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Human Subjects Working Group Spring Workshop May 7 th , 2008. Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP) Division of Education and Development Lyndi Lahl, MS, RN Michelle Feige, MSW. Overview. OHRP’s QIP Assurance of Compliance

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Human Subjects Working Group Spring WorkshopMay 7th, 2008

Department of Health and Human Services (HHS)

Office for Human Research Protections (OHRP)

Division of Education and Development

Lyndi Lahl, MS, RN

Michelle Feige, MSW

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  • OHRP’s QIP

  • Assurance of Compliance

  • IRB Membership

  • Investigator Responsibilities

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OHRP’s QI Program (QIP)

  • OHRP initiated QIP 2002 to assist institutions in assessing and improving their human research protections program

  • QIP includes two separate components:

    • A Guided Self Assessment Tool

    • OHRP QA Consultation – Division of Education and Development staff

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Goals of OHRP’s QIP

  • Provide tools to help an institution identify strengths and areas for improvement

  • Provide detailed review of IRB written procedures and meeting minutes

  • Clarify regulatory requirements

  • Explore ways to improve the quality, efficiency, and effectiveness of the human research protection program

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Attributes of OHRP’s QIP

  • Voluntary

  • No Cost

  • Choice of components:

    1) independent self assessment

    • online guided self assessment tool

      2) consultation with OHRP

    • modes of interaction: on-site visit, videoconference or teleconference

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QA Self Assessment Tool

  • EVALUATES: Human Research Protection Program

    • General information about the program including organizational structure

    • Disclosure and management of conflicts of interest

    • Handling noncompliance

    • Workload of the IRB, staffing and resources

    • General information about the IRB

    • Education of Chair, members, staff, & investigators

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QA Self Assessment Tool

  • EVALUATES: The Institutional Review Board

    • Review process

    • Minutes

    • Post IRB review processes

    • Approval

    • Written procedures

    • Submission process for IRB review

    • Preparation for full committee review

    • Preparation for continuing review

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Why Seek an OHRP QA Consultation?

  • A site has made improvements to their HRPP and seeks an OHRP consultation to assess the current status of their program

  • A site has reached the level of continuing quality improvement of their HRPP and plans to seek accreditation

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Agenda for an On-Site Consultation


  • Interviews

    - Institutional Official

    - IRB members, Chair(s)

    - IRB office director(s), administrator,


    - Investigators

  • Records review

    - Written policies & procedures & IRB minutes

    - Research protocol files

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Agenda for an On-Site Consultation


  • Detailed review of written procedures, IRB minutes, and IRB records

  • Question and answer period

  • Exit interview with Institutional Official

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Agenda for a Video/Teleconference Consultation

  • Detailed records review

    • Written policies & procedures and

      IRB minutes

  • Limited interaction with personnel

  • Debriefing of Institutional Official & staff

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Frequently Discussed Topics

  • IRB written procedures

  • IRB minutes

  • Continuing review

  • Expedited review, use of exempt categories

  • Informed consent: documentation of waiver

  • IRB review of adverse events for multicenter trials

  • Review of Subparts B, C, D

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How the OHRP QA Team Handles Noncompliance

  • Procedural non-compliance

    - QA team clarifies regulatory requirements and works with institution to develop its corrective action plan

    - QA team may offer a follow-up interaction

  • Serious or systemic noncompliance that has or may put the rights and welfare of subjects at risk

    - Same Steps as above

    - Recommend self-reporting to OHRP

    - Notification of Institutional Official & OHRP


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Key Points OHRP’s QIP

  • Available to all institutions engaged in HHS conducted or supported nonexempt human subjects research

  • Various methods of conducting consultation

  • Helps institution to identify areas to improve current human research protections progarm

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HHS Regulations (45 CFR part 46)

HHS will conduct or support non-exempt

human subject research only if:

  • the institution has an OHRP-approved assurance, and

  • the institution has certified to HHS

    • research was reviewed and approved by IRB, and

    • the research will be subject to continuing review

      §46.103(b) & (f)

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Institution is Generally Engaged in Human Subjects Research

  • When employees or agents obtain, for research purposes:

    • data about the subjects of the research through intervention or interaction with them; or

    • identifiable private information about them

      §46.102(d) & (f)

  • Draft Guidance at:

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Institutions Generally Engaged, Examples:

  • Administer research interviews or questionnaires

  • Perform invasive or non-invasive procedures

  • Manipulate a subject’s environment

  • Receive or access identifiable private information

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Institutions Generally Not Engaged, Examples:

  • Release individually identifiable private information/specimens to another institution

  • Permit investigators from another institution to use their facilities for research

  • Provide information about research to prospective subjects

  • Perform commercial or non-collaborative service

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Institutional Responsibilities

Protect Human Subjects in Research

Responsibilities shared by

Institutional Officials, IRBs, and Investigators

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Institutional Assurance

  • Documentation of institution’s commitment to comply with applicable regulations §46.103(b) & (f)

  • Generally recognized by other federal departments & agencies

  • Method of compliance oversight for OHRP

  • Federalwide Assurance (FWA) – only assurance option

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Assurance Applications – Extending FWA

  • Individual Investigator Agreement

    • independent investigators

    • investigators at another institution

  • Assured institution responsible for oversight of research

    Sample agreement and guidance available

    at the OHRP website

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IRB Authorization Agreement

  • Detail which institution responsible for:

    • project(s) that will be reviewed by external IRB

    • monitoring and oversight

  • Consider including details on termination of agreement

  • Signed by each institution’s authorized official

  • Document kept by institutions – must be made available to OHRP, if requested

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FWA Covers

Institutional components

Institution’s employees and agents, including students

Under limited circumstances, FWA may be extended to individual investigators

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Assurance Applications - Relying on External IRB

Institution responsibility

  • Written agreement

    • IRB authorization agreement

  • Ensure research conducted per IRB approved plan

  • Procedures for reporting to OHRP

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Institutional Official’s Responsibilities

Assure compliance with the:

Terms of the Federalwide Assurance

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Institutional Official’s Responsibilities (cont’d)

  • Set the "tone" for an institutional culture promoting ethical conduct of research

  • Support IRB actions & determinations

  • Ensure that investigators fulfill their responsibilities

  • Support training/education opportunities for staff

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Additional Administrative Considerations

  • Applicability of assurance

  • Staffing and support

  • Administrative conflict of interest

  • Review by additional committees

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Key PointsAssurance of Compliance

  • There are many institutional responsibilities when engaged in human subjects research

  • OHRP holds FWA-holding institution responsible for compliance

  • Read and understand the terms of FWA assurance

  • Protecting human subjects is a shared responsibility

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  • Minimum of 5 members

  • Experience and Expertise

  • Diversity of Members

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Regulatory Membership Requirements

  • Minimum one scientist member

  • Minimum one non-scientist member

  • Roles of scientist vs. non-scientist

  • Minimum one nonaffiliated member

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Special IRB Members

  • Prisoner representatives

  • Alternate members

    • identify pairing of alternate and primary member(s)

    • appropriate expertise

    • substitute for entire meeting or any portion of meeting

  • Expert Consultant

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IRB Member Conflict of Interest

  • Investigators on the protocol, financial conflict, other

  • Conflicted members do not contribute to the quorum

  • May provide information requested by the IRB

  • Recusal from IRB’s deliberations and voting

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IRB Membership Selection & Retention

  • Who makes selection

  • Length of tenure

  • Reasons for termination

  • Retention strategies

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IRB Roster (IRB Registration)

Members identified by:

  • Name

  • Earned degree

  • Representative capacity

  • Indication of experience

  • Employment or other relationship between member and institution


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Key PointsIRB Membership

  • Meet regulatory membership requirements

  • Alternate member paired to primary member

  • IRB member conflict of interest must be addressed

  • Update IRB Roster with OHRP

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Protecting Human Subjects is a Shared Responsibility





Research Team






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Investigator Responsibility #1

Comply with relevant

Federal regulations

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Regulations for Protection of Human Subjects 45 CFR part 46

