which document created in 1964 forms the basis of ethical considerations in clinical research

What are the ethical considerations in clinical research?

Informed consent, confidentiality, privacy, and safety of subjects are key considerations in ethical research. Finally, it is the moral duty of the investigator, the members of the ethics committee, sponsors, clinicians, or any other person directly or indirectly involved in clinical study, to follow the principles of clinical research ethics.

What is the purpose of the ethics in Clinical Research Act?

It is considered to be the foundation document for ethics in clinical research and the first document to set out ethical principles/regulations on human experimentation based on informed consent.

What are the standards for conduct of clinical research?

must be stressed that the standards as drafted are only a guide to physicians all over the world. own countries. subjected to the research. 1. Clinical research must conform to the moral and scientific principles that justify medical established facts. 2. Clinical research should be conducted only by scientifically qualified persons and under

Which research papers were reviewed for ethical approval and patient consent?

A consecutive series of research papers published in the Annals of Internal Medicine, BMJ, JAMA, Lancet and The New England Journal of Medicine between February and May 2003 were reviewed for the reporting of ethical approval and patient consent.

What is the Declaration of Helsinki 1964?

Declaration of Helsinki, formal statement of ethical principles published by the World Medical Association (WMA) to guide the protection of human participants in medical research. The Declaration of Helsinki was adopted in 1964 by the 18th WMA General Assembly, at Helsinki.

What is the Nuremberg Code and the Declaration of Helsinki?

The Nuremberg Code focuses on the human rights of research subjects, the Declaration of Helsinki focuses on the obligations of physician-investigators to research subjects, and the federal regulations emphasize the obligations of research institutions that receive federal funds.

What did the Helsinki Declaration do?

The Declaration of Helsinki provided guidance for physicians who were conducting clinical research and focused on researchers' roles and responsibilities when it comes to protecting human subjects. The Declaration of Helsinki is seen as the first major attempt of the medical community to police itself.

What was the first document to declare ethical standards on human research?

The history of the declaration has been well documented. The Nuremberg Code (1947) was one of the first statements of the ethical principles involved in human experimentation.

What is the National Research Act of 1974?

In 1974, the National Research Act was signed into law, creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research . The group identified basic principles of research conduct and suggested ways to ensure those principles were followed.

What led to National Research Act 1974?

In 1997, under mounting pressure, President Clinton apologized to the study participants and their families. National Research Act (1974): due to the publicity from the Tuskegee Syphilis Study, the National Research Act of 1974 was passed.

What is the Declaration of Helsinki 2008?

Abstract. The Declaration of Helsinki (DoH) was adopted by the World Medical Association (WMA) in 1964, as a statement of ethical principles, to provide guidance to physicians and other participants in medical research involving human subjects.

Why was the Belmont Report created?

The Belmont Report was written in response to the infamous Tuskegee Syphilis Study, in which African Americans with syphilis were lied to and denied treatment for more than 40 years. Many people died as a result, infected others with the disease, and passed congenital syphilis onto their children.

What is true about the Belmont Report of 1979?

In its Belmont Report, the National Commission on Protection of Human Subjects in Biomedical and Behavioral Research (1979) reviewed and reaffirmed the ethical principles that should guide everyone engaged in research involving human subjects.

When did the code of ethics first introduced?

The 1948 Nuremberg Code is the first ethical code to establish the basic standards for when human beings may be enrolled in scientific studies, including informed consent, a balancing between plausible benefits to humanity and harm to individuals, and the individual's right to disenroll at any time.

When was Helsinki Declaration declared?

1964The World Medical Association's Declaration of Helsinki was first adopted in 1964. In its 40-year lifetime the Declaration has been revised five times and has risen to a position of prominence as a guiding statement of ethical principles for doctors involved in medical research.

What is the history of the development of research ethics?

Out of the horrors of World War II came the Nuremberg Code, the prototype for human research protection. We can trace today's research ethics principles directly to the inhumane experimentation on prisoners in the Nazi death camps during World War II.

Was the Helsinki Declaration written during the Nuremberg trials?

The Declaration of Helsinki was created following the Nuremberg Trials, in which many individuals who were involved in Nazi experimentation on humans were prosecuted with crimes against humanity.

