In medical biology, it is impossible to conduct basic research and apply their results in the treatment without the experiments on humans, known as “clinical studies” or “experiments on human beings.”
Such experiments can not replace research on tissues in vitro or in laboratory animals (including primates), because the animal differs from the human in anatomical, physiological, and pharmacokinetic characteristics, and also by the reaction of the organs and systems in medicine. For example, it is known that thalidomide is harmless to rodents, but has a teratogenic effect in humans; morphine calms and excites the human cats, insulin is very toxic to guinea pigs and hamsters, but absolutely indispensable in treating people suffering from diabetes. In addition, some diseases are peculiar only to man, and they can not be simulated in laboratory animals. Even in studies in healthy volunteers is difficult to reliably reproduce the effects that will cause the drug in patients.
Clinical studies in humans are fundamentally kind of scientific activities, without which it is impossible to obtain, and the selection of new, more effective and safer drugs, as well as “purification” of medicine from the old ineffective drugs.
Recently, the role of clinical trials has also increased due to the introduction of practical public health of evidence-based medicine, the main one being the adoption of specific clinical decisions for patient care is not so much based on personal experience of the doctor as the basis of proven scientific evidence strongly controlled experiments.
However, given that the conduct of clinical trials is essential to the final stage of the case study, their conduct is unsafe and does not pass in vain for those who serve as material for such experiments. Any experiment carries a greater or lesser element of risk to the patient. The very nature of the relationship between the researcher and the subject is that the goal of significantly different: if the first at the forefront – to provide new knowledge, then the second one, naturally – improved health status. This, of course, is not about cruelty, malice, or indifference to who conducts an experiment, and the objectively existing conflict of interest that raises a number of legal, ethical and deontological questions: whether acceptable clinical experiments on humans, and if so, what should be restrictions and conditions for their implementation? How to reduce the potential risk to the patient’s condition to ensure confidentiality? As genetic testing drugs on healthy volunteers? How to avoid possible misuse of research? How to organize the study, taking into account peculiarities of law and social conditions in different countries, as well as observe and protect the rights of people who took part in them?
These and many other issues require special attention and are the object of learning a new field of knowledge known as bioethics. Under this very general term, the introduction of the Van Rensellerom Potter in 1974, we understand the “systematic analysis of human action in biology and medicine in the light of moral values and principles.” Bioethics (sometimes referred to as biomedical ethics), which is now growing rapidly throughout the world, engaged not only in research but also develop ways and means to resolve problem situations that arise in practical and health and in the field of new medical technologies.
In recent decades, global practice promotion and protection of human rights, an increasingly prominent place is that an extremely large portion of those rights, which is implemented (or not implemented) in the field of biomedicine. This area includes, firstly, the problems arising when and where and when a person acts as the patient interacts with the doctor and with health services in general. Second, this includes everything that is related to the protection of human rights and dignity, when it is exposed to new medical technologies. Here it is often the subject – a party of biomedical experiments. However, in actual practice it is difficult to distinguish between ordinary medical care and high-tech medicine, because modern medical practice is increasingly intertwined with scientific experiments and testing of new drugs and medical technologies for humans.
Basic ethical and legal principles governing the conduct of clinical trials have been formulated in the Declaration of Helsinki of the World Medical Association adopted the 18th General Assembly of the World Medical Association in June 1964 (Amended: 29 th General Assembly of the World Medical Association in Tokyo in October 1973, 35th WMA General Assembly in Venice, Italy, in October 1983, 41 th General Assembly of the World Medical Association in Hong Kong in September 1989, 48th WMA General Assembly, Somerset – West, South Africa in October 1996 and 52 th General Assembly of the World Medical Association in Edinburgh, Scotland, in October 2000)
It says that biomedical research involving human subjects must conform to generally accepted scientific principles, be based on adequately performed laboratory and animal experiments, as well as adequate knowledge of the scientific literature. They should be performed by qualified personnel under the supervision of an experienced physician. In all cases, the responsibility for the patient is a doctor, but not the patient, although the subject has given informed consent.
In any research involving human subjects, each potential participant must be adequately informed about the aims, methods, anticipated benefits of research and associated with participation in the study of the risk and inconvenience. Participants should be aware that they are entitled to abstain from participation in the study and that they may at any time after the start to withdraw your consent and refuse to continue the investigation. Then the doctor must obtain from the subject’s freely given informed consent in writing.
Biomedical research involving human subjects can not be conducted legally, if the risk to research subjects are disproportionately large compared with the importance of the objectives of the experiment. In any biomedical research the lives and health of the subjects are always above the interests of science and society.
Outlined in the Declaration of Helsinki principles are merely recommendatory provisions, but its significance for modern law can not be overestimated. Any country, manufacturer, medical scientists must conduct research in accordance with these rules if they want their results were accepted by the international community. That the Declaration of Helsinki of the World Medical Association formed the basis of all subsequent laws that define human rights and ethical obligations that take on the doctors in clinical research.
November 19, 1996 the Parliamentary Assembly of the Council of Europe was finally adopted the Convention on the protection of human rights and human dignity in the application of biology and medicine.
