1. A History of Human Research Protections and Institutional Review Boards Roger L. Bertholf, Ph.D. Associate Professor of Pathology Chair, University of Florida IRB-03 Roger L. Bertholf, Ph.D. Associate Professor of Pathology Chair, University of Florida IRB-03

2. The Nuremberg Trials The International Military Tribunal (1945) The Doctors Trial (1946) The Nuremberg Code (August, 1947) The International Military Tribunal (1945) The Doctors Trial (1946) The Nuremberg Code (August, 1947)

3. The Nuremberg Code Established necessity of informed consent Introduced concept of beneficence Introduced the notion of proportionality between risk and benefit Established necessity of informed consent Introduced concept of beneficence Introduced the notion of proportionality between risk and benefit

4. The Declaration of Helsinki Adopted by the World Medical Association in 1964 Provided guidelines for the conduct of human subjects research –Institutional Review Boards –“generally accepted scientific principles” –Distinction between clinical and basic research –Placebo controversy Adopted by the World Medical Association in 1964 Provided guidelines for the conduct of human subjects research –Institutional Review Boards –“generally accepted scientific principles” –Distinction between clinical and basic research –Placebo controversy

5. The Tuskegee Syphilis Study PHS initiated syphilis treatment program in 1928 Discovered 35 – 40% infection rate in Macon County, AL Revised study to observation only Enlisted help of the Tuskegee Institute Terminated in 1972 PHS initiated syphilis treatment program in 1928 Discovered 35 – 40% infection rate in Macon County, AL Revised study to observation only Enlisted help of the Tuskegee Institute Terminated in 1972

6. The Belmont Report Drafted by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research Final version adopted in 1979 Three sections: –Clinical practice vs. research –Three guiding principles of ethical research –Application of the three principles Drafted by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research Final version adopted in 1979 Three sections: –Clinical practice vs. research –Three guiding principles of ethical research –Application of the three principles

7. Clinical practice vs. research What is the purpose of the activity? Are results generalizable? Example What is the purpose of the activity? Are results generalizable? Example

8. Three Guiding Principles of Ethical Research Respect for Individuals Beneficence Justice Respect for Individuals Beneficence Justice

9. Respect for Individuals Individuals act as autonomous agents

10. 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. To show lack of respect for an autonomous agent is to repudiate that person’s considered judgments, to deny an individual the freedom to act on those considered judgments, or to withhold information necessary to make a considered judgment, when there are no compelling reasons to do so.

11. Respect for Individuals Individuals act as autonomous agents Individuals who are not capable of acting as autonomous agents are entitled to special protections –Minors –Mentally incapacitated persons –Prisoners Individuals act as autonomous agents Individuals who are not capable of acting as autonomous agents are entitled to special protections –Minors –Mentally incapacitated persons –Prisoners

12. Beneficence Guided by two basic principles: –Do no harm –Maximize benefits and minimize potential harms Risks should be in proportion to potential benefits Research design should ensure valid results Guided by two basic principles: –Do no harm –Maximize benefits and minimize potential harms Risks should be in proportion to potential benefits Research design should ensure valid results

13. Justice Benefits and risks of human research should be fairly distributed How do you select human research subjects? –Societal allocation of burdens and benefits –Equality, need, contribution, effort, merit Social vs. individual justice Benefits and risks of human research should be fairly distributed How do you select human research subjects? –Societal allocation of burdens and benefits –Equality, need, contribution, effort, merit Social vs. individual justice

14. The Informed Consent Complete disclosure of all procedures, any foreseeable risks, and any reasonably anticipated benefits Informed consent can be waived only if: –The risks are no greater than minimal –The research cannot be practically conducted if consent is required –Subjects are debriefed, when appropriate Complete disclosure of all procedures, any foreseeable risks, and any reasonably anticipated benefits Informed consent can be waived only if: –The risks are no greater than minimal –The research cannot be practically conducted if consent is required –Subjects are debriefed, when appropriate

