IRB Member Training 2 Topics of Discussion o

IRB Member Training

2 Topics of Discussion o The Vice Chancellor for Research o The UCI IRB o The IRB: What to Know o The IRB Review Process o Resources

3 The Vice Chancellor for Research o Safeguarding the rights and welfare of human participants in research and other research activities is a general Institutional policy delegated by the Chancellor through the Vice Chancellor for Research. o The Vice Chancellor for Research is the Institutional Official. It is his responsibility to exercise appropriate administrative oversight to assure that UCI’s policies and procedures designed for protecting the rights and welfare of human participants are effectively applied in compliance with its Assurance. o At UCI, the Vice Chancellor for Research is Pramod Khargonekar, Ph. D.

4 The UCI IRB o The IRB is a committee of physicians, scientists, advocates and members of the community who come together to review research protocols. o The IRB has the oversight responsibility for protecting the rights and welfare of research participants. o The IRB Committees are required to have a minimum of five members each, with varying backgrounds and expertise to provide complete and thorough review of research activities commonly conducted by the Institution. o Each IRB Committee must include at least one member whose primary interests are in a scientific area, one member whose primary interests are in a non-scientific area and one member who is not affiliated with UCI (i. e. not a family member or spouse of an employee, not an active alumnus). o At least one non-affiliated member and one non-scientist are present at convened meetings. o Take a look at this OHRP video for membership requirements!

5 The UCI IRB • The IRB is responsible for ensuring that any research study conducted at the institution is appropriate and will not place participants at any undue risk of harm. • The IRB also reviews the procedures to be followed during the conduct of research to make sure that research participants are treated with dignity and respect. • Your expertise on the IRB is invaluable & will positively contribute to the review process!

6 The UCI IRB � UCI has four IRB Committees: • IRBs “A” and “B” review biomedical research • IRB “C” reviews social/behavioral research • IRB “E” reviews matters of non-compliance � UCI allows for the ability to rely on another IRB, including a commercial IRB

7 The UCI IRB o For greater than minimal risk research, full committee meetings are held monthly. o For minimal risk research, subcommittee meetings are held weekly. o Some Human Research Protections (HRP) staff are IRB members for processing straightforward, minimal risk transactions within the office. o For other transactions, such as personnel changes, non-IRB member HRP staff have been delegated authority to review and approve.

8 The IRB: What to Know The IRB considers these regulations: Federal § 45 CFR Part 46 – OHRP (includes pre and post 2018 Common Rule) § 21 CFR Parts 50 (protection of human subjects) and 56 (IRBs) – FDA § Health Insurance Portability and Accountability Act – HIPAA § Family Educational Rights and Privacy Act – FERPA § Protection of Pupil Rights Amendment – PPRA § Right to Try Act - RTT State § Health and Safety Code: Protection of Human Subjects in Medical Experimentation Act § Health and Safety Code: Consent for Minors § Health and Safety Code: Use of Death Data Records § Right to Try Act (more stringent requirements like IRB review) International § The European Union General Data Protection Regulation

9 The UCI IRB: What to Know o IRB Members take an additional CITI training module – designed specifically for their role. o Additional education is provided at each convened meeting. Typically, training relates to topics covered in that meeting’s agenda.

Criteria for IRB Approval 45 CFR 46. 111, 21 CFR 56. 111 BENEFICENCE JUSTICE Experimental Design Risk/Benefit Analysis Data Safety Qualifications of Researchers Subject Selection Inclusion/exclusion Recruitment Fair Distribution RESPECT FOR PERSONS Privacy & Confidentiality Vulnerable Populations Informed Consent Surrogate Consent Parent Permission / Assent

11 The IRB: What to Know § 46. 111 (DHHS) 56. 111 (FDA) 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 that are consistent with sound research design and that 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 (e. g. , the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility. • (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. The IRB should be particularly cognizant of the special problems of research that involves a category of subjects who are vulnerable to coercion or undue influence, such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons.