  • Subpart A – basic HHS Policy - “The Common Rule” or Federal Policy

    • Other federal departments & agencies have adopted

  • Subpart B - Pregnant Women, Human Fetuses, and Neonates

  • Subpart C - Prisoners

  • Subpart D - Children


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Investigator Responsibility #2

Recognize when the

regulations apply

to planned activities

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Materials Submitted to the IRB

  • Protocol, grant proposal, informed consent(s)

  • Recruitment materials and plan

  • Any IRB mandated or other related documents

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Understand IRB expectations and policies

Provide sufficient information and materials

Recognize and manage conflicts of interest

Comply with IRB decisions and requirements

Respond to IRB requests in a timely fashion

Considerations for IRB Review and Approval

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Investigator Responsibility #4

Prospective IRB review of proposed changes to research

No Changes to Research Without IRB Review and Approval

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Continuing Review

  • Status Reports

  • Lapse in Continuing Review

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Investigator Responsibility #6

Obtain and document legally effective informed consent, assent, and parental permission in accord with §46.116 and applicable subpart(s) and as approved by the IRB.

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Investigator Responsibility #7

Realize your role when reporting certain incidents

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What is an Unanticipated Problem?

Incident, experience, or outcome that is:

  • Unexpected (nature, severity, frequency)

  • Related or possibly related to research, AND

  • Suggests greater risk of harm than previously known or recognized

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Investigator Responsibility #8

Fulfill responsibilities when study is completed

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Study Completion

  • When is the study completed?

  • Responsibilities for study completion?

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Key Points Investigator Responsibilities

  • Follow Belmont Report, Federal regulations, IRB & institutional procedures and policies

  • Promptly report changes to the IRB

  • Obtain, document, and retain legally effective informed consent

  • Ensure ongoing protections

  • Understand role when reporting incidents to OHRP

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Human Subjects Working Group MeetingMay 7th, 2008

The Office for Human Research Protections

Lyndi Lahl, MS, RN

Michelle Feige, MSW

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  • Required written procedures

  • Additional considerations

    • Written procedures

    • IRB records

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7 Required Written Elements

  • “Magnificent 7” required elements & operational procedures

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Required Elements of

Written IRB Procedures


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Required Element 1

Procedures IRB will follow for conducting

initial review of research


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Required Element 2

Procedures IRB will follow for conducting

continuing review of research


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Initial & Continuing Review

Description of

  • Method of review

  • Reviewer system

  • Documents received and distributed for review

  • IRB review, findings, & determinations

  • Range of possible actions by IRB

  • Further review by institution

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Method of Review

  • Convened IRB Meeting

  • Expedited

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Convened IRB Meeting

  • Convened meeting (telephone, videoconference participation OK)

  • Quorum

    • majority of IRB members present

    • at least one non-scientist present

  • Approval by majority present

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Expedited Review

  • Minor changes to previously approved research

  • No greater than minimal risk and on “list” at 63 FR 60364-60367

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Expedited Review (cont’d)

Description of

  • Assignment of reviewers

    • IRB chair designates

    • criteria for assignment

    • IRB chair or experienced IRB member reviews

  • Documents distributed for review

  • Communication of approval action to all IRB members

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Reviewer System

Primary or other reviewer system

  • Initial review

  • Continuing review

  • Review of protocol changes

  • Review of required reports

  • Documents distributed for review

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Primary Reviewer System

  • Assignment of reviewer(s)

    • criteria for assignment

    • who assigns reviewer(s)

  • Responsibilities of primary reviewer(s)

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Documents for Initial Review

  • Protocol summary and/or full protocol

  • Proposed informed consent document

  • Relevant HHS application or proposal

  • Recruitment and data collection materials

  • Multi-center trials (HHS supported)

    • complete approved protocol and informed consent document

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Documents for Continuing Review

  • Protocol summary and/or full protocol,

    • include modifications previously approved

  • Current informed consent document

  • Status report:

    • number of subjects accrued

    • summary of unanticipated problems, available AE information, withdrawal of subjects, & complaints

    • literature summary, amendments, & modifications since last review

    • relevant multi-center trial reports

  • All other documents available

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Document Distribution- Convened IRB Review

No primary reviewer system

  • One member -- HHS proposal

  • All members -- all other materials

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Document Distribution- Convened IRB Review (cont’d)