At first it was a convention on bioethics, but in the final text was agreed to renounce the use of this term (although in everyday, informal discourse, it is often continue to call it so). One of the main reasons for this change – that the Convention is a legal document, so use it the word “ethics” can be misleading. In other words, the rules laid down in the Convention are not only a moral appeal – each State acceding to it, undertakes to fulfill “its main provisions in national legislation” (Article 1).
Recorded at the Convention provisions to protect the dignity and identity of human beings and guarantee everyone, without discrimination, respect for their integrity and other rights and fundamental freedoms with regard to the application of biology and medicine, including transplantation, genetics, psychiatry, etc.
According to the fifth chapter of this document, human studies are conducted only under the following conditions:
There is no alternative test methods that are comparable in their effectiveness;
risks which may be incurred by that person does not exceed the potential benefits of the research;
research project has been approved by the competent body after independent examination of the scientific validity of the study, including the importance of its objectives, and multidisciplinary review of its acceptability from an ethical point of view;
person acting as the subject, informed of their rights and the safeguards prescribed by law;
provided written informed consent to the experiment, which can be freely withdrawn at any time.
Studies on humans have no legal authority to consent to their participation in the experiment can be conducted only if there is a specific written authorization from the trustees and the person concerned does not object, provided that the expected results of the study suggest a direct benefit to his health subject. It is not recommended to carry out experiments on patients found incompetent, when similar studies can be conducted with comparable effectiveness on individuals capable of giving consent to it.
Conducting clinical trials that are not able to give direct benefit to the health of the subject is allowed only in exceptional cases:
if the study extends scientific knowledge about the health of the subject, disease or directed to obtain such outcomes, which may have beneficial effects on the health of the subject or other persons belonging to the same age category suffering the same disease (or disorder) or having the same condition;
If participation in this study involves minimal risk or inconvenience for most of the test.
Of course, the first scientists embraced regulations that establish strict limits for the conduct of clinical trials, not without resistance. So, Henri Poincare found ridiculous the very idea that the parliaments of different countries can make informed decisions on scientific research. He wrote: “It should be guided by their conscience, any legal intervention would be inappropriate and somewhat ridiculous.”
In the debate on mandatory informed consent of patients as an argument research scientists say that for methodological reasons, to guarantee the objectivity of the results of experiments are needed, “doubly ignorant.” In addition, the results of the experiments has an impact bias, especially in the case of volunteers (the so-called – the placebo effect).
Concerns have been raised and about the possibility of excessive bureaucratization of biomedical research. It is, of course, there is, as with any other activity. However, it must be balanced with the potential dangers for the individual to the medical community, and society at large posed by the lack of control in the experiments.
Currently, 40 countries of the Council of Europe for more than 20 have joined the Convention. Russia has not yet signed it, but it is not in any fundamental objections, and that there is no state agency, develops and implements policies in the field of bioethics.
The Convention on Human Rights and Biomedicine requires the State not only to proclaim its principles, but also to ensure their actual implementation, which is especially important for Russia, because in our country, the gap between the written rules of the law and actual practice can be arbitrarily large. Appropriate authorities of the Council of Europe have the right to monitor compliance with the Convention in each of the signatory countries.
The central part of this control are, firstly, the independent ethics committees that are created in those research institutions that conduct experiments on humans and animals. In Russia in 1998 for the rights of patients in clinical trials, watching the Ethics Committee of Medical Sciences, Ethical Committee of the MMA. IM Sechenov, and the Ethics Committee of the PMA clinical trial – an independent body, which consists of doctors, lawyers, journalists, experts in medical advertising. It assesses not scientific (it is the prerogative of the Ministry of Health), and the ethics of proposed research and ensure the rights of patients. No one clinical trial may not begin before the Ethics Committee will give “good” developers and researchers, making sure that does not infringe any rights of patients, and they are not exposed to undue risk.
Second, the policy of scientific journals is that they do not accept for publication articles, for which there is complete clarity that the experiments, expressed in them were carried out in strict accordance with existing ethical standards. Thus, a study conducted in violation of the ethical and legal norms, simply deprived of the opportunity to claim to be – science.
Organizers (sponsors) of the clinical experiment can be pharmaceutical companies or researchers themselves. Sponsor is responsible for organizing and conducting research in general. To do this he must develop a research protocol, to provide researchers have studied the drug, manufactured and packaged in accordance with the standards of GCP, and complete information about it. Information should include all pre-clinical and earlier clinical trials, including details of all adverse drug reactions. Insurance patients and researchers is also the responsibility of the sponsor.
The researchers, primarily responsible for the ethical and practical application of work in the clinic, as well as for the health and well-being of patients during the study. Clinical trials can be carried out only physicians with appropriate qualifications and official permission to engage in medical activities. The component elements of research training is their training and special training in clinical trials and the rules of GCP.
Researchers must always be prepared to audit the quality of their work. Inspections are divided into several types: monitoring, audit and inspection. Monitoring regularly checks as a respected ethical conduct of research and study protocol, as well as the quality of filling the documentation. The audit is usually performed only one time in the most important studies. The audit is to verify compliance with the rules of GCP, protocol and local laws. Duration of audit depending on the complexity of research and may take several days. The Inspectorate has the same purpose, it carried the official control and permitting authority.