12 § 46. 111 (DHHS) 56. 111 (FDA) Criteria for IRB approval of research. The IRB: What to Know • (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. • (5) Informed consent will be appropriately documented or appropriately waived in accordance with § 46. 117. • (6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects. • (7) When appropriate, there adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

13 The IRB: What to Know § 46. 111 (DHHS) 56. 111 (FDA) Criteria for IRB approval of research. • • (8) For purposes of conducting the limited IRB review required by § 46. 104(d)(7)), the IRB need not make the determinations at paragraphs (a)(1) through (7) of this section, and shall make the following determinations: – (i) Broad consent for storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens is obtained in accordance with the requirements of § 46. 116(a)(1)-(4), (a)(6), and (d); – (ii) Broad consent is appropriately documented or waiver of documentation is appropriate, in accordance with § 46. 117; and – (iii) If there is a change made for research purposes in the way the identifiable private information or identifiable biospecimens are stored or maintained, there 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, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

14 The IRB: What to Know Required Elements of Consent* • A statement that the study involves research • An explanation of the procedures of the research • A description of the procedures to be followed & duration • 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. • A disclosure of appropriate alternative procedures or courses of treatment, if any • A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights A statement that participation is voluntary • • *Additional elements may apply

15 The IRB: What to Know New consent requirements per 2018 Rule • (9) One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens: – (i) A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or – (ii) A statement that the subject's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.

16 The IRB: What to Know Additional elements of informed consent (including new requirements per 2018 Rule) • • • (c) Additional elements of informed consent. Except as provided in paragraph (d), (e), or (f) of this section, one or more of the following elements of information, when appropriate, shall also be provided to each subject or the legally authorized representative: (1) 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) that are currently unforeseeable; (2) Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's or the legally authorized representative's consent; (3) Any additional costs to the subject that may result from participation in the research; (4) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject; (5) A statement that significant new findings developed during the course of the research that may relate to the subject's willingness to continue participation will be provided to the subject; (6) The approximate number of subjects involved in the study; (7) A statement that the subject's biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit; (8) A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions; and (9) For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i. e. , sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).

17 The IRB Review Process • • For each IRB Full Committee meetings, new studies, modifications and continuing review submissions will be added to the IRB agenda 3 weeks before the day of the meeting The IRB staff have one week to review up to 25 items – they will review submissions for regulatory and institutional requirements and send a pre-review (administrative review) to the lead researcher (LR) and their team The study team has one week to provide a response to the pre-review – this is optional – they may choose to not respond The IRB members have one week to review submitted materials – All documents are provided to the IRB electronically by 5 pm on Friday, a week before the meeting http: //apps. research. uci. edu/irbagenda/ – If IRB members may have questions, they could reach out to the IRB Administrative reviewer (listed on the 1 st page of the Reviewer Checklist) to convey their questions to the study team or they may choose to reach out to the researchers directly – please note that any new documents or new information should be provided a few days before the meeting

18 The IRB Review Process o If you are assigned as a Primary or Secondary Reviewer, you will need to complete the Reviewer’s Checklist. This document is uploaded in the e-agenda, along with all pertinent review materials, such as the Protocol Narrative, Consent Form, Master Protocol and Investigator’s Brochure. o The Checklist addresses elements of IRB approval and elements of consent. o Specific questions and concerns from Human Research Protection (HRP) Staff will be included for your response / comments. o Some special determinations will need to be made. This will be noted on the Checklist and the agenda. o Make sure all sections are complete; sign the checklist & hand to HRP Staff after the meeting. o Any questions prior to the meeting? Please contact HRP Staff (the IRB Administrator, Senior IRB Analyst).

19 The IRB Review Process

20 The IRB Review Process • The IRB reviews each protocol to ensure that the criteria for approval has been met. • The IRB has the authority to approve a protocol (aka “A”), require specific changes (aka “M” for minor changes – also known as approved with conditions), or table a protocol (aka “T”) when significant issues are noted. • The IRB may (rarely) disapprove a protocol. This occurs after significant effort has been made to work with the research team – to help the protocol meet criteria for IRB approval. Once disapproval occurs, not even the Vice-Chancellor for Research can overturn the IRB’s decision. • Conversely, the IRB may approve a protocol and the Vice-Chancellor for Research can disapprove.

21 The IRB Review Process: The Chairs • Biomedical Chairs: • Tahseen Mozaffar, MD • Kenneth Linden, MD, Ph. D • Social/ Behavioral / Educational Chair: • Elizabeth Cauffman, Ph. D

22 Resources At the Meeting: o o o Agenda IRB Chair IRB Members Laminated Sheets Help with Voting / Determinations HRP Staff! (at the meeting – or anytime…that’s what we are here for!) Other Resources: o ORA Website- page for IRB Members