Which basic principles of research ethics can be summarized from the Nuremberg Declaration Declaration of Helsinki and Belmont Report?

Which basic principles of research ethics can be summarized from the Nuremberg Declaration, Declaration of Helsinki, and Belmont Report? (1)The principles of fair treatment, explicit communication of the obligations of the researchers, informed consent of the participants, and protection of the participants' privacy.

Which of the following is included in the Nuremberg Code?

The ten points became known as the Code, which includes such principles as informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants.

What was the importance of the Nuremberg Code and the Belmont Report?

History of the Belmont Report The Nuremberg Code set the example for subsequent codes that established rules to help protect human subjects involved in research. But these rules were found to be inadequate to cover complex situations, at times in conflict, and frequently difficult to interpret or apply.

What was the 5th revision of the WMA?

The fifth revision—which was adopted by the WMA General Assembly in Edinburgh, Scotland, in 2000—was substantial, and many of the changes made were viewed as controversial in the medical community. The fifth revision reorganized the structure of the document and expanded it by creating a nine-paragraph introductory section (which broadened the scope of the declaration to include scientists as well as physicians) and sections describing various principles of medical research. It augmented the oversight powers of ethical review committees and adjusted the language related to placebos in medical studies. Debate ensued about revisions to the declaration, with some medical practitioners arguing for stronger language and commentary addressing clinical trials and others proposing to limit the document to basic guiding principles. Although a consensus was not reached, the WMA approved the revision.

Why was the fifth revision of the placebo declaration rejected?

Food and Drug Administration rejected the fifth revision in 2007 because of its restrictions on the use of placebo conditions and eliminated all references to the declaration, replacing it with the Good Clinical Practice guidelines, an alternate internationally sanctioned ethics guide. In addition, the National Institutes of Health training in research with human participants no longer refers to the declaration, and the European Commission refers only to the fourth revision.

What is the Declaration of Helsinki?

Declaration of Helsinki, formal statement of ethical principles published by the World Medical Association (WMA) to guide the protection of human participants in medical research. The Declaration of Helsinki was adopted in 1964 by the 18th WMA General Assembly, at Helsinki. Although not without its controversies, ...

What is the WMA's position on placebos?

In paragraph 29 the WMA noted that use of placebos was considered acceptable in situations where the reasons for doing so were either “scientifically compelling” or where the medical condition under study was not serious and the patient would not be placed at increased risk of serious or irreversible harm. In paragraph 30 the WMA called for detailing “post-trial access arrangements” for ethical review committees, which would presumably comment on their feasibility.

What were the ethical principles of research before World War II?

Before World War II, no formal international statement of ethical principles to guide research with human participants existed; researchers were left to rely on organizational, regional, or national policies or their own personal ethical guidelines. After atrocities were found to have been committed by medical researchers in Germany who used involuntary unprotected participants drawn from Nazi concentration camps, the 1947 Nuremberg Code was established. That was followed in 1948 by the WMA’s Declaration of Geneva, a document outlining every physician’s ethical duties, which included pledges to focus on the health of the patient and not to use medical knowledge to violate human rights. Both documents influenced the development of the Declaration of Helsinki. The initial declaration, which was less than 2,000 words long, focused on clinical research trials. Notably, it relaxed conditions for consent for participation, changing the Nuremberg requirement that consent is “absolutely essential” to instead urge consent “if at all possible” and to allow for proxy consent, such as from a legal guardian, in some instances.

What is the meaning of paragraph 30 of the study?

Paragraph 30, which called for every patient in the study be given access to the best health care methods identified by the study , was also considered controversial. The language of the passage implied that standards of medical care in developed countries should apply to any research with human beings, including research conducted in developing countries. In developing countries, per capita health care expenditures are much lower, and some medical practitioners argued that the rule placed too great a burden on researchers and their resources after conclusion of the study. The language appeared to mandate the provision of the same level of care to the patients in the study afforded to those in developing countries, which may require massive investments of staffing and capital. Some practitioners maintained that achieving equivalent levels of care would not be practical and would keep sponsoring organizations from funding placebo-related research in developing countries, whereas others argued that it would be unfair to keep the benefits of a medical treatment from the very patients whose participation helped develop them.

What was the purpose of the extermination camp?

