Background and Principles
Background for Development of Human Research Participants Protections
Examples of inhumane and unethical treatment of humans in the name of research have been documented throughout recent history. The Nuremberg trials documented the unethical behavior of Nazi physicians, but there have been serious ethical lapses in the United States as well. American researchers from the Public Health Service studied 400 African American men with syphilis in the Tuskegee syphilis study between 1933 and 1972. These men were not asked for their informed consent to be in the study and they were, in fact, given misinformation about their participation. Even after penicillin became available and was known to be effective in the treatment of syphilis in the 1950s, it was withheld from these subjects because the researchers were interested in the natural history of the disease. The study only ended when a journalist broke the story of the study. In another example, researchers from Harvard and MIT formed a "science club" of 19 mentally impaired boys at the Fernald State School between 1946 and 1956. These boys were fed forms of radioactive iron or calcium, sometimes in their milk, to enable the researchers to study the body's ability to digest minerals. Doctors at the Jewish Chronic Disease Hospital conducted studies of human transplant rejection using cancer cells. The subjects were not asked for informed consent or told that they were being injected with live cancer cells. Between 1963 and 1966, children at the Willowbrook State School, a state school for "mentally defective" youths, were purposely infected with the hepatitis virus in a study of that disease. During the course of this study the institution closed its doors to new clients, claiming overcrowding. However, the wing housing the hepatitis program was willing to admit new clients if their parents agreed to allow their children to participate in the ongoing studies.
Behavioral and social science researchers have exposed other humans to severe trauma and psychological stress in investigations of power. The participants in Milgram's "obedience" studies, conducted in the early 1960s, were told that they had to continue to participate in the study and shock another person at increasingly intense voltages. Studies supported by the Human Resources Research Office of the U.S. Army introduced severe stress to Army recruits by threatening them with death from errant artillery rounds or by causing the recruits to think that they, by making a mistake in wiring an instrument, had caused the injury or death of others in their units. Despite potentially important knowledge gained from such studies, the risks to the participants were extreme.
Codes of Research Ethics
Codes of research ethics have been developed, in part to address the disregard for human safety and dignity that these research projects reflect. The Nuremberg Code of 1947 was the first international code of research ethics. Its first principle is "The voluntary consent of the human subject is absolutely essential." The accompanying text made it clear that this voluntary consent should also be informed consent: "...the person involved ... should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision." This principle of "free and informed consent" remains the basic foundation of ethical research with human participants.
Another early code was the Helsinki Declaration, adopted by the World Medical Association at its meeting in Helsinki, Finland in 1964. Its second principle, "The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol which should be transmitted for consideration, comment and guidance to a specially appointed committee independent of the investigator and the sponsor..." established the concept of ethical review.
The first ethical code covering social and behavioral research was a set of 10 ethical principles adopted by the American Psychological Association in 1972. The bases for these principles were critical incidents. Psychologists were asked to submit examples of research that they deemed unethical or of questionable ethicality. The committee charged with developing ethical standards for psychological research then developed principles that would guide the conduct of researchers when engaging in research that could pose ethical problems. The American Psychological Association's principles were the first to recognize the principle of confidentiality. Principle 10 states: "Information obtained about the research participants during the course of an investigation is confidential. When the possibility exists that others may obtain access to such information, ethical research practice requires that this possibility, together with the plans for protecting confidentiality, be explained to the participants as a part of the procedure for obtaining informed consent." Most professional organizations have ethical codes, and most require authors of manuscripts submitted to the journals of these organizations to state that they have followed these ethical principles in their research.
The U. S. Department of Health, Education, and Welfare issued ethical guidelines in 1971 which were codified into Federal Regulations in 1974 as 45 CFR 46. This central set of regulations is known as the Common Rule, because most other federal agencies also rely on them as the primary set of requirements related to IRB operations and research review. However, the primary impetus for current government ethical regulation began with the establishment of a National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research under the aegis of the Department of Health, Education, and Welfare in 1974. The Commission was charged with identifying the basic ethical principles that should underlie research with human subjects. The report of the Commission, called The Belmont Report because it was based on deliberations held at the Smithsonian Institution's Belmont Conference Center, was published in 1979.
Belmont Principles
The Belmont Report identified three basic ethical principles that now serve as the foundation for all human research participant protection programs. They are:
- Respect for Persons (autonomy): This principle acknowledges the dignity and freedom of every person. It requires obtaining informed consent from all potential research subjects (or their legally authorized representatives). It also obligates researchers to protect those with limited autonomy.
- Beneficence: This principle requires that researchers maximize benefits and minimize harms or risks associated with research. Research-related risks must be reasonable in light of expected benefits.
- Justice: This principle requires the equitable selection and recruitment and fair treatment of research subjects.
General Principles of IRB Review
The IRB is responsible for protecting the rights of human participants engaged in research. This is achieved through a careful review of the proposed study, including the scientific design, methodology, study procedures, participant population, recruitment procedures, and consent processes. Through this review, the IRB seeks to balance the risks to the participants against the scientific knowledge to be gained and the potential benefits to society.
Federal guidelines grant the IRB autonomy in the interpretation of regulations for review of research studies. Thus, each IRB must apply its own discretion when deciding how a research proposal will be judged to meet the ethical criteria provided in the regulations. And, in the case of informed consent, 45 CFR 46 allows the IRB to waive the requirement for written consent in special circumstances. This means that each IRB must independently determine the nature of research risks and research benefits, the extent to which risks to participants are "reasonable" in relation to anticipated benefits, when research risks and benefits justify modification of the informed consent requirement, and what constitutes equitable participant selection.
No involvement of human participants in research, including initial contact and recruitment, is permitted until the IRB has reviewed and approved the planned procedures. It is the responsibility of the investigator to obtain approval from the IRB prior to the initiation of any research, including recruitment activities and pilot or pre-test studies.
IRB review is grounded in the following essential principles for participant rights and protections:
All activities involving humans as research participants must provide for the safety, health, and welfare of every individual. Rights, including the right to privacy, must not be infringed. No participant in a research activity shall be exposed to unreasonable risk to health or well-being.
An individual does not abdicate any rights by consenting to be a research participant. A participant has the right to withdraw from a research project at any time or can refuse to participate without loss of benefits to which the subject would otherwise be entitled. Further, a participant has the right to receive appropriate professional care, to enjoy privacy and confidentiality in the use of personal information, and to be free from undue embarrassment, discomfort, anxiety, and harassment.
The direct or potential benefits to the participant, or the importance of the knowledge to be gained, must not preclude consideration of the inherent risks to the individual.
The confidentiality of information received from participants shall be fully protected, both during and after the conduct of a research activity, when confidentiality is appropriate, within the limits of the law.
Participation in projects must be voluntary. Informed consent must be obtained from all participants and must be documented (unless the requirement for documentation of consent is specifically waived by the IRB). Methods in accordance with the requirements of 45 CFR 46.116 and 45 CFR 46.117, appropriate to the risks of the research, must be used to obtain the participants’ informed consent.
In research involving more than minimal risk or substantial stress or discomfort, such risk, stress, or discomfort shall be carefully explained to the participant before his or her participation and justified by the expected benefits of the research. The investigator shall be satisfied that the explanation has been understood by the participant, and the written consent of the participant (unless otherwise waived by the IRB), containing the substance of the explanation, shall be obtained and kept as a matter of record for 3 years after the conclusion of the study.