VA Research: IRB and R&D Approval ProcessFrom Initial Submission, Through the Informed Consent Process and Continuing Review, To

Inactivation

Kimberly Summers, PharmDDeputy ACOS for Research

South Texas Veterans Health Care SystemResearch & Development Service

Overview

• What needs IRB Approval?• Types of Review• How to Submit New Application• Principal Investigator Responsibilities• Summary

When is STVHCS R&D Approval Needed?

• R&D Committee approval is required to conduct any and all VA research

• What constitutes VA research?

Definition of VA Research• Research sponsored by the VA• Research conducted using any property or facility of

STVHCS• Research conducted by or under the direction of any

salaried or without compensation (WOC) employee of the STVHCS during and in connection with her/his STVHCS responsibilities

• Funds for the research activities are managed by the STVHCS or Biomedical Research Foundation of South Texas

• Research which recruits subjects at the STVHCS or uses the STVHCS's nonpublic information to identify or contact human research subjects for research purposes (i.e. CPRS)

Types of IRB Review

• Not research or research not involving “human subjects”

• Human research eligible for exemption• Human research (non-exempt) eligible for

expedited IRB review• Human research (non-exempt) that is not

eligible for expedited review and must be reviewed by a convened meeting of the IRB (full IRB board review)

Types of IRB Reviews That Require STVHCS R&D Approval

• Research NOT involving “human subjects”• Human research eligible for exemption• Human research (non-exempt) eligible for

expedited IRB review• Human research (non-exempt) that is not

eligible for expedited review and must be reviewed by a convened meeting of the IRB

Non-Human Research

• Form available on IRB website • Obtaining aggregate data only with no

identifiable information• Form I required

– Person releasing the information has access to that information as part of their routine duties

– Person releasing the information verifies all information provided is de-identified

• Still requires R&D submission

Types of IRB Reviews That Do NOT Require STVHCS R&D Approval

• IRB determined to NOT be research– Quality Improvement Projects– Case reports– Meta-analysis of published studies

• May still require Privacy Officer approval– Any VA sensitive information– Personal Health Information is NOT allowed– Mary Wohl (VA ext 15602; marywohl@va.gov )

Training Requirements

IRB Required Training

• All investigators and research staff conducting human research at institutions using the HSC IRB must complete research ethics training provided by the University of Miami, Collaborative IRB Training Initiative (CITI).

• Details on IRB website - http://research.uthscsa.edu/irb/training.shtml

• The VA does not recognize the IRB CITI investigator training

R&D Required Training• The VA requires completion of a different CITI

investigator training course– Must complete the VA training if conducting VA

Research– The HSC recognizes the VA CITI training– Must be taken annually

• Information Security 201 for R&D Personnel– One time only

• Training required to maintain VA appt– VA Cyber Security Awareness– VHA Privacy Policy Web Training– Must be taken annually

VA Research Privileges are Required in Addition to Training

Requirements

Research Privileges

• Research credentialing and privileges are required prior to work on any VA protocol

• Requirements are different for the following groups– VA Employees – Fellows, Residents, and Students– Non-VA investigators or study personnel– Exempt study staff

http://www.southtexas.va.gov/research/

Exempt Personnel

• Study personnel who are not physically conducting research on VA property, only have access to de-identified data and/or not directly working with research subjects – Examples: lab personnel, data or administrative

personnel• Requirements

– VA Data Security 201 Training– Memorandum from PI denoting what their role in the

study will be  – Conflict of Interest Form        

Submission Process

IRB Protocol Submission

IRB Submission Form K

• Pre-Notification of the Intent to Conduct Research that includes other Institutions

• Required to submit with your IRB application

• Notifies the R&D office of your intent to conduct VA research

• R&D office signs Form K and returns with link to VA Research website

http://www.southtexas.va.gov/research/

R&D Submission

• Submit a hard copy of all required forms with appropriate signatures

• Original + 7 copies required• All study related documents and required

forms must also be submitted electronically on a CD

R&D Submission Date• Submission prior to the first Monday of each month

– Will be reviewed at the following month’s R&D meeting if all forms are completed and administrative stipulations addressed

• Protocols requiring review by a convened IRB– One of the following must have occurred prior to

application submission to the R&D office• IRB administrative review• IRB final resubmission • Final IRB approval

• Protocols eligible for IRB expedited or exempt review– Application submission to the R&D office should be

concurrent with IRB submission

R&D Administrative Review

• An appointment with the investigator and/or study coordinator is required to address any administrative stipulations

• The intent of the meeting is to address, correct, and finalize any administrative stipulations in real time to shorten the overall approval time

• Any changes required on IRB forms or informed consents can be incorporated into final IRB submissions, addressed at IRB admin review, or must be submitted as an IRB amendment

R&D Final Approval

• All administrative stipulations must be addressed and resubmitted at least one week prior to the R&D Committee Meeting for the protocol to be placed on the agenda– IRB approval may still be pending at the time of

resubmission• Final R&D approval can be granted following R&D

Committee review when:– IRB approval is in place– All R&D Committee stipulations have been addressed