Extermination camp, Nazi German concentration camp that specialized in the mass annihilation ( Vernichtung) of unwanted persons in the Third Reich and conquered territories . The camps’ victims were mostly Jews but also included Roma (Gypsies), Slavs, homosexuals, alleged mental defectives, and others.

What is the definition of clinical trial?

13. An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial. 14.

What is clinical practice?

Good clinical practice provides a framework of principles that aim to ensure the safety of research participants and that the clinical properties of the investigational product are adequately documented.

What is systematic and independent examination of trial-related activities and documents?

A systematic and independent examination of trial-related activites and documents to determine whether the evaluated trial-related activities were conducted and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor's SOPs, GCP, and the applicable regulatory requirements. A.

What does "study involves research" mean?

1. “Statement that the study involves research”. “Description of the procedures to be followed”. “The trial procedures to be followed, including all invasive procedures”. “Description of the procedures to be followed, including all invasive procedures”. “The expected duration of the subject’s participation”.

What are the essential elements of a study?

Essential Elements. 1. “Statement regarding research, purpose, procedures, duration , etc.”. 1. “A statement that the study involves research, an explanation of the purposes of the research”. 1. “That the trial involves research and the purpose of the trial”. 1. “Statement that the study involves research”.

What is informed consent?

The informed consent process is considered to be vital to ethical conduct of clinical research . The basic principle of an informed consent is that individuals, after receiving and understanding the necessary information (without any undue inducement or intimidation) are entitled to choose freely whether to participate in research or not, thus following the principles of autonomy. Prior to participation, the subject or the subject’s legal representative should receive a copy of the signed and dated informed consent form [18]. There are several key elements of an effective informed consent process summarized below which have been defined in various guidelines including the CIOMS, ICH-GCP and Schedule Y guidelines. As per the Code of Federal Regulations, CFR (title 21, volume 1, part 50B) [31], there are eight basic elements of an informed consent document ( Table 14.1 ). Briefly, it should include: (1) A statement that the study involves research, explaining its purpose, expected duration, and description of procedures to be followed; (2) Defining any foreseeable risks and discomfort to the subjects; (3) Any benefit to the subject or to society; (4) Any alternative procedure or treatment that might be advantageous to the subject; (5) A statement regarding maintaining confidentiality of records and that they may be subjected to inspection; (6) Details regarding compensation and treatment provided in case of injury to the subjects; and (7) A statement regarding voluntary participation and that the subject may discontinue at any time without penalty or loss of benefit. Some additional elements include a statement regarding unforeseeable risks, circumstances under which subject’s participation may be terminated, consequences of a subject’s decision to withdraw from the research, providing information to the subject regarding any new findings developed during the course of study, approximate number of subjects involved in the study, etc. [29], [30]. Though the basic elements of the informed consent document as specified in 21CFR50 are similar in other guidelines, a comparison of these with ICH-GCP and Indian-GCP guidelines is depicted in Table 14.1 with only minor differences.

What are the CIOMS guidelines?

Many other guidelines were subsequently developed including the International Ethical Guidelines for Biomedical Research involving Human Subjects (1982; revised in 1993, 2002), prepared by the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization (WHO) to help developing countries apply the principles of the Declaration of Helsinki and the Nuremberg Code. The CIOMS guidelines (2002) ( http://www.cioms.ch/publications/layout_guide2002.pdf) [16] include 21 guidelines (15 in the original report) and are under the process of revision since, despite several changes in the field of research ethics, the guidelines were not revised after 2002. In 2011, a working group was constituted to revise the guidelines, and the major revisions recommended were the guideline on risks and benefits (Guideline 8), choice of control (Guideline 11), and women (Guideline 16). Guidelines 4 and 6, which are both on informed consent, were proposed to be merged. Further, the Green Book (the CIOMS Guidelines for Biomedical Research) with the Blue Book (the CIOMS Guidelines for Epidemiological Research) were also proposed to be merged together [16].

What are the four ethical principles?

