1. Institutional Review Board (IRB) What is our Purpose and Role for Ethical Research

2. Historical Development of the IRB

3. Nuremberg Code War Crime Trials Standards War Crime Trials Standards Voluntary consent/withdrawal at any time Voluntary consent/withdrawal at any time Degree of risk not outweighed by human importance Degree of risk not outweighed by human importance Experimental design to protect Experimental design to protect Termination of experiment at any stage if continuation is likely to result in injury, disability, or death Termination of experiment at any stage if continuation is likely to result in injury, disability, or death

4. Declaration of Helsinki Adopted June 1964 Adopted June 1964 Biomedical Research to Improve Biomedical Research to Improve Diagnostic Diagnostic Therapeutic and Therapeutic and Prophylactic procedures Prophylactic procedures Improve Understanding Improve Understanding Etiology and Etiology and Pathogenesis of disease Pathogenesis of disease

5. Belmont Report Adopted April 18, 1979 ethical principles and guidelines for the protection of human subjects Adopted April 18, 1979 ethical principles and guidelines for the protection of human subjects Three basic (primary) ethical principles Three basic (primary) ethical principles Respect for persons (Autonomy) Respect for persons (Autonomy) Beneficience—treated in an ethical manner Beneficience—treated in an ethical manner Justice Justice

6. Respect for Persons Persons should be treated as autonomous agents Persons should be treated as autonomous agents persons with diminished autonomy are entitled to protection persons with diminished autonomy are entitled to protection

7. Beneficence Do no harm Do no harm Maximize possible benefits and minimize possible harms Maximize possible benefits and minimize possible harms sometimes research subjects are not direct beneficiaries sometimes research subjects are not direct beneficiaries

8. Justice Developed from the Tuskegee syphilis studies of the 1940s, whereby rural black men were denied effective treatment to chart the untreated course of the disease even though it was not confined to that population Developed from the Tuskegee syphilis studies of the 1940s, whereby rural black men were denied effective treatment to chart the untreated course of the disease even though it was not confined to that population Who ought to receive the benefits of research and bear its burdens? Benefits and burdens of research to be distributed fairly Who ought to receive the benefits of research and bear its burdens? Benefits and burdens of research to be distributed fairly Mentally retarded children housed at the Willowbrook State School in Staten Island, New York, were intentionally given hepatitis in an attempt to track the development of the viral infection. The study began in 1956 and lasted for 14 years. The researcher also wanted to determine the effectiveness of gamma globulin injections as protection against hepatitis. They justified their deliberate infections and exposures by claiming that given that there was a high rate of infection in the institution it was practically inevitable that the children would become infected Mentally retarded children housed at the Willowbrook State School in Staten Island, New York, were intentionally given hepatitis in an attempt to track the development of the viral infection. The study began in 1956 and lasted for 14 years. The researcher also wanted to determine the effectiveness of gamma globulin injections as protection against hepatitis. They justified their deliberate infections and exposures by claiming that given that there was a high rate of infection in the institution it was practically inevitable that the children would become infected

9. Federal Regulations HHS Title 45 CFR 46 The Protection of Human Subjects HHS Title 45 CFR 46 The Protection of Human Subjects Office of Human Research Protections (OHRP) Office of Human Research Protections (OHRP) Common Rule Common Rule FDA Title 21 CFR 50, 54, 56, 312, 314 International Committee on Harmonisation (ICH) Guidelines International Committee on Harmonisation (ICH) Guidelines Good Clinical Practice Good Clinical Practice

10. IRB Makeup Minimum of 5 members Minimum of 5 members At least one community member At least one community member Varying backgrounds Varying backgrounds Scientific and Non-scientific Scientific and Non-scientific Sufficiently qualified through experience and expertise Sufficiently qualified through experience and expertise Meet the needs of studies reviewed Meet the needs of studies reviewed Must be nondiscriminatory Must be nondiscriminatory

11. 45 CFR 46.111 45 CFR 46.111 Criteria for IRB Approval of Research (a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied: (1) Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes. (2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

12. 45 CFR 46.111 45 CFR 46.111 Criteria for IRB Approval of Research (3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons. (4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by §46.116.§46.116 (5) Informed consent will be appropriately documented, in accordance with, and to the extent required by §46.117.§46.117

13. 45 CFR 46.111 45 CFR 46.111 Criteria for IRB Approval of Research (6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects. (7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. (b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

14. Questions?