Primary reviewer system

  • One member -- HHS proposal

  • Primary reviewer(s) -- all other materials

  • All other members receive summary of protocol, informed consent document, and recruitment materials (continuing review to also include status report)

  • Complete documentation available to

    all members

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IRB Review, Findings, & Determinations

Description of process:

  • Criteria for approval under §46.111 & applicable subparts

  • Informed consent considerations

    • basic & additional elements§46.116(a & b)

    • altering or waiving§46.116(c or d), §46.408(c), & §46.101(i)

    • waiving written documentation§46.117(c)

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Range of Possible IRB Actions

Description of action:

  • Approve research

  • Require modifications in order to secure approval

  • Disapprove research (convened IRB only)

  • Suspend or terminate previously approved research

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Documentation of IRB Review Process

OHRP recommends institutions have

written procedures for documenting

IRB findings, determinations, actions,

and other IRB requirements.

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Further Review by Institution

  • Who is responsible for further review

    • institutional committees, e.g., COI, Privacy Board, Radiation, Biosafety

    • other

  • Institutional policies relevant to review

  • Actions that may be taken by institution

    • institution may notoverride IRB disapproval

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Required Element 3

Procedures the IRB will follow for reporting

its findings and actions to the investigator

and the institution


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Reporting IRB Actions

To investigator

  • Written communication

  • Request for modifications or clarifications

  • Reviewing and acting upon investigator’s response

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Reporting IRB Actions (cont’d)

To institution

  • Written communication

  • Which institutional official(s) notified

  • How notification accomplished

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Required Elements 4

Procedures the IRB will follow for determining which projects require review more often than annually


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Determining Frequency of IRB Review

  • Specific criteria used to make these determinations

  • Document approval period

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Required Elements 5

Procedures the IRB will follow for determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review


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Verifying No Changes Since IRB Review

Specific criteria, e.g.,

  • Random selection of projects

  • Complexity of project

  • History or concerns re: investigator compliance

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Required Element 6

Procedures for ensuring prompt reporting to the IRB of proposed changes in a research activity and ensuring that such changes in approved research may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to the subject§46.103(b)(4)(iii)

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Ensuring Protocol Changes Made in Accordance with Regs

  • Steps to ensure compliance, e.g.,

    • training programs for investigator,

    • specific directives included in approval letters to investigators,

    • random or targeted audits of research

  • Exception - eliminate apparent immediate hazards to subjects

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Required Element 7

Procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, the Department or Agency head, and OHRP of any

  • unanticipated problems involving risks to subjects or others

  • any serious or continuing noncompliance

  • any suspension or termination of IRB approval §46.103(b)(5)

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Reporting Requirement

  • Who is responsible for prompt reporting

    • to whom/which office(s) or official(s)

  • Time frames for accomplishing reporting requirement

  • Range of possible actions taken by the IRB in response to reports

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OHRP Guidance

  • Reporting Incidents to OHRP:

  • Reviewing and Reporting Unanticipated Problems … and Adverse Events:

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Key PointsRequired Elements of Written IRB Procedures

  • Institutions must have written procedures comprised of the seven required elements

  • Include step-by-step operational details that are user friendly and effective

  • Implement throughout the organization

  • OHRP guidance is available

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Subparts B, C, and D

  • Categories of permissible research

  • Research not otherwise approvable (Secretarial panel process)

  • Additional criteria for IRB approval

  • Special requirements for informed consent, parental permission, and assent

  • Other considerations

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Informed Consent Process

  • Facilitate informed consent

  • “Long” and “short-form” consent options and considerations

  • Methods for ensuring use of proper informed consent document

  • Who may be/must be involved in consent process

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Informed Consent Process (cont’d)

  • Other considerations

    • distinguish between “informed consent” and “documentation” of informed consent

    • IRB’s role in monitoring informed consent process

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Ensuring IRB Knowledge of Local Context

  • Methods for ensuring IRB knowledge of local research context

  • See guidance document at:

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Other Relevant Authorities

  • Other Federal laws/regulations

  • State & local laws/regulations

  • Foreign laws/regulations/regulatory standards

  • Other

    • institutional commitments & policies

    • funding entities

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Determining Applicability and Exemptions