The four basic ethical principles were described in biomedical ethics in 1979 [14] and the Belmont Report was published by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, US [15]: (1) Beneficence: meaning “maximize possible benefits and minimize possible harms”; (2) Non-maleficence: meaning “avoidance of harm” ( included under Beneficence in Belmont Report ); (3) Autonomy: meaning free and informed participation, respect for persons , persons with diminished autonomy (vulnerable) are entitled to protection; and (4) Justice: meaning benefits a burden of disease to be fairly distributed among entire population (for selection of subjects, etc.). The above principles of the conduct of research require:#N#1.#N#Informed consent: This has a further three important components:#N#a.#N#Information: concerning procedure, purposes, risks, anticipated benefits, alternative procedures (where therapy is involved), and a statement offering the subject the opportunity to ask questions and to withdraw at any time from the research, etc.#N#b.#N#Comprehension: the manner in which information is conveyed is equally important and is the responsibility of the Investigators.#N#c.#N#Voluntariness: An agreement to participate in research means informed consent given free of coercion and undue influence.#N#2.#N#Assessment of risks and benefits: Brutal or inhumane treatment of human subjects is never justified. Risks should be reduced by careful attention to alternative procedures. Review committees should evaluate thoroughly the justification given in case of significant risks of serious impairment. Relevant risks and benefits must be thoroughly provided in documents and procedures used in the informed consent process.#N#3.#N#Selection of subjects: Certain groups, such as racial minorities, the economically disadvantaged, the very sick, and the institutionalized may continually be sought as research subjects, due to their easy availability. The vulnerable population, owing to their dependent status and their compromised capacity for free consent, should be protected against the danger of being involved in research.

What is the Declaration of Helsinki?

The Declaration of Helsinki (DoH), developed by the World Medical Association (WMA), is a statement of ethical principles for medical research involving human subjects. It was adopted by the 18th WMA General Assembly held in Helsinki, Finland in 1964, and subsequently amended in the WMA General Assembly meetings held in Japan (1975), Italy (1983), Hong Kong (1989), South Africa (1996), Scotland (2000), Seoul (2008), and more recently Brazil (2013). A note on clarification (on two paragraphs—P29 and P30) was added in the WMA meetings held in Washington (2002) and Tokyo (2004). According to DoH, it is the duty of the physician to promote and safeguard the health of patients, including those who are involved in medical research, and that the wellbeing of the individual research subject must take precedence over all other interests. The declaration also included protection for the vulnerable population, the need for proper designing of research protocol, its approval and monitoring by research ethics committees, principles of maintaining confidentiality and privacy of research subjects, and described a written informed consent process [9]. However, the FDA in 2008 abandoned the DoH fourth revision (1996) by restricting the use of placebos where proven interventions had become established. This had major implications for research in resource-poor nations, where placebos were being used in such situations. The International Conference on Harmonization Good Clinical Practice (GCP) was designated as the new regulatory standard by the FDA [10]. The recent 7th revision of DoH in 2013 includes 37 principles categorized under various subsections for clarity [11], [12]. Some of the notable changes in the new version of the DoH are [13]: (1) need to include under-represented groups in research (P13); (2) ensuring compensation to research participants (P15); (3) increasing protection for the vulnerable population (P20); (4) posttrial access to care (P34); (5) post-study requirements for reporting results to participants (P36); and (6) use of unproven interventions (P37). The new version, thus, aimed to prevent exploitation of research subjects and calls for greater protection of vulnerable groups, and for the first time declares compensation and treatment for those injured during the study [9]. The DoH is again not a legal document. Nevertheless, many organizations follow the same while framing ethical guidelines and the document is revised and updated.

What historical event influenced human research ethics?

The historical event that majorly influenced human research ethics due to violation of fundamental human rights was the experiment on war prisoners at the end of World War II by Nazi physicians at Nuremberg, Germany. The trials were conducted by the US on physicians convicted on the basis of various torturous experiments, the most horrifying experiment being placing the subjects in a pressure chamber to simulate conditions that German pilots might encounter under high-altitude, low-pressure conditions with no oxygen or pressure suits [4]. The judgment of these trials formed the Nuremberg code in 1947 [5]. It is considered to be the foundation document for ethics in clinical research and the first document to set out ethical principles/regulations on human experimentation based on informed consent. Later, however, it was shown that informed consent in human experimentation guidelines existed well before the Nuremberg code [6] and that six of the ten principles of Nuremberg code were based on the Guidelines for Human Experimentation of 1931 [7]. The ten ethical principles laid down in Nuremberg code are shown in Box 14.1. Though most of the principles are the cornerstone of human research ethics, principle number 5, involving self-experimentation, was debated. It wasn’t considered justifiable to put the lives of others at risk just because the investigator is willing to risk his own life [8]. The Nuremberg code is not legally binding, and unlike the Declaration of Helsinki, it is not regularly reviewed and updated.

