1. Institutional Review Boards (IRBs), Informed Consent, and Responsibilities Requirement for IRBs -DHHS: 45 CFR Part 46 -FDA: 21 CFR 56 Requirement for and Elements of Informed Consent -DHHS: 45 CFR Part 46 -FDA: 21 CFR 50

2. Requirement for IRB Review 45 CFR 46 “In the case of any application submitted to the Secretary for financial assistance to conduct research, the Secretary may not approve or fund any application that is subject to review … by an Institutional Review Board …” 21 CFR 56 “… any clinical investigation … shall not be initiated unless that investigation has been reviewed and approved by … an IRB …”

3. Purpose of the IRB “[A] group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical [and behavioral] research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects.” “The local IRB at the research site is the cornerstone of the American system of protection of human subjects.”

4. IRB Membership > 5 members -varying backgrounds -professional competence to review specific research activities -diverse membership -one non-scientific member -one non-institutional member

5. IRBs (cont.) Review, require modifications to and approve all human use research -assess risk/benefit ratio -insure adequate informed consent Terminate/Suspend research -Risks/adverse events become excessive or outweigh benefits -non-compliance of investigator Conduct continuing review of the research Document all actions

6. Mandated Criteria for IRB Approval of Research Risks to the subjects are minimized -sound research design -risks are reasonable in relation to anticipated benefits -selection of subjects is equitable -informed consent obtained -informed consent documented -privacy and confidentiality protected -additional safeguards included to protect the rights and welfare of vulnerable populations

7. Special Protections Fetuses, Pregnant Women, and Human In Vitro Fertilization - Minimal risks to fetus/mother - Must meet health needs of fetus/mother Prisoners - Minimal risk/minor inconvenience - More than Minimal Risk with potential for benefit Children - Anticipated benefit - Solicit assent of the child/Consent of the parents

8. Regulatory Categories of Research Related Risk More than minimal risk - Clinical Trials with drugs or devices Minimal Risk - What you might expect to be done at a visit to your physician for a physical exam Exempt - Educational tests, surveys, interviews, observation of public behavior

9. IRB Requirements Related to Risk More than Minimal Risk - IRB Form (Blue Form) - Protocol - Informed Consent Document - IRB Review (Full Board) Initial Request Continuing Review

10. IRB Requirements Related to Risk Minimal Risk - IRB Form (Blue Form) -Protocol - + Informed Consent Document - + Expedited IRB Review - Initial and Continuing Review Exempt - Not recognized at UTMB - Handled as Expedited

11. Other Special Areas of Concern Genetic Testing/Research on blood or discarded materials -May be considered in the expedited category No identifiers No links to subjects -Referred for Full Board review Identifiers or links to subjects Risks of psychological harm or loss of confidentiality

12. Informed Consent of Human Research Subjects General Requirements: -Obtained from subject or subject’s legally authorized representative prior to enrollment. -Provides sufficient opportunity to consider whether or not to participate. -Minimizes coercion or undue influence. --subject reimbursement --finder’s fees

13. General Requirements (Cont.): -Written in an language understandable to the subject or subject’s representative. --written at an 8th (or lower) grade level --foreign language consent form -Contains no exculpatory language --cannot be asked to waive their legal rights or release the investigator, sponsor, or institution from liability Informed Consent of Human Research Subjects

14. Elements of Informed Consent Basic Elements: -Statement(s) that the study involves research, purpose of the research, expected duration of the subject’s participation, description of procedures, and identification of procedures which are experimental. -A description of any reasonably foreseeable risks or discomforts to the subject. -A description of any benefits to the subject or to others which may reasonably be expected from the research.

15. -A disclosure of appropriate alternative procedures or courses of treatment, if any, which might be advantageous to the subject. -A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained. -For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained. Elements of Informed Consent

16. -An explanation of whom to contact for answers to pertinent questions about the research and research subject’s rights, and whom to contact in the event of a research related injury to the subject. -A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. Elements of Informed Consent

17. Additional Elements (when appropriate): -A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable. -Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject’s consent. -Additional costs to the subject that may result from participation in the research.

18. -Consequences of the subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject. -A statement that significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject. -The approximate number of subjects involved in the study. Elements of Informed Consent

19. Informed Consent Documentation: -Written consent form previously reviewed and approved by the IRB -Signed by subject or legally authorized representative after having the opportunity to read the form and ask questions -Copy to the person signing the form (Except for TDCJ subjects) -Separate consent form for TDCJ subjects

20. IRB Waiver of written informed consent -If it is the only record linking the subject and the research; principal risk would be potential breach of confidentiality or -The research minimal risk and involves no procedures for which written consent is normally required outside of the research context. -The IRB may require the investigator to provide subjects with a written statement regarding the research Informed Consent

21. Informed Consent: Special Points Research requirements are different than clinical requirements Consent Form must be approved by the IRB (Prior to use) -Initially and at least annually during the continuing review process -Subject or representative* must have research procedures explained to them *Research must be approved by the IRB for non- consenting subjects No telephone consent

22. Waiver of Informed Consent for Emergency Research Regulations permit waivers -IRB can waive written consent --Minimal risk --Consent would provide link/confidentiality problem Amendment to Regulations in 1996 -IRB can waive consent requirements for More than Minimal Risk studies --Special/Stringent requirements

23. Responsibilities Institutional -Written assurance to NIH Office for Protection from Research Risks (OPRR) agreeing to comply with all applicable research regulations -Appoint an IRB -Provide sufficient space, facilities, resources and staff to ensure that the IRB can carry out its responsibilities

24. IRB -Follow written procedures for initial and continuing review -Provide oversight -Review and approve changes to research activities -Report incidents of non-compliance involving risks to subjects or any other serious or continuing non-compliance to OPRR -Suspend or terminate research activities when necessary Responsibilities

25. Investigator -Perform only IRB approved research activities -Assume front line position for risk minimization -Ensure true informed consent process -Document informed consent -Keep IRB informed -Keep records and copies of IRB correspondence Responsibilities

26. Results of Non-Compliance Local Audit Performed -IRB suspension of research activities -Notify funding agency of suspension -Probable loss of funding (temporary or permanent) OPRR/FDA Audit (Institution or investigator) -Suspension/restriction of research -Probable loss of funding -Placed on FDA “sanctions” list