New IRB Member Training Version December 2019 INTRODUCE

New IRB Member Training Version: December 2019

INTRODUCE ROLES, RESPONSIBILITIES AND EXPECTATIONS DEFINE SCOPE OF ROLE AS PART OF HRPP PROVIDE THE REGULATORY TOOLS NEEDED TO SERVE AS MEMBER IDENTIFY WHAT VERSION OF COMMON FEDERAL RULE TO APPLY TO RESEARCH EMPHASIZE THE AAHRPP STANDARDS TO BE MET AS AN ACCREDITED IRB NOTE: SOME MATERIAL FROM THIS PRESENTATION IS TAKEN FROM A WIRB COPERNICUS GROUP PRESENTATION “AAHRPP TRAINING: IRB MEMBERS AND CHAIR” BY REBECCA RUTSTEIN Overview Drexel University - Office of Research & Innovation 2

THE IRB The Institutional Review Board (IRB) is an administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated. Governed by federal rules and regulations that are meant to protect human research subjects: Common Federal Rule (45 CFR 46 (DHHS) and 21 CFR 56 (FDA) ) Drexel University - Office of Research & Innovation 3

What is Human Subject Research? The IRB does not follow the dictionary or common language definition of “human” or “research” but rather the federal definitions (namely from the Department of Health and Human Services (DHHS) and Food and Drug Administration (FDA)). Knowing these how these terms are defined allows the IRB to make a decision whether a project is human research or not human research This is decision is typically made by the IRB a designated reviewer. Investigators can submit for a “Letter of Determination” Drexel University - Office of Research & Innovation 4

What is “research”? DHHS (REVISED RULE) • Research – a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. FDA (does not follow REVISED RULE) • Research – any experiment that involves a test article and one or more human subjects, and that either: a) must meet the requirements for prior submission to the Food and Drug Administration; or b) the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for research or marketing permit. Drexel University - Office of Research & Innovation 5

What is “human”? DHHS (REVISED RULE ) FDA (does not follow the REVISED RULE) • Human subject – a living individual about whom an investigator (whether professional or student) conducting research: • 1. Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; • Or • 2. Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens. • Human subject – an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient. Drexel University - Office of Research & Innovation 6

Research Designation vs Research Procedures • Research activities involve any interventions or data collection that is being specifically performed for the investigation at hand. • Keep in mind the distinction between what qualifies as “standard of care”, “normal operations or activities being performed regardless of the investigation at hand” versus what is occurring specifically for research. • Sometimes the data being collected is identical to data that would have been created despite the investigation. In such a case the data collection itself would be the research component and not the activity that would have created the data. • The Board must consider the risks and ethical issues associated with each component of the research. Drexel University - Office of Research & Innovation 7

What are your responsibilities regarding the HRPP? Drexel University - Office of Research & Innovation Protect the rights and welfare of subjects Follow the policies and procedures 8

What are the ethical rules or guidelines you are expected to follow? The IRB is guided by the principles in the Belmont Report: Beneficence, Respect , and Justice The Belmont Principles are the basis for the worksheets and checklists used to approve research. Clinical trials will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with good clinical practice and the applicable regulatory requirements. Drexel University - Office of Research & Innovation 9

What are the rules or guidelines are IRB members expected to follow? Drexel University - Office of Research & Innovation HRP-010 POLICY HUMAN RESEARCH PROTECTION PLAN HRP-020 POLICY - IRB MEMBER REVIEW EXPECTATIONS HRP-106 SOP – COMMITTEE REVIEW CONDUCT HRP-400 WORKSHEET – CRITERIA FOR APPROVAL CHECKLISTS HRP-300 – HRP-313 WORKSHEETS HRP-402 – HRP-414 10

Checklists and Worksheets for IRB Members: All located on IRB Website • HRP-300 CHECKLIST - Waiver of Consent HHS. pdf • HRP-311 CHECKLIST - Wards. pdf • HRP-313 CHECKLIST - Non-Significant Risk Device. pdf • HRP-404 WORKSHEET - Short Form. pdf • HRP-405 WORKSHEET - Additional Criteria DOD. pdf • HRP-406 WORKSHEET - Additional Criteria DOJ. pdf • HRP-407 WORKSHEET - Additional Criteria ED. pdf • HRP-408 WORKSHEET - Additional Criteria EPA. pdf • HRP-307 CHECKLIST - Nonviable Neonates. pdf • HRP-409 WORKSHEET - Additional Criteria DOE. pdf • HRP-308 CHECKLIST - Prisoners. pdf • • HRP-309 CHECKLIST - Unexpected Incarceration. pdf HRP-410 WORKSHEET - Additional Criteria International. pdf • HRP-414 WORKSHEET - Adults Lacking Capacity. pdf • HRP-301 CHECKLIST - Waiver of Consent Emergency Research. pdf • HRP-302 CHECKLIST - Waiver of Consent Leftover Specimens. pdf • HRP-303 CHECKLIST - Waiver of Documentation of Consent. pdf • HRP-305 CHECKLIST - Pregnant Women. pdf • HRP-306 CHECKLIST - Neonates of Uncertain Viability. pdf • HRP-310 CHECKLIST - Children. pdf Drexel University - Office of Research & Innovation 11

What are the legal rules and guidelines you are expected to follow? These are outlined in section 2. 3 of the HRP-010 Policy – Human Research Protection Program All of the Worksheets and Checklists incorporate all legal requirements (both of the Pre-2018 and 2018 Final Rule). Drexel University - Office of Research & Innovation 12

Do I need to memorize all the rules and regulations? • No. This is not necessary. • Instead you should be generally familiar with the content. • It is more important that you know that the regulatory tools exist (the policies, forms, checklists, worksheets, guidance documents, and other references), know where to find them, and know how to apply them to the research. Drexel University - Office of Research & Innovation 13

What trainings are you expected to complete? All members must complete and maintain current certificates in the following CITI courses: • Human Research (Medical and Social/Behavioral Research) • Health Information Privacy & Security (HIPS) • Good Clinical Practice • Conflict of Interest Drexel University - Office of Research & Innovation 14

Expectations for participation (First of 3): ACTIVELY ATTEND ALL MEETINGS WHENEVER POSSIBLE Drexel University - Office of Research & Innovation Asked to kindly respond to Doodle polls and other correspondence in a timely manner Asked to let IRB staff know in advance if unable to attend Failure to attend creates issues with quorum and affects balance of roster 15

Primary and secondary presenters are responsible for presentation and to help facilitate discussion Expectations for Participation (Second of 3): BE FULLY PREPARED TO DISCUSS ALL AGENDA ITEMS All members Must have read all agenda items with criteria for approval, ethical and scientific considerations, and institutional and professional knowledge in mind Encouraged to reach out to the Investigator to gather information, other IRB members, the Chair, and IRB staff members ahead of meeting for assistance about agenda items When consulting with PI avoid making recommendations as final decisions will come from consensus vote at Committee meeting Drexel University - Office of Research & Innovation 16

Expectations for participation (Third of 3): BE ACTIVELY ENGAGED AT THE MEETING Drexel University - Office of Research & Innovation Everyone is encouraged to speak up, share, confer, debate, and otherwise support the discussion of the topic at hand Remember Board decisions are made by vote and consensus approval. 17

Expectations for Confidentiality: Drexel University - Office of Research & Innovation All members must have signed and must abide by the Drexel University Institutional Review Board Member Confidentiality and Non-Disclosure Agreement Unless otherwise specified, the terms of the agreement remain place even after membership is completed 18

Who is responsible for the Human Research Protection Program (HRPP)? Organization Official- Aleister Saunders Chief Compliance Officer and Institutional Official- Kairi Williams Director of Human Research Protections Plan- Gabrielle Rebillard Fundamentally YOU AND EVERYONE (IRB and COI staff, Research Teams, Etc. ) Drexel University - Office of Research & Innovation 19

Out of Scope for IRB Member Decisions and Tasks Who is Responsible Determination of engagement IRB staff and Chair Determination that project requires IRB review IRB Staff and Chair How decisions and determinations are communicated to researchers IRB Staff and Chair (when indicated) Quality improvement activities for the IRB Staff and QA/QI Analyst Review of roster of IRB Members IRB staff and Chair Lapses in IRB approval IRB Staff handles this (Clinical trials- also Chair) Communication with investigators after meeting IRB Staff (and Chair or IRB member at the request of the Fully Convened Committee) Drexel University - Office of Research & Innovation 20

Who reports unanticipated problems , allegations or evidence of non-compliance, suspensions or terminations and to whom? Anyone can report these items Reports that rise to the level of the following are reviewed by the convened IRB: Unanticipated problems involving risks to subjects or others Serious or continuing non-compliance Suspensions and terminations of IRB approval Kairi Williams or designee makes determination IRB decides how to protect subjects When appropriate - reported to appropriate external offices such as regulatory agencies, sponsors, sites, and CCO Drexel University - Office of Research & Innovation 21

Which version of the Common Rule applies? • Research approved before January 21, 2019 follows the pre -2018 Common Rule • FDA regulated research • DOJ regulate research Drexel University - Office of Research & Innovation • Research approved after January 21, 2019 follows the Final Rule (2018 Common Rule) 22

Think of the Common Rule as the floor not the ceiling for compliance standards. We aim not to just comply with but also to exceed standards for your research and research subjects. Drexel reviews all research as though it were federally regulated. Drexel University - Office of Research & Innovation 23

Reviews and Conflict of Interest • Policy- Definitions (HRP-001) “ 2. 8 <Conflicting Interest>: An IRB member or consultant has a conflicting interest if any of the following are true for the member/consultant or an individual in the member’s <Immediate Family>: • Involvement in the design, conduct, or reporting of the research, • Equity interest <Related to the Research>, exclusive of interests through mutual funds, • Compensation <Related to the Research> in the preceding 12 months, • Proprietary interest <Related to the Research>, including copyrights, or patents, trademarks, • Any other reason for which the IRB member believes that he or she cannot be objective. ” • Policy: IRB Member Review Expectations HRP -020 • “ 2. 2 For each review consider whether you have a <Conflicting Interest> • 2. 2. 1. Know the definition of <Conflicting Interest> • 2. 2. 2. If you have a <Conflicting Interest>, do not participate in that review (including discussion or voting) except to provide information requested by the IRB. Drexel University - Office of Research & Innovation 24

Types of submissions reviewed at IRB Full Committee Meetings Drexel University - Office of Research & Innovation INITIAL APPLICATIONS MODIFICATIONS TO ALREADY APPROVED RESEARCH CONTINUING REVIEWS REPORTABLE NEW INFORMATION RESPONSES TO ANY OF THE ABOVE WHERE PROTOCOL HAD PREVIOUSLY BEEN CONDITIONALLY APPROVED OR DEFERRED OTHER: SUSPENSIONS, TERMINATIONS, HUDS 25

More about Reportable New Information (RNI) Broad group of categories that represent important information that for IRB but which does not fit into other submission types Included are FYI-sort of items, but also timely reports related to topics such subject safety and research non-compliance Worksheet: New Information HRP 411 Describes actions that can be considered in response to RNIs Drexel University - Office of Research & Innovation 26

According to Policy: Definitions (HRP-001) Section 2. 32 • Minimal Risk: The probability and magnitude of harm or discomfort anticipated in the research that are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests ( according to Section 2. 32 How is Risk Defined? And 2. 32. 1. • The IRB interprets the phrase “Ordinarily encountered in daily life or during the performance of routine physical or physiological examination or tests” to refer to normal healthy individuals in general and exclude the risks that certain subcategories of individuals face in their everyday life. For example, the IRB does not evaluate the risks imposed in research focused on a special population against the inherent risks encountered in their work environment (e. g. , emergency responder, pilot, soldier in a combat zone) or having a medical condition (e. g. , frequent medical tests or constant pain). • Drexel University - Office of Research & Innovation 27

Review of Federally Sponsored Projects Criteria in worksheets must be met and in the consent the sponsor must be named and included as agency/party that can inspect and copy research records Federal • HRP-405 WORKSHEET - Additional Criteria DOD. pdf • HRP-406 WORKSHEET - Additional Criteria DOJ. pdf • HRP-407 WORKSHEET - Additional Criteria ED. pdf • HRP-408 WORKSHEET - Additional Criteria EPA. pdf • HRP-409 WORKSHEET - Additional Criteria DOE. pdf Other federal agencies • FDA • Ex: labeling requirements for investigational product • NIH • Certificate of Confidentiality details Drexel University - Office of Research & Innovation 28

Criteria from sponsors Drugs or devices Specific Review Types Emergency Use HUD Compassionate or Expanded Access Vulnerable Populations Drexel University - Office of Research & Innovation 29

Review of Studies that involve drug(s) When a study involves a drug, what process do you follow to make sure that the drug either has an IND number or meets the criteria to be exempt from an IND? • If review conducted under expedited process • IRB staff and chair responsibility What communications with the research pharmacy are required by your policies and procedures when the research involves a drug? • All investigational drugs must go through the pharmacy! • If review conducted by Fully Convened IRB • HRP-420 WORKSHEET - Regulatory Review • HRP-425 WORKSHEET - Drugs Drexel University - Office of Research & Innovation 30

When a study involves a device, what process do you follow to make sure that the device either has an IDE number, meets the abbreviated IDE requirements or meets the criteria to be exempt from an IDE? • Handled by IRB staff, members and Chair • HRP-420 WORKSHEET - Regulatory Review • HRP-426 WORKSHEET - Devices Drexel University - Office of Research & Innovation 31

Emergency Use Worksheet: Emergency Use Drugs and Biologics (HRP-451) Worksheet: Emergency Use Devices (HRP-452) Drexel University - Office of Research & Innovation 32

Humanitarian Use Device HUDs typically do not involve research. In fact, other than the HUD holder the physicians using the HUD must attest that they are not conducting research (i. e. cannot collect data or manipulate use). As such HUDs are one exception to the IRB reviewing investigations that are not human research Drexel University - Office of Research & Innovation 33

Compassionate Use or Expanded Access and Humanitarian Use Devices Drexel University - Office of Research & Innovation 34

What about research with vulnerable populations? • One of the revisions to the Final Rule concerns “vulnerability” as having more to do with context and less about membership in specific population categories • The Preamble to the Final Rule defines vulnerability as “vulnerable to coercion and undue influence refers to the ability to make an informed decision about participating in research” and • The Final Rule does not list pregnant women and handicapped or mentally disabled persons but instead lists “individuals with impaired decision-making capacity” Drexel University - Office of Research & Innovation 35

The Checklists for Children (HRP-310), Pregnant Women (HRP-305), Prisoners (HRP 308), Neonates (HRP-306 and 307) still apply But there are still The Worksheet: Adults Lacking Capacity (HRP-414) still applies and The IRB remains responsible for helping to ensure compliance with all requirements for informed consent and related protections for coercion and undue influence Drexel University - Office of Research & Innovation 36

What happens when someone informs you that he or she plans an emergency use of a test article in a lifethreatening situation? Drexel University - Office of Research & Innovation Handled by IRB staff and chair IRB chair • Use HRP-180 SOP - Emergency and Compassionate Uses • Use: HRP-451 WORKSHEET - Emergency Use Drugs and Biologics; or • HRP-452 WORKSHEET - Emergency Use Devices. pdf 37

Identify any (potential) criteria international, federal, state and local rules, laws and applicable guidance, institutional and HRPP standard operating policies applicable to project as well as AHHRPP accreditation standards Ensure compliance standards for the same are met Goals of Review Make editorial comments only for purposes of study design, internal logic, and readability of documents Ensure all study documents are accurate, complete and mirror one another where appropriate Ensure comments and determinations are justified, referenced and documented by the standards mentioned above (HRP Policies, SOPs, Forms, Checklists, Worksheets and Templates, and Investigator Guidance) Version: June 2019 38

Know where to find and when to apply: CFR (pre-2018 and Final Rule) ICH Goals of Review Forms, Worksheets, Checklists and Policies State and local laws Basic research methods and requirements • Scientific method • Research design approaches • Research misconduct • Principles of data quality and integrity • Data quality • Data Integrity Version: June 2019 39

Help with reviews Encouraged to reach out to other Board members, IRB staff, colleagues (keeping confidentiality agreement intact), external resources All HRPs needed to do reviews are on website; special checklists and worksheets will be provided with agenda packet as appropriate Agenda with reviewers are sent to members one week before meeting in order to allow time to reach out to others and complete review prior to meeting. Drexel University - Office of Research & Innovation 40

Strategies for doing a review There are no validated “right” or “wrong” way to review so long as all goals are met. Drexel University - Office of Research & Innovation 41

More review tips: • One recommended method is to start with reading consent as though you are a naïve, prospective subject. What do you think the project is? • Ask for help when you aren’t sure you have the expertise, don’t know what criteria are applicable, struggling to understand the protocol, have a potential conflict of interest, etc. … • Read through protocol document at a high level to get an overall sense of the project and then dive in for specific details, to check continuity and accuracy/consistency with other study documents • Review what is included in application AND what is missing. • Remember to take breaks. It helps to take a fresh look at the project. • It is often helpful to reach out to the researcher or the research team directly. Conversations add a lot to the review! Drexel University - Office of Research & Innovation 42

Some Additional Resources • https: //www. hhs. gov/ohrp/educationand-outreach/human-researchprotection-programfundamentals/resources-for-irbmembers/index. html • https: //www. hhs. gov/ohrp/regulations -and-policy/regulations/commonrule/index. html • https: //www. fda. gov/home • http: //www. aahrpp. org/ Drexel University - Office of Research & Innovation 43