With regard to domestic legislation, the conduct of clinical trials in Russia is governed by the Constitution of the Russian Federation, Federal Law “Principles of Legislation on health protection of citizens” from 22.07.1993 and the Federal Law “On Medicines” on 22.06.1998, having a separate chapter IX «Development preclinical and clinical studies of drugs. ”
It should be borne in mind that, under current law in our country, international treaties and agreements in which Russia participates, have priority over the Russian domestic law. This means, firstly, that in the absence of our law of relevant international standards in Russia have a direct effect. Second, if a rule of domestic law is in conflict with the internationally accepted norm, it must be guided by the latter.
The principle that asserts the priority benefit of the individual over those of science and society, written in the article 21 of the Russian Constitution: “… no person shall be subjected without free consent to medical, scientific and other experiments.”
Article 43 of “Principles of Legislation on health protection of citizens’ contains a provision that the conduct of biomedical research is allowed in the institutions of state or municipal health care system and should be based on previously conducted a laboratory experiment.
Any biomedical research involving human subjects as an object can be done only with prior written consent of the citizen. A citizen can not be compelled to participate in biomedical research.
When obtaining informed consent for biomedical research citizen should be given information about the aims, methods, side effects, risks, duration and expected results of the study. A citizen has the right to refuse to participate in the study at any stage.
The Federal Law “On Medicines” regulates relations arising in connection with the development, production, manufacturing, preclinical and clinical studies of drugs, control their quality, efficiency, security, trade, drugs and other actions in the drug market. According to the law of clinical trials can be conducted only at clinics that are licensed. Licenses are issued only to those hospitals that can provide the clinical trials of medicines in accordance with the rules of GCP.
Thus, according to Article 39 of this document, the head of health services, conducting clinical trials of medicinal product, must approve the program of experiment and assign it to the head, which can only be a doctor with experience in the field of medical research at least two years. The program itself is designed experiment involving the ethics committee at a health facility, conducting clinical trials of the drug.
Head of the experiment must be familiar with the results of preclinical studies of the drug and is entitled to receive any additional information with respect to this drug.
Clinical studies can be interrupted at any time, if in the process of conducting health risk detected patients. The decision to terminate the experiment made by the head of the program.
Violation of the rules of clinical practice, as well as falsification of the results of clinical trials of drugs punishable under the laws of the Russian Federation.
With regard to patients’ rights, they are governed by Article 40 of the federal law, which states that people’s participation in clinical trials should be voluntary. The patient gives written consent to participate in a medical experiment, and it should be informed:
1) the medicinal product and the nature of clinical trials of this drug;
2) the expected effectiveness of the safety of the product, the risk to the patient;
3) the patient’s actions in the event of unforeseen effects of the influence of the drug on the state of his health;
4) the conditions of insurance of the patient.
The patient has the right to refuse participation in clinical trials at any stage of their conduct.
Not allowed clinical trials of drugs to minors, except in cases where the investigational agent designed exclusively for the treatment of childhood diseases, or when the purpose of clinical trials is to obtain data on the best dose of the drug for the treatment of minors. In the latter case, clinical studies in children should be preceded by similar tests on adults.
Prohibited from conducting clinical trials of medicines:
1) to minors without parents;
2) pregnant women, except when conducting clinical trials of medicinal products intended for pregnant women, and when not eliminate the risk of harm to a pregnant woman and fetus;
3) persons serving sentences in prisons, as well as on persons detained in detention centers, without their written informed consent.
Permitted clinical trials of drugs for the treatment of mental illness in persons with mental illness and found incompetent in the manner prescribed by the Law of the Russian Federation “On psychiatric care and guarantees of citizens’ rights in its provision.” Clinical trials of medicines in this case carried out with the written consent of the legitimate representatives of said persons.
Unfortunately, it should be noted that in Russia the importance of human rights in biomedicine understood enough, and in national legislation still did not reflect many of the norms contained in international agreements. Russia’s lack of instrument, comprehensively regulating clinical trials of medical products and thus compatible with those documents adopted in industrialized countries, on the one hand, prevents the participation of Russian scientific and medical institutions in such studies, on the other hand, it paves the way for potential abuse in this area.
Today, the ethics of biomedical experiments – is not nothing but wishful thinking. There are developed and tested methodology and practice of ethical and legal standards for such experiments, as well as structures and mechanisms are quite hard to monitor compliance with these standards. But modern medicine is becoming more sophisticated and powerful, the constantly expanding opportunities for effective impact on the deepest structures of the human body to the processes of human reproduction, to his mind, genetics, even in the process of dying. It is often said, and not without reason that many of the health effects faced by people today, are extremely aggressive. And, therefore, people need new legal mechanisms for protection.
Without clinical trials can not progress in the development of new drugs. But nothing, neither the interests of the scientist nor the interests of pharmaceutical companies, nor the interests of clinical pharmacology in general – should not be above the rights and interests of the person who is, legally speaking, the subject of study.