  • Institutional locus (e.g., IRB office)

  • Institutional person – someone with good foundation of human subjects’ protection regulations

  • Mechanism for ensuring no changes in research

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Lapse in Continuing Review

  • Notification of investigator that IRB approval has lapsed

  • Process used by IRB to determine whether individual subjects’ continued participation is in their best interest

  • Generally not reported to OHRP

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Conflict of Interest (COI)

  • Recognize

  • Manage

    HHS guidance on Conflict of Interest:

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Institutional Educational Requirements

Training and education program considerations

for IRB members, investigators, & staff

  • Who

  • How often

  • Documentation

  • Resources

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Other Issues for Possible Inclusion

  • Important definitions

  • Preparing for review/meeting

  • IRB meeting attendance

  • IRB fees

  • IRB member responsibilities

  • External IRB

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Other Issues for Possible Inclusion (cont’d)

  • Investigator responsibilities

  • Handling allegations of non-compliance

  • Maintenance of IRB records and meeting minutes

  • Emergency research

  • Description of FDA-related responsibilities

  • Institution-specific practices

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IRB Records

  • Copies of

    • research proposals reviewed

    • scientific evaluations, if any

    • approved sample consent documents

    • progress reports submitted by investigator

    • reports of injuries to subjects


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IRB Records (cont’d)

  • IRB meeting minutes

  • Records of continuing review activities

  • Correspondence between IRB and investigators


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IRB Records (cont’d)

  • List of IRB members

  • Written IRB procedures

  • Statement of significant new findings provided to subjects§46.115(a)(5-7)

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IRB Meeting Minutes

  • Regulatory requirements - §46.115(a)(2)

  • Objective

  • Too much or too little: It’s always a balancing act!

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IRB Meeting Minutes to Describe

Regulatory requirements

  • Attendance

  • IRB actions

  • IRB vote

  • Basis for requiring changes in or disapproving research

  • Controverted issues

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Attendance at Meeting

  • Document attendance

    • members

    • others

  • Entry/Exit/Recusals

  • Document quorum

  • Loss of quorum = no further IRB action

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IRB Actions and Votes

  • Minutes to reflect actions taken by convened IRB

    • regulatory

    • institutional

  • Vote on IRB actions

    • voting for

    • against

    • abstaining

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Basis for Requiring Changes in or Disapproving Research

  • Why IRB required changes to specific proposed research

  • Why IRB disapproved research

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Controverted Issues

  • Written summary

    • discussion and

    • resolution

  • Dictionary definition of controverted:

    - to dispute or oppose by reasoning

    - to engage in controversy

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Remember: Waiver of Informed Consent

Alteration or waiver of informed consent must be documented under §46.116(c) & (d)

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Additional Considerations

If you think documentation will enhance your IRB’s decision-making process when reviewing research…

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Considerations for Documentation

  • Consider documenting each IRB finding, determination, and requirement - including protocol-specific information justifying each decision

    • in the minutes of the IRB meeting (or, e.g., checklists, reviewer sheet)

    • alternative documentation for expedited review

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Considerations for Documentation (cont’d)

Protocol-specific information justifying the IRB’s

decision re:

  • Waiving written documentation of informed consent §46.117(c)

  • Approving research

    • criteria and rationale under §46.111

    • criteria and rationale under applicable subpart(s)

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Considerations for Documentation (cont’d)

Protocol-specific information justifying the IRB’s

decision re:

  • Approval period

  • Requiring modifications in research

  • Disapproving research

  • Suspending or terminating IRB approval

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Retention of IRB Records

  • Minimum three years

  • Accessible for inspection and copying


  • Check state and local laws

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Key PointsAdditional Considerations

  • Many institutions develop comprehensive procedures that go beyond what is required

  • Provide helpful resource for all involved in human subject research

  • Maintain records in compliance with regulations

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OHRP Contact Information

  • Website:

  • Email: [email protected]

  • Toll-free phone #: 1-866-447-4777

  • Main phone #: 240-453-6900

  • Join Listserv: