The Belmont Report

Since the Kefauver-Harris Amendmenf was adopted in 1962, pharmaceutical manufacturers have been held responsible by the FDA for providing new medications fhaf are bofh safe and effective. In addition to the Kefauver-Harris Amendment, the Belmont Report (written in 1979), established the ethical principles and guidelines for conducting research. The FDA requires that clinical trials be conducted in compliance with a protocol that has been... 

The Belmont Report s principle of beneficence refers to the need to ensure that all aspects of a study are designed to obtain the desired knowledge in a way that maximizes benefits and minimizes risks to the participants. The principle of beneficence also means that a risk-benefit analysis must be performed on every proposed study. In determining if fhis ratio is ethical, consideration must be given to the impact on both the participants and society. 

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Department of Health, Education, and Welfare, Washington, DC, April 18, 1979. 

The Belmont Report (24), in considering differences between the research and the clinical setting, noted that departure from commonly accepted drug practice for individual patients should not be considered research. Innovative strategies, however, should be developed in research protocols as quickly as possible to assure safety and efficacy of such a practice. 

Clinical safety studies are conducted in human volunteers to determine the safety of chemicals, drugs, formulations, devices, or other products, which may come in contact with the human body. Clinical safety testing should always be conducted prior to efficacy investigations in order to determine the benefit/risk ratio of efficacy trials. When designing a study, benefits and risks shall be balanced and shown to be in a favorable ratio (The Belmont Report). The rights, safety and well-being of the trial subjects are the most important considerations. (ICH Guidelines 2.3). 

The Belmont report describes the basic ethical principles that underlie research involving human subjects respect for persons, beneficence, and justice. The report discusses application of informed consent, assessment of ri.sks and benefits, and selection of subjects. Its regulations require that IRBs have not fewer than five members who have the capability to judge research proposals in terms of community attitudes. Therefore, IRBs must include people whose primary concerns lie in the areas of legal, professional, and community acceptance rather than in the overall scientific design. 

The Belmont Report (1979) contains the ethical principles on which the federal regulations for protection of human subjects are based. The three basic principles are respect for persons, beneficence, and justice. Respect is reflected by the consent process. As a result the term autonomy is used in the research and healthcare context. A patient is normally regarded as autonomous if he or she can make his or her own judgments and decisions. In the absence of such ability, for example, as in the case of children, prisoners, and those with mental disorders, the person must be protected. In the Belmont Report and Beneficence, beneficence is the process of minimizing harm (risk) and maximizing possible benefits (usually for the community as a whole). Justice is the term used for the criterion that subjects must be fairly drawn from a variety of ethnic, social, and other groups. 

Beauchamp and Childress (2001) advocate four principles -autonomy, beneficence, non-maleficence and justice - to form the basis of bioethics discussion. However, in paediatric research, the model of best interests of the child sets a paradigm of a combination of parental consent and assents by the child as advocated in the Belmont Report (1978) in the USA. 

Ethical considerations must be applied from the design to the completion of a clinical trial. Clear scientific hypotheses and objectives are critical. It is difficult to justify a clinical study if it is not clinically important or relevant. There are added ethical considerations for cancer patients, many of whom have been heavily pretreated with other chemotherapy agents and many of whom are terminally ill and may not derive any direct benefit from the agent being studied, particularly in phase 0 and I trials [23]. Clinical trials are conducted under guidelines issued in the Belmont Report of 1978 that protects human subjects and follows principles of respect for persons, beneficence, and justice. Scientific conduct is also guided by ethical principles in that competent and rigorous analysis is required to prevent compromise of the results [24]. 

In the United States it was as a direct result of the revelation of the Tuskegee Syphilis Study that the next U.S. medical ethics initiative emerged. The National Research Act of 1974 was passed (Public Law 93348), which required regulatory protection for human subjects and created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. In 1979 this commission produced the Belmont Report, named after the Smithsonian Institution s Conference Center, where the discussions were first held in 1976. The report established three ethical principles to allow problems to be solved in the area of ethics in clinical research (1) respect for persons, (2) beneficence, and (3) justice. In general terms, these categories were equivalent to informed consent, risk-benefit assessment, and an appropriate choice of subjects for the research. 

U.S. federal regulations were developed from the Belmont Report. They were adopted, in 1991 by 17 federal departments and agencies hence the term the Common Rule. This governs research conducted or supported by these departments and agencies. The regulations are called Title 45, Code of Federal Regulations 46 (45 CFR 46) Federal Policy for the Protection of Human Subjects. There are four parts ... 

As a consequence of these and other developments, in 1979 the USA issued its own policy document on the ethical conduct of research involving human subjects. Known as the Belmont Report, it is the basis for the complex regulatory framework that governs human subject research in the United States. The report maybe viewed online at http //ohsr.od.nih.gov/guidelines/belmont.html. 

Beauchamp, T. The legacy and the future. 30 years after the Belmont Report, Beauchamp sets the record straight. Prot Hum Subj. 2004 Summer (10) l-3. Pub Med PMID 15835026. 

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