With all the buzz recently on regulatory reform for institutional review boards (IRBs), it’s worth looking back to the foundation of today’s human research protections. The guiding principles that shape IRB regulations were born from a call for change, much like the one driving the conversations happening today. They were crafted to allow flexibility and they remain essential, even as today’s research landscape is evolving.
A turbulent decade sets the stage for reform
To understand the Belmont Report, we need to return to the 1970s. In the U.S., it was a volatile period marked by advances in medical science and the public exposure of serious ethical issues in human research.
Following thalidomide and the Kefauver–Harris amendments of the 1960s, the 1970s brought rapid advances in medicine, including advances in medical imaging, the introduction of genetic engineering, new drugs and chemotherapy, and the beginning of preventative care. The same period also included the Vietnam War, the civil rights and women’s rights movements, Roe v. Wade, and Watergate. Together, these events reflected a broader recognition that change was needed.
The Supreme Court’s Roe v. Wade decision sparked public concern about the ethics of human experimentation. Senator Edward Kennedy’s congressional hearings highlighted unethical pharmaceutical testing involving infants and children. Other examples, including the Willowbrook study and Stanley Milgram’s work on obedience, further exposed ethical concerns. Perhaps the most widely known example was the examination and public exposure of the Tuskegee Syphilis Study.
The Tuskegee Syphilis Study exposes a breaking point
This study was a U.S. Public Health Service (PHS) study designed to observe the natural history of untreated syphilis. During the study, treatment for syphilis became available but was not offered to participants. Despite complaints from scientists, the study enrolled about 600 rural Black men and continued for more than 40 years. After a whistleblower alerted the press, The Washington Star and The New York Times exposed the study in July 1972. Following public exposure, the Centers for Disease Control (CDC) and PHS appointed an ad hoc advisory panel to review the study. That advisory committee recommended terminating the study in November 1972.
Congress responds with the National Research Act
Separately, Senator Kennedy was holding Senate Health Subcommittee hearings on human experimentation. Through those hearings, additional medical and ethical abuses came to light. Following the hearings, Congress introduced legislation that was signed into law on July 12, 1974. The Act increased funding for research, mandated research training for biomedical and behavioral research, required institutions to establish IRBs to review research, and empowered a national commission to make recommendations on the protection of humans in research.
This commission would be the first of its kind to function as more than an advisory body. Its recommendations were codified into law. The 1974 National Research Act, formally titled “An Act to amend the Public Health Service Act to establish a program of National Research Service Awards to assure the continued excellence of biomedical and behavioral research and to provide for the protection of human subjects involved in biomedical and behavioral research and for other purposes,” contained two titles:
- Title I: Biomedical and Behavioral Research Training
- Title II: Protection of Human Subjects of Biomedical and Behavioral Research
- Part A: Establishes a National Commission
This legislation established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission was directed to consider:
- The boundaries between biomedical and behavioral research and the accepted and routine practice of medicine.
- The role of assessment of risk–benefit criteria in the determination of the appropriateness of research involving human subjects.
- Appropriate guidelines for the selection of human subjects for participation in such research.
- The nature and definition of informed consent in various research settings.
The Commission drafts its report at Belmont Conference Center
In February 1976, the commission met at the Smithsonian Institution’s Belmont Conference Center for a four-day discussion. There, it formed the draft of what would later become the 1979 Belmont Report, formally titled “Ethical Principles and Guidelines for the Protection of Human Subjects of Research.” After nearly four years of monthly deliberations, the Report became a foundation for research ethics that continues to guide review and oversight of human subjects research today.
The Belmont Report was broader than the Nuremberg Code. It was designed to provide the basis on which rules could be formulated, criticized, and interpreted. Its objective was to offer an analytical framework for resolving ethical problems arising from research involving human subjects. In the preamble, the Report states, “By publishing the Report in the Federal Register, and providing reprints upon request, the Secretary intends that it may be made readily available to scientists, members of Institutional Review Boards, and Federal employees … Unlike most other reports of the Commission, the Belmont Report does not make specific recommendations for administrative action by the Secretary of the Department of Health, Education, and Welfare (DHEW, the predecessor of the Department of Health and Human Services [DHHS]). Rather, the Commission recommended that the Belmont Report be adopted in its entirety, as a statement of the Department’s policy.”
Why the Commission first had to define research
The Commission’s first charge was to define “research.” Until research was clearly distinguished from “practice,” it would be difficult to determine what required review. The Commission defined the “practice” of medicine as interventions designed solely to enhance well-being with a reasonable expectation of success. Practice is intended to provide diagnosis, preventative treatment, and/or therapy. By contrast, the Commission defined “research” as an activity designed to test a hypothesis and permit conclusions to be drawn. Research is intended to develop or contribute to generalizable knowledge, usually with an objective and a set of procedures designed to reach that objective. As a general rule, if an activity includes any element of research, that activity should undergo review.
Three basic principles guide the Report’s framework
The Report then outlined three basic principles: respect for persons, beneficence, and justice.
Respect for persons includes two ethical provisions: Individuals should be treated as autonomous agents, and people with diminished autonomy are entitled to protection. This principle encompasses informed consent. It requires that participants enter research voluntarily and with adequate information. It also requires consideration for people who are immature or incapacitated, with protections aligned to the risk of harm and likelihood of benefit.
Beneficence includes two general rules: Do no harm, and maximize possible benefits while minimizing harms. This principle can include conflict because learning what may be beneficial can require exposing people to risk. As a result, beneficence can involve difficult choices.
Justice addresses who should receive the benefits and bear the burdens of research. The report outlines several ways to think about justice, including:
- To each person an equal share.
- To each person according to individual need.
- To each person according to individual effort.
- To each person according to societal contribution.
- To each person according to merit.
At its core, justice requires a fair distribution of costs and benefits. The report does not dictate a single definition of these principles. Instead, it outlines ways to consider and apply them.
Informed consent requires information, comprehension, and choice
The Report further describes informed consent as a process that includes three core concepts: information, comprehension, and voluntariness:
- Information: What should be conveyed to a potential subject. The Report discusses both a prescriptive list of elements and a “reasonable person” standard, meaning what a reasonable person would want to know to decide whether to participate.
- Comprehension: How information is conveyed matters as much as the content itself. To the extent possible, an opportunity to choose should be provided even to those with diminished capacity.
- Voluntariness: Participation should be free from coercion and undue influence.
Assessing risks and benefits in human subjects research
The report also outlines the assessment of risks and benefits and provides context for what may be considered a risk:
- Risk and benefit assessment includes probability and magnitude:
- Probability: How likely is the risk or benefit to occur?
- Magnitude: How serious is the risk, or how meaningful is the benefit?
- Harms and benefits may be psychological, physical, legal, social, or economic.
- Risks and benefits may affect individuals, groups of individuals, or society at large.
- Minimum considerations include that brutal or inhumane treatment is never morally justified; risks should be reduced to those necessary to achieve the objective; significant risks must be justified; inclusion of vulnerable populations must be appropriate; and relevant risks and benefits must be addressed through the informed consent process.
Equitable subject selection reflects the justice principle
The report also describes the selection of subjects. Justice and equitable subject selection go hand in hand. Subject selection must be equitable and should not expose certain individuals or classes of individuals to unnecessary or disproportionate risk. Justice is relevant at two levels, individual and social:
- Individual justice includes fairness in selecting individual subjects.
- Social justice recognizes an order of preference for research participation and considers whether certain classes of subjects require additional safeguards before they can be included.
Even when individuals are selected fairly, injustice may still appear because of cultural biases.
The Report becomes the foundation for the Common Rule
Taken together, the Report became the basis for DHEW regulations. Further refinements continued, and the Food and Drug Administration (FDA) aligned with the Belmont Report in 1981. By 1991, several agencies had adopted the rule, and the “Common Rule” was established. These two sets of regulations (21 Code of Federal Regulations [CFR] 50 and 56, and 45 CFR 46) still reflect the foundation set by the Report in our regulatory requirement for approval.
The IRB shall determine all are met:
- Risks are minimized
- Risks are reasonable in relation to anticipated benefits
- Selection of subjects is equitable
- Informed consent will be sought
- Informed consent will be documented
- There are adequate provisions for monitoring data to ensure safety
- There are adequate provisions to protect privacy and confidentiality
When some or all participants are vulnerable, additional safeguards must be in place.
These provisions remain essential to human research protections. It’s amazing how the Report’s principles continue to provide a foundation for reviewing research. Their continued relevance reflects the care, rigor, and dedication of the Commission. To learn more, visit the Office for Human Research Protections (OHRP) website for videos and written testimony from interviews with Commission members and staff during the Report’s 25th anniversary celebration in 2004.
