are disposable and do not require the use of punitive mechanisms of regulatory bodies. Serious violations, in which regulatory intervention is mandatory, are the violations related to the safety of patients in the CT and the reliability of the data obtained.

Accordingly, it seems reasonable to legislatively fix the classification of all violations, taking into account the arguments expressed. In the first category there are violations of the CT organization procedures, i.e. formal violations. In the second category there must be violations of the rules of good clinical practice, which can potentially affect the rights and interests of the patient in CT and the reliability of CT data, i.e. significant violations. It can be assumed that by introducing on 01.07.2015 an amendement in the Law on the circulation of medicines providing that the violation of the rules of proper clinical practice, the falsification of the results of a clinical study of a medicinal product for medical use do entail responsibility in accordance with the legislation of the Russian Federation, the legislator has applied that very approach. Defining the objective side of violations in CT, for which it is possible to bring to legal liability, these delicts were considered as the most serious ones posing a significant threat to public relations. However, in spite of the imperative requirement of the article of the law on bringing to responsibility in accordance with the legislation of the Russian Federation, such norms on liability did not appear in the existing legal instruments.

It seems reasonable to share the opinion of the well-known scientists in the field of the theory of law N.I. Matusow and A.V. Malko, who believe that "legal liability is the state's legal implementation activity, in particular in such form as the application of legal norms to offenders, and because this responsibility and its results are directly and inevitably dependent on the effectiveness of this activity." ^[349] In this regard, based on the principles of consistency and the inevitability of legal liability for the admitted significant violations of the requirements of the law in the conduct of CT, it is necessary to formulate the compositions of both an administrative offense and a criminal offense, depending on the degree of public danger of the committed act. So, the composition of a criminal offense can be formulated for those cases when there is a deliberate falsification of the results of CT, as well as when the patient's health is seriously harmed or a fatal outcome has occurred. In this context, as an example, we can consider the norm introduced on July 5, 2012 in the Criminal Code of Ukraine (Article 3212), which reads:

"Violation of the established procedure of preclinical study, clinical trials and state registration of medicinal products":

" 1. Intentional violation of the established procedure of preclinical study, clinical trials, falsification of their results, as well as violation of the established procedure for state registration of medicinal products - shall be punished with imprisonment of three to five years with deprivation of the right to hold certain positions or engage in certain activities for a period of one to three years.

2. The same actions committed repeatedly or by prior agreement by a group of persons are punishable by imprisonment for a term of five to eight years, with deprivation of the right to hold certain positions or engage in certain activities for a period of two to three years.

3. The actions envisaged by parts one or two of this article, if they entailed the death of the victim or other grave consequences, are punishable by imprisonment for a term of eight to ten years with the deprivation of the right

to hold certain posts or engage in certain activities for a period of two to three years ".^[350]

The resulted legal experience of Ukraine given that it has established criminal liability for crimes in sphere of CT can serve as a positive example and for the legislation of the Russian Federation. However, it seems justified to ensure even more details of the unlawfulness and degree of public danger for this category of offenses and, in this connection, the establishment of a more differentiated responsibility, not only by criminal law means, but also by the rules of administrative law.

In cases where the intent to deceive when providing false information in the CT is absent, as well as significant violations did not cause serious harm to the life and health of the patient in CT, it is necessary to limit with administrative liability, which should play a decisive role for the following reasons.

First, administrative liability has a wide range of subjects, which are legal entities, officials and individuals. Practice shows that for violations committed in the conduct of CT, all subjects (such as the Medical Entity, the head of the medical entity, the physician-scientist in case he is recognized as an official) can be brought to administrative liability, because the activities of each of them can form a separate part of the offense.

Secondly, it is possible to envisage various types of punishments, which operate under administrative law, such as: administrative fine; deprivation of a special right granted to an individual; disqualification; administrative suspension of activities. Particularly effective in this case, is the withdrawal or suspension of the accreditation for the CT for a certain period - for the entity, as well as exclusion from the register of the main researchers and disqualification, that is, depriving the principal physician-scientist of the right to carry out medical activities in the field of CT for a certain period.

Thirdly, in the Russian jurisdiction there is already a law enforcement practice of bringing to administrative liability for similar offenses in the provision of medical care and in the sphere of medicinal products circulation. Thus, the Code of Administrative Offenses of the Russian Federation provides for such offenses as: 6.28. Violation of the established rules in the sphere of medical devices circulation, 6.3. Violation of legislation in the field of sanitary and epidemiological welfare of the population, 6.31. Violation of legislation on blood donation and its components, 6.33. Treatment of counterfeit, low-quality and unregistered medicines, medical products and turnover of adulterated biologically active additives. At the same time, as it was stated earlier, Roszdravnadzor, in accordance with paragraph 5.8 (2) of the Regulations, has the power to bring to administrative liability in accordance with the legislation on administrative offences.

Among other things, the relevance of the introduction in the Russian legislation of the norms on liability for significant violations committed during the CT is dictated by the need to comply with the provisions of international legal instruments that leave the authority to fix protective mechanisms aimed at minimizing risks for subjects and determining sanctions for violations CT, and national jurisdictions.

In addition to introducing the institution of legal liability for violations committed during the CT for the purposes of social protection of patients, as well as for an unlimited number of persons who are potential drug users, the legal procedures governing the suspension for a certain period should be developed, as well as the cessation of CT under applicable regulatory legal instruments. In addition, Roszdravnadzor should be given the authority to review the results of CT (including the power to cancel the results) in cases when inspections of already completed CTs reveal possible unreliable information as to the safety and efficacy of tested medication.

2.3.