15. The Informed Consent Proxy consent Intentional/unintentional coercion Information must be presented in a comprehensible manner Proxy consent Intentional/unintentional coercion Information must be presented in a comprehensible manner

16. Assessment of Risk/Benefits Research involving brutal or inhumane treatment is never acceptable Risks should be reduced to only those necessary to achieve the objective If there is risk of serious impairment, there must be extraordinary justification If vulnerable populations are used, there must be a specific reason for doing so Relevant risks must be included in the informed consent Research involving brutal or inhumane treatment is never acceptable Risks should be reduced to only those necessary to achieve the objective If there is risk of serious impairment, there must be extraordinary justification If vulnerable populations are used, there must be a specific reason for doing so Relevant risks must be included in the informed consent

17. Federal Regulations 45 CFR 46 –The Common Rule (Part A) –Subparts B, C, and D 21 CFR 50 and 56 –50 includes rules for clinical trials –56 describes IRB responsibilities 45 CFR 46 –The Common Rule (Part A) –Subparts B, C, and D 21 CFR 50 and 56 –50 includes rules for clinical trials –56 describes IRB responsibilities

18. The Multiple Project Assurance Any institution conducting federally funded (or regulated) research must provide the OHRP with a legally binding assurance that human research subjects are protected from unnecessary risk. –Single or Multiple –MPAs are usually approved for 5 years Any institution conducting federally funded (or regulated) research must provide the OHRP with a legally binding assurance that human research subjects are protected from unnecessary risk. –Single or Multiple –MPAs are usually approved for 5 years

19. The University of Florida MPA Provides for 4 IRBs: 01-04 (WIRB) Stipulates that all research at UF involving human subjects will be conducted in accordance with federal guidelines Provides for 4 IRBs: 01-04 (WIRB) Stipulates that all research at UF involving human subjects will be conducted in accordance with federal guidelines

20. Components of the UF MPA Institution is guided by the ethical principles in the The Belmont Report Specifies that IRBs will consider: –the risks to the subjects, –the anticipated benefits to the subjects and others, –the importance of the knowledge that may reasonably be expected to result, and –the informed consent process to be employed. Institution is guided by the ethical principles in the The Belmont Report Specifies that IRBs will consider: –the risks to the subjects, –the anticipated benefits to the subjects and others, –the importance of the knowledge that may reasonably be expected to result, and –the informed consent process to be employed.

21. Applicability of the UF MPA The UF MPA applies if any of the following conditions are met: –the research is sponsored by this institution, or –the research is conducted by or under the direction of any employee or agent of this institution in connection with his or her institutional responsibilities, or –the research is conducted by or under the direction of any employee or agent of this institution using any property or facility of this institution, or –the research involves the use of this institution's non-public information to identify or contact human research subjects or prospective subjects. The UF MPA applies if any of the following conditions are met: –the research is sponsored by this institution, or –the research is conducted by or under the direction of any employee or agent of this institution in connection with his or her institutional responsibilities, or –the research is conducted by or under the direction of any employee or agent of this institution using any property or facility of this institution, or –the research involves the use of this institution's non-public information to identify or contact human research subjects or prospective subjects.

22. IRB responsibilities The IRB-03 is administratively responsible to the President of this institution, who has delegated the responsibility to this institution’s Vice President for Research. (Dr. Win Phillips) This institution's IRBs have effective knowledge of subject populations, institutional constraints, differing legal requirements, and other factors which can foreseeably contribute to a determination of risks and benefits to subjects... The IRB-03 is administratively responsible to the President of this institution, who has delegated the responsibility to this institution’s Vice President for Research. (Dr. Win Phillips) This institution's IRBs have effective knowledge of subject populations, institutional constraints, differing legal requirements, and other factors which can foreseeably contribute to a determination of risks and benefits to subjects...

23. The Office for Human Research Protections (OHRP)