What is the purpose of FDA regulations?

FDA regulations confer protections on human subjects in research when a drug, device, biologic, food additive, color additive, electronic product, or other test article subject to FDA regulation is involved.

Why did the FDA pass the Kefauver Amendments?

Senate hearings followed and in 1962 the so-called “Kefauver Amendments” to the Food, Drug, and Cosmetic Act were passed into law to ensure drug efficacy and greater drug safety. For the first time, drug manufacturers were required to prove to the FDA the effectiveness of their products before marketing them.

What was the purpose of the National Research Act of 1974?

This commission was tasked with identifying the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects. It was also tasked with developing guidelines that should be followed to assure that such research is conducted in accordance with these ethical principles.#N#The commission drafted the Belmont Report, a foundational document in for the ethics of human subjects research in the United States.

How did the study of syphilis end?

Many subjects died of syphilis during the study. The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its existence was publicized and it became a political embarrassment. In 1997, under mounting pressure, President Clinton apologized to the study subjects and their families.

How long did the syphilis study last?

Public Health Service. Six hundred low-income African-American males, 400 of whom were infected with syphilis, were monitored for 40 years. Free medical examinations were given; however, subjects were not told about their disease. Even though a proven cure (penicillin) became available in the 1950s, the study continued until 1972 with participants being denied treatment. In some cases, when subjects were diagnosed as having syphilis by other physicians, researchers intervened to prevent treatment. Many subjects died of syphilis during the study. The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its existence was publicized and it became a political embarrassment. In 1997, under mounting pressure, President Clinton apologized to the study subjects and their families.

What is the Declaration of Helsinki?

In 1964, the World Medical Association established the “Declaration of Helsinki,” which provides recommendations guiding medical doctors in biomedical research involving human subjects. The declaration governs international research ethics and defines rules for “research combined with clinical care” ...

What is the common rule of federal policy?

The main elements of the Common Rule include the following: requirements for assuring compliance by research institutions; requirements for researchers obtaining and documenting informed consent;

What is the meaning of 3A?

3a. Clinical research on a human being cannot be undertaken without his free consent after he. has been informed; if he is legally incompetent, the consent of the legal guardian should be. procured. 3b. The subject of clinical research should be in such a mental, physical and legal state as to be.

What is the mission of a doctor?

It is the mission of the doctor to safeguard the health of the people. His knowledge and. conscience are dedicated to the fulfilment of this mission. The Declaration of Geneva of The World Medical Association binds the doctor with the words: “The health of my patient will be my first consideration” and the International Code of Medical.

What is special caution?

in comparison to foreseeable benefits to the subject or to others. 5. Special caution should be exercised by the doctor in performing clinical research in which. the personality of the subject is liable to be altered by drugs or experimental procedure. 2.

What is clinical research?

1. Clinical research must conform to the moral and scientific principles that justify medical. research and should be based on laboratory and animal experiments or other scientifically. established facts. 2. Clinical research should be conducted only by scientifically qualified persons and under.

Can a doctor combine clinical research with professional care?

The doctor can combine clinical research with professional care, the objective being the. acquisition of new medical knowledge, only to the extent that clinical research is justified. by its therapeutic value for the patient. III.

Can clinical research be carried out?

Clinical research cannot legitimately be carried out unless the importance of the objective. is in proportion to the inherent risk to the subject. 4. Every clinical research project should be preceded by careful assessment of inherent risks. in comparison to foreseeable benefits to the subject or to others. 5.

Nuremberg Code

Thalidomide

Tuskegee Syphilis Study

Declaration of Helsinki

• In 1964, the World Medical Association established the “Declaration of Helsinki,” which provides recommendations guiding medical doctors in biomedical research involving human subjects. The declaration governs international research ethics and defines rules for “research combined with clinical care” and “non-therapeutic research.” The Declaration o...

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National Research Act