The Belmont Report Presentation for IRB Members

Historical Perspective • Nuremberg War Tribunal (1947) - Criminal proceedings against 23 leading German physicians and administrators for their willing participation in war crimes and crimes against humanity. Horrifying procedures were conducted for research purposes on thousands of concentration camp prisoners without their informed consent. • Syphilis Study in Tuskegee, GA (1932 -1972) – As part of a research project conducted by the U. S. Public Health Service, 600 low-income African-American males, 400 of whom were infected with syphilis, were monitored for 40 years. Free medical examinations were given; however, participants were not told about their disease. Even though a proven cure (penicillin) became available in the 1950 s, the study continued until 1972 with participants being denied treatment. In some cases, when participants were diagnosed as having syphilis by other physicians, researchers intervened to prevent treatment. Many participants 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.

Historical Perspective • Thalidomide use - Thalidomide was used in the 1950 s to combat unpleasant symptoms associated with pregnancy. At the time it was being used it was not usually disclosed to patients that the drug was investigational and still in the testing phase of the regulatory process. After women in Europe, Canada, and the U. S. were treated with the drug it was discovered that the drug had teratogenic effects, causing severe deformities in the fetus. Thalidomide was soon banned worldwide. Unfortunately, approximately 12, 000 babies were born with severe deformities due to thalidomide. • Radiation experiments (1940 s – 1960 s) - U. S. officials studied the effects of radiation through experiments on hospital patients, pregnant women, mentally disabled children, and enlisted military personnel. Few of the participants of the experiments gave informed consent; most had no knowledge that they were being subjected to radioactive materials. Manhattan Project officials authorized the wartime experiments to establish health and safety standards for the thousands of workers in atomic bomb plants.

Response to Research Abuses • Nazi atrocities in World War II drew attention to the lack of international standards on research with human participants and led to the formulation of the Nuremburg Code (1948). • The thalidomide disaster led to the adoption of the "Kefauver Amendment" (1962) to the Food, Drug and Cosmetic Act, requiring drug manufacturers to prove to the FDA the safety and effectiveness of their products and physicians to obtain informed consent from potential subjects before administering investigational medications. • The Declaration of Helsinki drafted by the world Medical Association in 1964 (most recently updated in 2000) builds on the Nuremberg Code and is the basis for Good Clinical Practices used today. • The National Research Act (1974) passed primarily in response to the syphilis study, codified the requirement that human participants in research must be protected and set the stage for the issuance of the Belmont Report.

National Research Act (1974) • Due to the publicity from the Syphilis Study, the National Research Act of 1974 was passed. • The National Research Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. • The Commission charge was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human participants and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research • Carrying out its charge, the Commission prepared the Belmont Report in 1979. • The Belmont Report is a statement of basic ethical principles and guidelines that provide “an analytical framework to guide the resolution of the ethical problems arising from research with human subjects. ” • The framework of the Belmont Report is presented in three discussion topics: boundaries between practice and research; basic ethical principles, and applications.

Boundaries between Practice and Research • The distinction between practice and research is blurred; often because they occur together. • The IRB must ensure that the researcher (and the participant) distinguishes practice from research in both social science and biomedical research • Minimize the potential for therapeutic misconception – when one believes the purpose of clinical research is to treat rather then to gain knowledge

Basic Ethical Principles • Respect for Persons – Individuals should be treated as autonomous agents – Individuals with diminished autonomy are entitled to protections • Beneficence – Do not harm – Maximum possible benefits, and minimize potential harms • Justice – Fair distribution of burdens and benefits of research

Respect for Persons • Treat individuals as autonomous persons; allow individuals to choose for themselves • Persons with limited autonomy need additional protection, even to the point of excluding them from activities that may harm them. The extent of protection should depend upon the risk of harm, and the likelihood of benefit. • The judgment that any individual lacks autonomy should be periodically re-evaluated, and will vary across situations.

Beneficence • The IRB should determine whether the risks to subjects are reasonable in relation to anticipated benefits • Obligations of beneficence affect both the researcher and society – § investigators are required to give forethought on maximization of benefits and reduction of risk that may be involved in the research § society should recognize the longer term benefits and risk that may result from the improvement of knowledge, and from the development of novel medical, psychological, and social processes and procedures

Justice • Treat people fairly • Do not exploit those who are readily available or malleable • Fair distribution of the risks and the benefits of research based upon the problem/issue under investigation

Applications of the General Principles • Consideration of the three general principles in the conduct of research lead to the consideration of: § Informed Consent process § Risk/Benefits assessment § Selection of research participants

IRB Members should consider the following…

Application of Respect for Persons • Informed Consent Process § Information - Does the consent form provide all the information necessary for the individual to make a reasoned decision? § Comprehension - Is the consent form crafted in language understandable to the potential participant? § Voluntariness - Does the consent form and clearly indicate that participation in the research is voluntary? § What additional protections can be in place to protect those with limited autonomy? § How to determine whether one lacks the autonomy to make a reasoned decision?

Applications of Beneficence • Assessment of Risks and Benefits § Risk refers to the probability of harm; when considering risk, one should consider both the probability and the severity of the envisioned harm; while the term, benefit refers to something that promotes health, well-being, or welfare. § What are the risks of harm to the participants (consider physical, psychological, social, and economic harms)? Are the risks justified? Can they be minimized? § Can the research design be improved to minimize risk and maximize benefit? § What are the benefits (to the participant; to society)?

Applications of Justice • Selection of Subjects § Is the potential subject pool appropriate for the research? § Is it appropriate to involve vulnerable populations (e. g. , economically disadvantaged; limited cognitive capacity) in the research or are they being enrolled because it is convenient or because they are easily manipulated as a result of their situation? § Are the recruitment procedures fair and impartial? § Are the inclusion and exclusion criteria fair and appropriate?

The Belmont Report • Although never officially adopted or endorsed by Congress or DHEW (now DHHS), the Belmont Report has served as an ethical framework for protecting human subjects for over 25 years. Many of it recommendations have been incorporated into DHHS Title 45 CFR Part 46 and FDA Title 21 CFR Part 50. • To obtain a full appreciation of the Belmont Report, IRB Members are strongly encouraged to read it in its entirety. The report can be found @ http: //www. fda. gov/oc/ohrt/IRBS/belmont. html

Questions? Please contact: § Karen Allen Director of Research Protections @ kallen@uci. edu or 949 -824 -1558