1.3 The Belmont Report (1979)

1.3 The Belmont Report (1979)

Origin and the National Commission

The third pillar of historical ethical guidance in the United States is the Belmont Report. In 1974, following the public exposure of the ethical violations in the Tuskegee Syphilis Study (which ran from 1932 to 1972 and withheld penicillin treatment from African American men to observe the natural progression of the disease), the U.S. Congress passed the National Research Act of 1974.

This legislation established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission was tasked with identifying the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects. After intensive deliberations, including a key meeting at the Smithsonian Institution's Belmont Conference Center in February 1976, the Commission released the Belmont Report on April 18, 1979. The Belmont Report remains the ethical foundation for U.S. human subject protection regulations, directly inspiring the Common Rule (45 CFR 46) and FDA regulations (21 CFR Parts 50 and 56).

Distinguishing Clinical Practice from Research

One of the primary tasks of the National Commission was to define the boundary between clinical practice and research. The Belmont Report notes that confusing these two concepts can lead to the therapeutic misconception, where a research subject mistakenly believes that the primary purpose of a clinical trial is to provide personalized medical care.

The Report defines the boundaries as follows:

• Clinical Practice: Refers to interventions designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success. The purpose of medical or behavioral practice is to provide diagnosis, preventative treatment, or therapy to specific individuals.
• Research: Designates an activity designed to test a hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, or statements of relationships). Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective.

If an intervention has an element of research (such as evaluating safety or efficacy), it must be submitted to IRB review, even if it is conducted in a clinical setting.

The Three Core Ethical Principles

The Belmont Report establishes three fundamental ethical principles that govern all human subjects research: Respect for Persons, Beneficence, and Justice.

1. Respect for Persons

Respect for persons incorporates two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy (such as children, prisoners, or individuals with cognitive impairments) are entitled to protection.

• An autonomous person is an individual capable of deliberation about personal goals and of acting under the direction of such deliberation.
• To respect autonomy is to give weight to autonomous persons' considered opinions and choices while refraining from obstructing their actions unless they are clearly detrimental to others.
• For individuals with diminished autonomy, protection must be put in place, which may include limiting their participation in risky research or requiring additional oversight (such as parent/guardian permission and child assent).

2. Beneficence

In the context of the Belmont Report, beneficence is not understood as a charitable act, but as an obligatory duty. Researchers treat persons in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being. The Belmont Report outlines two general rules that complementary express the principle of beneficence:

1. Do no harm (the Hippocratic maxim).
2. Maximize possible benefits and minimize possible risks.

Beneficence requires researchers and IRBs to systematically analyze the risks of a study and ensure they have been reduced to the minimum necessary to achieve the scientific objectives.

3. Justice

Justice raises the question of who ought to receive the benefits of research and bear its burdens. It is a principle of fairness in distribution. In the past, research was often conducted on vulnerable populations (such as institutionalized patients, prisoners, or poor clinic patients) because they were easily accessible, while the benefits of the research (such as new drugs or medical procedures) were primarily enjoyed by wealthier, privileged classes.

• Injustice occurs when some benefit to which a person is entitled is denied without good reason, or when some burden is imposed unduly.
• The principle of justice requires that the selection of research subjects be fair, ensuring that the burdens of research are not unfairly concentrated on specific socio-economic, racial, or institutionalized groups.

The Three Applications

The Belmont Report translates its three core ethical principles into three practical applications for clinical trial conduct: Informed Consent, Assessment of Risks and Benefits, and Selection of Subjects.

1. Application of Respect for Persons: Informed Consent

The consent process must contain three distinct elements:

• Information: The disclosure must include research procedure details, purposes, risks, anticipated benefits, alternative treatments, and the statement that the subject can withdraw at any time.
• Comprehension: The information must be presented in a language and format that matches the subject's capability. Investigators are responsible for ensuring that the subject has actually understood the information.
• Voluntariness: Agreement to participate must be free of coercion (threat of harm) and undue influence (offer of an excessive, unwarranted, or inappropriate reward to obtain compliance).

2. Application of Beneficence: Assessment of Risks and Benefits

The assessment of risks and benefits requires a careful gathering of systematic data about the proposed research:

• Risk refers to the possibility that harm may occur, encompassing physical, psychological, legal, social, and economic harm.
• Benefit refers to something of positive value related to health or welfare.
• The investigator and the IRB must determine whether the risks to subjects are reasonable in relation to anticipated benefits to subjects (if any) and the importance of the knowledge that may reasonably be expected to result.

3. Application of Justice: Selection of Subjects

The application of justice operates on two levels:

• Individual Justice: Researchers must exhibit fairness in selecting subjects. They must not offer potentially beneficial research only to favored patients or select only "undesirable" or vulnerable patients for risky research.
• Social Justice: Requires that distinction be made between classes of subjects that ought and ought not to participate in research, based on the ability of that class to bear burdens and on the appropriateness of placing further burdens on already burdened classes. For example, research should not be conducted on prisoners if the study could easily be conducted on non-imprisoned populations.