IRB and R&D Initial Submission Summary

Full IRB Board Review Protocols

Exempt and Expedited Protocols

R&D Approval Timelines

BASELINE

R&D REVIEWS SINCE JAN 2009

Time from IRB approval until R&D approval

Median 72 days 34 days

Time from R&D meeting until R&D approval

Median 89 days 26 days

STVHCS R&D Approval

• Must have R&D approval letter prior to any of the following being conducted at the VA– Recruitment – Obtaining informed consent– Enrollment– Providing patient follow up

• An IRB approval letter does NOT constitute R&D approval

Informed Consent Process

• An IRB approved and stamped VA Informed Consent document does NOT constitute R&D approval

• IRB approved and stamped informed consent required– ONLY the most recent IRB approved and stamped

consent form can be used to consent subjects

• Documentation in the medical record required• Scanning of IC document required

Continuing Review and Protocol Modifications

Amendments & Modifications• Changes in previously approved studies

cannot be made without prior IRB review– Except when necessary to eliminate

immediate hazards to a subject• Examples of changes requiring IRB approval

– Number subjects consented and enrolled– Design, methods or procedures– Study staff, study sites/locations– Consent procedures, consent document– Recruitment advertisements, payments

Amendments and Modifications

• PI is responsible for submission to the IRB• STVHCS R&D office is notified by the IRB

– All studies identified as VA Research• IRB and R&D reviews are combined• Any required changes by the IRB or R&D

are forwarded by the IRB to the PI• Corrective actions are required prior to

IRB approval and initiation at the STVHCS

Changes in Personnel

• Personnel list submitted to IRB– IRB Form B-2– VA Form Personnel List for Human Studies

• For personnel engaged in research conducted at the VA– IRB will verify with the R&D office that all

study personnel have submitted the required documentation and been assigned research privileges at the VA prior to approval of the amendment

Continuing Review• IRB may approve a study for a period of no

longer than 1 year• For re-approval, the IRB must review the

protocol, any amendments, and a status report including: – Number of subjects accrued– Description of adverse events, unanticipated

problems, withdrawal of subjects, complaints

– Summary of relevant information– Copy of current consent document(s)

Continuing Review Process

• Continuing Review of Research Protocols form must be submitted to the VA R&D office– Contains VA specific information in addition to IRB

continuing review form– Submission of the IRB continuing review form and/or

approval letter to the R&D office is NOT required– R&D office staff coordinate with IRB continuing review

team for VA required changes• Exempt research

– IRB requires updates every 3 years– VA continuing review form required at least annually

Continuing Review Process

• Protocol approval at the STVHCS will expire if– Continuing review is not completed – Training requirements for the PI are not up-to-date at

the time of continuing review• Co-investigators and other study personnel will be removed

from active protocols if training requirements are not up-to-date

• Expiration of approval will be corrected upon receipt and satisfactory review and approval of the required documentation

Reporting Requirements

Unanticipated Problems Involving Risks to Subjects or Others

• Any incident, experience or outcome that meets all of the following criteria– Unexpected (in terms of nature, severity, or

frequency)– Related or possibly related to participation in the

research– Suggests that the research places subjects or

others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized

• May be an adverse event or non-adverse event• Events reported to the IRB related to VA research are

communicated to the R&D and vice versa

Reporting Noncompliance• Conducting research in a manner that disregards or

violates federal regulations, failure to follow the IRB requirements & determinations, or institutional policies and procedures – In the case of VA research includes the requirements

of the VA Handbook 1200.5• Handled by governing IRB• Findings of serious or continuing noncompliance

reported to:– OHRP– FDA if IND/IDE – ORO (VA Office of Research Oversight)

Protocol Inactivation

Inactivation of IRB Approval• When is it appropriate to inactivate IRB approval?

– Enrollment of new subjects is permanently closed– Data, private information, and/or clinical specimens are no

longer being collected for research purposes (including long term follow up)

– Subjects are no longer being treated under the research protocol (includes no plan for future research treatment)

– Research assessments or procedures are no longer being performed (includes no plan for future research procedures)

– Federal research funding for this study is closed– If a multi-center study where UTHSCSA is the study

operations center or the UTHSCSA investigator is the Lead Investigator, if the study closed at all participating sites

– Data/specimen analysis has been completed locally, or if analysis continues locally and the data has been permanently de-identified

Inactivation of R&D Approval

Specific IRB Questions

• Expedited review new studies:– Rhonda Barnard, MS, CIP 210-567-2372

• Full Board review new studies:– Debbie Etter, Team Leader 210-567-2356

• Modifications/Amendments– Helen Cavazos, Team Leader 210-567-2353

• Progress or Final reports:– Clara Perkins, Team Leader 210-567- 3086

Specific R&D Questions

• New study submissions and modifications/amendments for VA pending studies :– Angela Casas, (210)617-5300 VA ext 15523

• Progress or final reports and modifications/amendments for VA approved studies:– Tracy Jackson, (210)617-5300 VA ext 15520

Questions?

Kimberly Summers, PharmD

Office: (210) 617-5300 ext 15969

Email: kimberlyk.Summers@va.gov