POLICIESAND
STANDARD OPERATING PROCEDURES
FOR THE
DURHAM VETERANS AFFAIRS MEDICAL CENTER
HUMAN RESEARCH PROTECTION PROGRAM
A PUBLICATION OF THE RESEARCH AND DEVELOPMENT SERVICE
DURHAM VAMC
508 Fulton Street
Durham, North Carolina 27705
July 2005
Revised: October 2006, April 2008, September 2008, September 2009, October 2010, March 2011, May 2011, November 2011, January 2013, March 2013, August 2013, and June 2014, March 2015
CURRENT: September 2015
______Durham VAMC IRB SOP: Page 1 of 301
Table of Contents
MISSION STATEMENT
INTRODUCTION
REVISIONS
ABBREVIATIONS
LAY LANGUAGE FOR INFORMED CONSENT
GLOSSARY
STATEMENT OF AUTHORITY AND PURPOSE
Introduction
1.Ethical Principles Governing the IRB
2.Regulatory Mandate to Protect Human Subjects
3. Authority
4. Responsibility
GA 101: POLICIES AND PROCEDURES MAINTENANCE
1. Policy
1.1 Review, Revision, and Approval of Policies & Procedures
1.2 SOP Dissemination and Training
1.3 Forms
2. Scope
3. Responsibility
GA 102: RESEARCH REQUIRED TRAINING, EDUCATION, AND OTHER RESEARCH PERSONNEL DOCUMENTATION
1. Policy
1.1 Training
1.2 Scope of Practice
1.2.1 Scope of Practice Updates/Revisions
1.3 Staff Listing
1.4 Credentialing and Privileging
1.5 Documentation
2. Scope
3. Responsibility
GA 103: MANAGEMENT OF IRB PERSONNEL
1. Policy
1.1 Job Descriptions and Performance Evaluations
1.2 Staff Positions
1.3 Hiring and Terminating IRB Staff
1.4 Delegation of Authority or Responsibility
1.5 Documentation
2. Scope
3. Responsibility
GA 104: CONFLICT OF INTEREST
1. Policy
1.1 Definition of a COI
1.2 Disclosure and Documentation of Financial Interest and COI
1.3 Employees
1.4 Education and Training in COI
1.5 Review of COI Forms
1.6 Organizational Conflict of Interest
1.7 Undue Influence of IRB Members and Staff
1.8 Failure to Disclose a COI
2. Scope
3. Responsibility
GA 105: SIGNATORY AUTHORITY
1. Policy
1.1 Authorization for Signatory Authority
1.2 Results of Reviews, Actions and Decisions
1.3 Routine Internal Correspondence
1.4 Routine Correspondence with the IRB
1.5 Correspondence with External Agencies
1.6 Decisions Made by Chairperson
2. Scope
3. Responsibility
OR 201: COMPOSITION OF THE IRB
1. Policy
1.1 Membership Selection Criteria
1.2 Composition of the Board
2. Scope
3. Responsibility
OR 202: MANAGEMENT OF THE IRB
1. Policy
1.1 Term
1.2 Appointments
1.3 Evaluations
1.4 Resignations and Removals
1.5 Compensation
1.6 Liability Insurance
2. Scope
3. Responsibility
OR 203: DUTIES OF IRB MEMBERS
1. Policy
1.1 Duty to the Durham VAMC
1.2 Term of Duty
1.3 Specific Duties
1.3.1 Regular Members
1.3.2 Primary Reviewers
1.3.3 Ex-Officio Members
2. Scope
3. Responsibility
FO 301: RESEARCH SUBMISSION REQUIREMENTS
1. Policy
1.1 Submission Requirements for Initial Review
1.2 Submission Requirements for Continuing Review
1.2.1 Changes in Study Status
1.2.2 Progress Report and/or Request to Renew IRB Approval
1.3 Action Taken If Documentation is Not Adequate or Additional Information is Required
2. Scope
3. Responsibility
FO 302: RESEARCH EXEMPT FROM IRB REVIEW
1. Policy
1.1 Exempt Research Activities (non-FDA regulated)
1.2 Exempt Research Activities (FDA-regulated)
1.3 Granting Exemptions
1.4 Documentation of Exempt Status
1.5 Determination of Human Subject Research
2. Scope
3. Responsibility
FO 303: IRB MEETING ADMINISTRATION
1. POLICY
1.1 Quorum
1.2 Primary Reviewers
1.3 Meeting Materials Sent Prior to IRB Meetings
1.3.1 Agenda
1.3.2 Reviewer materials
1.4 Minutes
1.5 Telephone/Video Use
1.5.1 Convened meeting using Telephone Conference (speakerphone)
1.5.2 Meetings Conducted Via Video Conference Calls
1.6 Voting
2. Scope
3. Responsibility
FO 304: ADMINISTRATIVE REVIEW AND DISTRIBUTION OF MATERIALS
1. Policy
1.1 Exemptions
1.2 Incomplete Submissions
1.3 Scheduling for Review
1.4 Distribution to Members Prior to IRB Meetings
1.5 Confidentiality
2. Scope
3. Responsibility
FO305: DOCUMENTATION AND DOCUMENT MANAGEMENT
1. Policy
1.1 Investigator Notifications
1.1.1 Initial Submission
1.1.2 Renewals and Revisions
1.1.3 Notification of Final Approval
1.1.4 Disapproval
1.2 Document Retention
1.2.1 Study-Related Documents
1.3 IRB Administration Documents
1.4 Destruction of Copies
1.5 Archiving and Destruction
2. Scope
3. Responsibility
RR 401: EXPEDITED REVIEW
1. Policy
1.1 Expedited Review Criteria
1.2 Expedited Review Eligibility
1.3 Expedited Review for Continuing Review
1.4 Expedited Review Procedures
1.5 Notification of the IRB
1.6 Documentation
1.7 Additional Items That May be Reviewed by the Chairperson or Designee
1.7.1 Conditional approval pending minor modifications/revisions
1.7.2 On-going Continuing review
1.7.3 Audit Reports
1.7.4 Translations
2. Scope
3. Responsibility
RR 402: INITIAL REVIEW: CRITERIA FOR IRB APPROVAL
1. Policy
1.1 Minimal Criteria for Approval of Research
1.2 Participation of Non-Veterans in Research
1.3 Other Criteria
2. Scope
3. Responsibility
RR 403: CONTINUING REVIEW: ONGOING
1. Policy
1.1 Investigator Compliance Reviews
1.2 Third Party Verification
1.3 Reportable Events to the IRB
1.3.1 Definitions
1.3.2 List of problems that require reporting
1.4. Rapidly Reportable Events
1.4.1 Serious Unanticipated Problems Involving Risks to Subjects or Others
1.4.2 Local Unanticipated SAEs
1.4.3 Apparent Serious or Continuing Noncompliance
1.5 IRB Review of Serious Unanticipated Problems and Unanticipated SAEs
1.6 IRB Review of Apparent Serious or Continuing Noncompliance
1.6.1 Reporting Noncompliance
1.7 Amendments/Modifications
1.8 Significant New Findings
1.9 Reports from Employees, Staff and Faculty
1.9.1 Allegation of Noncompliance
1.9.2 Research Misconduct
1.10 Complaints and Inquiries of the HRPP
1.11 Suspensions and Terminations of IRB Approval
1.11.1 Reporting Suspensions and Terminations
1.12 Administrative Hold
1.13 Unapproved Research
1.14 Research Information Protection Incidents
1.14.1 Immediate Reporting
1.14.2 Regular Reporting
1.14.3 Reports to Central Office and Regional ORO Office
2. Scope
3. Responsibility
RR 404: CONTINUING REVIEW: CRITERIA FOR RENEWAL
1. Policy
1.1 Interval for Review for Purposes of Renewal
1.2 Extensions of Approval Period
1.3 Criteria for Renewal
1.4 IRB Review
1.5 Possible Outcomes of Continuing Review
1.6 Expiration of IRB approval
1.7 Expedited Review for Renewal
1.8 IRB Documentation of Continuing Review
2. Scope
3. Responsibility
RR 405: STUDY COMPLETION
1. Policy
1.1 Determining When a Project Can be Closed
1.2 Completion Reports
2. Scope
3. Responsibility
RR 406: CATEGORIES OF ACTION
1. Policy
1.1 Determinations
1.2 Investigator Appeal of IRB Action
2. Scope
3. Responsibility
RR 407: PRIVACY OFFICER & INFORMATION SECURITY OFFICER REVIEWS
1. Policy
1.1 Responsibilities
2. Scope
3. Responsibility
SC 501: VULERNABLE POPULATIONS
1. Policy
1.1 Documentation of Vulnerability
1.2 Populations Considered to be Categorically Vulnerable
1.3 Populations in Which Research is Not Allowed
1.3.1 Fetuses
1.3.2 Neonates
1.3.3 In Vitro Fertilization
1.3.4 Prisoners of War
1.4 Prisoners
1.4.1 When Subjects Become Prisoners During a Research Protocol
1.5 Children
1.5.1 Requirements
1.5.2 Application
1.6 Pregnant Women
1.7 Subjects Who Lack Decision-making Capacity
1.7.1 Determination of Capacity
1.7.2 Temporary or Fluctuating Lack of Decision-Making Capacity
1.7.3 Criteria for Enrollment
1.7.4 IRB Determination
1.7.5 Additional Safeguards
1.8 Other Vulnerable Groups
1.9 Subjects in "Treatment IND” studies
2. Scope
3. Responsibility
SC 502: CATEGORIES OF RESEARCH
1.1 Clinical Research Involving Investigational Drugs
1.1.1 IND Exemptions
1.1.2 Research Service Responsibilities
1.1.3 Pharmacy Service/ Investigational Pharmacist Responsibilities
1.2 Clinical Research Involving Devices
1.3 Humanitarian Use Device
1.4 Genetic Research
1.4.1 Subjects of Genetic Research
1.5 Prospective Research in Emergency Settings (21 CFR 50.24)
1.6 Emergency Use of Test Articles
1.6.1 Use of data generated prior to IRB approval
1.7 Medical Records and Chart Review
1.8 Residual Body Fluids, Tissues and Recognizable Body Parts
1.9 Collaborative Research
1.9.1 IRB of Record Approval
1.9.2 Research Data
1.9.3 Written Agreements
1.10 Certificates of Confidentiality
2. Scope
3. Responsibility
SC 503: ENGAGEMENT IN RESEARCH
1. Policy
1.1 Engagement
1.2 Non-Engagement
2. Scope
3. Responsibility
SC 504: MULTI-SITE STUDIES
1. Policy
1.1 Investigator Responsibilities
1.1.1 Lead Investigator of a VA Multi-Site Study
1.1.2 Local Site Investigator (LSI) for a Multi-Site Study
1.1.3 Durham VAMC Researchers Conducting Research at Remote Sites
1.2 Durham VAMC Responsibilities for Multi-Site Research When the Durham’s Investigator is the Multi-Site Study PI for All Participating Facilities and the VA Central IRB is Not Being Used
1.3 VA Central Institutional Review Board (CIRB) Studies
1.3.1 CIRB Submission Procedures
1.3.2 Durham Local Site Investigator (LSI) Responsibilities
1.3.3 Durham VAMC Responsibilities
1.3.4 CIRB Responsibilities
2. Scope
3. Responsibility
SC 505: INTERNATIONAL RESEARCH
1. Policy
1.1 Multi-Site Trials
1.2 IRB and Facility Director Permission
1.3 FWA and Approval
1.4 Department of Defense (DoD) International Research Requirements
2. Scope
3. Responsibility
SC 506: VA DATABASE AND RESEARCH ACCESS FORM REQUESTS FOR RESEARCH PROTOCOLS
1 Policy
2 Scope
2.1 Completion of Form 9957
2.2 Routing of Form 9957
3 Responsibility
3.1 Requestor (Customer)
3.2 General Medical Research Office
SC 507: RESEARCH DATA REPOSITORIES
1 Policy
2 Scope
2.1 Definitions
2.2. Data
2.2.1 Sources of Data
2.2.2 Data Collection
2.2.3 Data Distribution
2.3 Establishing and Administering a Research Data Repository
2.3.1 Administration and Oversight
2.3.2 Records
2.3.3 Standard Operating Procedures
2.3.4 Reporting Requirements
2.3.5 Conflict of interest (COI)
2.3.6 Destruction of Data
2.3.7 Termination
2.4 Using Data From a Research Data Repository
2.5 Preparatory to Research
3 Responsibility
3.1 Institutional Review Board (IRB)
3.2 Research and Development Committee (R&DC)
3.3 Associate Chief of Staff for Research & Development (ACOS/R&D)
3.4 Research Repository Administrator
3.5 Investigator
CO 601: REPORTING TO OTHER ENTITIES
1. Policy
1.1 Communications to Others
1.1.1 Reports to ORO Regional Office (RO)
1.1.2 Reports to ORO Central Office (CO)
1.1.3 Reports to OHRP
1.2 Other Reportable Events
2. Scope
3. Responsibility
CO 602: RESEARCH PERSONNEL DRUG SAFETY ALERTS & NOTIFICATION
1. Policy
2. Scope
3.Responsibilities
IC 701: GENERAL REQUIREMENTS AND DOCUMENTATION OF INFORMED CONSENT
1. Policy
1.1 General Requirements for Informed Consent
1.2 Required Elements of Informed Consent
1.3 Additional Elements of Informed Consent
1.3.1 Common Rule Requirements
1.3.2 VA Requirements
1.3.3 Other Requirements
1.3.4 ClinicalTrials.gov Requirements
1.4 Consent for Photographs, Voice, or Video Recordings for Research Purposes
1.5 Documentation of Informed Consent
1.6 Cognitively Impaired Subjects
1.7 Waiver of Documentation
1.8 Use of Facsimile or Mail to Document Informed Consent
2. Scope
3. Responsibility
IC 702: WAIVER OF INFORMED CONSENT
1. Policy
1.1 IRB Waives One or More Requirements of Informed Consent
1.2 The IRB Waives the Requirement to Obtain Documentation of Consent
1.3 An Emergency Situation Prior to IRB Review and Approval
2. Scope
3. Responsibility
IC 703: SURROGATE CONSENT AND ASSENT
1. Policy
1.1 Assessment of Capacity
1.2 Investigators’ Responsibilities for Surrogate Consent
1.3 Legally Authorized Representatives (LARs)
1.3.1 Authorized Person
1.3.2 Responsibilities of LARs
1.4 Dissent or Assent
1.4.1Use of Assent
1.5 Fluctuating Capacity
2. Scope
3. Responsibility
IC 704: PRIVACY RULE AND RESEARCH
1. Policy
1.1 Authorization
1.2 Waiver of Authorization
1.2.1 IRB Documentation
1.3 Limited Data Set
1.4 Decedent Research
1.5 Preparatory to Research
1.6 Revocation of Authorization
2. Scope
3. Responsibility
RI 801: INVESTIGATOR RESPONSIBILITIES
1. Policy
1.1 Investigator Responsibilities
1.2 Advertisements
1.3 Investigational Drugs
1.4 Investigational Devices
1.5 Student/Trainee-Conducted Research
1.6 Tissue Banking
2. Scope
3. Responsibility
RI 802: RESEARCH PROTOCOL
1. Policy
1.1 Investigator Responsibility for Drafting a Research Protocol
2. Scope
3. Responsibility
RI 803: RESEARCH RECORDS AND DOCUMENTATION OF RESEARCH
1. Policy
1.1 VHA Health Record
1.2 Research Consent Notes
1.3 Research-Study Participant Notes (Clinical Warnings)
1.3.1 Entering Research-Study Participant Notes (Clinical Warnings)
1.3.2 Removing Research-Study Participant Notes (Clinical Warnings)
1.4 Progress Notes
1.5 Research Consults
1.6 Research Records
2. Scope
3. Responsibility
QA 901: QUALITY ASSURANCE/CONTINUOUS QUALITY IMPROVEMENT PROGRAM
1. Policy
1.1 Evaluation of the HRPP
2. Scope
3. Responsibility
QA 902: AUDITS BY REGULATORY AGENCIES
1. Policy
1.1 Preparing for an Audit
1.2 Participating in an Audit
1.3 Follow-up After an Audit
2. Scope
3. Responsibility
QA 903: STUDY SITE MONITORING VISITS
1. Policy
1.1Preparing for a Monitoring Visit
1.2Monitor Access to Pertinent Medical Records of VA Study Subjects
1.2.1 Limited Read-Only Access to Selected Data
1.2.2 VA Employee Driver
1.3Participating in a Monitoring Visit
1.4Follow-up After a Monitoring Visit
2. Scope
3. Responsibility
QA 904: RESEARCH PARTICIPANT OUTREACH PROGRAM
1. Policy
1.1 Outreach Activities
1.1.1 Study Team Personnel
1.1.2IRB and/or Research and Development Personnel
2. Scope
3. Responsibilities
QA 905: HUMAN SUBJECT RESEACH AUDITING PROGRAM
1. Policy
1.1 Audit Program
1.2 IRB Review of Audit Reports
1.3 Reporting Audit Findings to Oversight Authorities
2. Scope
3. Responsibilities
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Mission Statement
MISSION STATEMENT
The overarching mission of the Human Research Protection Program (HRPP) at the Durham VA Medical Center is to protect the rights and welfare of human research participants recruited to participate in research conducted under the auspices of the Durham VAMC. Rather than ensuring mere compliance with the federal regulations, the Durham VA HRPP strives to adhere to the highest ethical standards in its protection of human research participants and seeks to further develop the methods and mechanisms for protecting human research participants. In service of this mission, the HRPP endeavors to:
- Create an atmosphere of respect for, and awareness of, the rights and welfare of human research participants at the Durham VAMC.
- Continue to inform established researchers about the application of the federal regulations and ethical principles to their particular area of research in an effort to keep researchers current with evolving standards.
- Educate students, faculty, and staff who conduct research about the ethical principles and federal regulations guiding research with humans.
- Assess the effectiveness of the Institutional Review Board (IRB) in its review of research activities, facilitation of compliance of researchers with the federal regulations, and protection of research participants.
- Develop new approaches that better serve the overarching mission of the HRPP, such as state-of-the-art educational materials, more efficient methods for processing applications, tracking and monitoring research activities, and assessing the overall effectiveness of the HRPP.
______Durham VAMC IRB SOP: Page 1 of 301
Revisions
INTRODUCTION
Regulations require that Institutional Review Boards (IRBs) have written policies and procedures, and that activities at the institution are carried out as described in the written policies and procedures document. These Standard Operating Policies and Procedures (SOP) are written to enable the Durham VAMC IRB to maintain a system of compliance. The SOPs of an IRB reflect not only the laws and regulations, but also the underlying ethical principles that are the basis of the IRB's mandate. Finally, these policies also reflect the overarching commitment of the Durham VAMC’s Human Research Protections Program (HRPP) to provide protection for all human subjects involved in research conducted under the direction of its students, staff and faculty.
The ethically responsible researcher is expected to carry the dual burden to advance knowledge that can improve the human condition or generate new knowledge and, at the same time, to recognize the absolute imperative to treat human research subjects with the utmost care and respect.
It is not unreasonable to ask others to share this burden, indeed, the institutions, sponsors, and society as a whole who expect to benefit from this research should be expected to share in the responsibility of conducting ethical research.
This burden also falls, then, to the men and women who sit on Institutional Review Boards. They are, certainly, expected to act as gatekeepers, to apply proper oversight of the research enterprise in its drive to find the newest therapy and to advance knowledge of the basics of biological and behavioral mechanisms, and they are expected to share the responsibility of protecting the human subjects of this research.
These SOPs apply to all the day-to-day operations of theIRB. The SOPs apply to all members of the IRB, all members who serve on it as part of their overall institutional responsibilities, and all others who must subscribe to its decisions and its requirements (for example, the clinical Investigators, research managers/coordinators, research nurses, support staff, etc.). Inspection of a Human Research Protections Program (HRPP) by the FDA,the accrediting organization under contract with VA , Office for Human Research Protections (OHRP) and the Office for Research Oversight (ORO) inspection of an IRB always includes an assessment of the IRB’s SOP.
These SOPs will be reviewed every two years or as necessary to ensure that they are up-to-date, that new legislation or regulations are reflected in the policies and that daily activities are being performed as described in the SOPs.
These policies are based on current regulations, ethical principles, and guidelines for the protection of the human subjects of biomedical and behavioral research. As guidelines and regulations change in response to new technologies, new interpretation of principles, and other emerging issues, it is recognized that policies and procedures are evolving through the practice of human research protection. These evolving policies
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Abbreviations
ABBREVIATIONS
ACOS/R&DAssociate Chief of Staff for Research & Development
ADEAdverse Drug Event/Experience
AEAdverse Event
AO/RAdministrative Officer for Research
CDCCenters for Disease Control and Prevention
CFRCode of Federal Regulations
CGMPCurrent Good Manufacturing Practice
CIOMSCouncil for International Organizations of Medical Science
CLIAClinical Laboratory Improvement Act
CPRSComputerized Patient Record System
CRAClinical Research Associate
CRADOChief Research and Development Officer
CRCClinical Research Coordinator
CRFCase Report Form
CROContract Research Organizations
CSPCooperative Studies Program (VA)
CSPCCCooperative Studies Program Coordinating Center (VA)
CRPCCClinical Research Pharmacy Coordinating Center (VA)
DHHSDepartment of Health and Human Services (or HHS)
DoDDepartment of Defense
DPAHCDurable Power of Attorney for Health Care
DSMBData Safety and Monitoring Board
FDAFood and Drug Administration
GCPGood Clinical Practice
GLPGood Laboratory Practice
GMPGood Manufacturing Practice
HRPPHuman Research Protections Program
IBCInstitutional Biosafety Committee
ICFInformed Consent Form
ICHInternational Conference on Harmonisation
IDEInvestigational Device Exemption
IDMCIndependent Data Monitoring Committee
IMRInstitute for Medical Research
IECIndependent Ethics Committee
INDInvestigational New Drug
IOInstitutional Official
IRBInstitutional Review Board
IVDIn Vitro Diagnostic
LARLegally Authorized Representative
MCDMedical Center Director
NDANew Drug Application
NIHNational Institutes of Health
OHRPOffice for Human Research Protections (former OPRR)
OPRROffice for Protection from Research Risks
ORDOffice of Research and Development
OROOffice of Research Oversight
PIPrincipal Investigator
PHSPublic Health Service
PMAPremarket Approval (Application)
QAQuality Assurance
QCQuality Control
RACRecombinant DNA Advisory Committee (NIH)
SAESerious Adverse Event
SMARTSite Monitoring and Review Team (VA)
SOPStandard Operating Procedure
UAEUnexpected Adverse Event
WOCWithout Compensation
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Lay Language for Informed Consent
LAY LANGUAGE FOR INFORMED CONSENT
Term / Definitionacute / new, recent, sudden
adverse effect / side effect
assay / lab test
benign / not malignant, usually without serious consequences
bolus / an amount given all at once
carcinogenic / capable of causing cancer
catheter / a tube for withdrawing or introducing fluids
chronic / continuing for a long time
clinical trial / an experiment with patients
controlled trial / a study in which the experimental procedures are compared to standard (accepted treatments or procedures
culture / test for infection, or organisms that could cause infection
double blind / study in which neither the Investigators nor the subjects know which intervention the subject is receiving
dysplasia / abnormal cells
edema / increased fluid
efficacy / effectiveness
extravasate / to leak outside of a blood vessel
hematoma / a bruise, a black and blue mark
heparin lock / needle placed in the arm with blood thinner to keep the blood from clotting
monitor / check on, keep track of, watch carefully
morbidity / undesired result or complication
mortality / death or death rate
necrosis / death of tissue
oncology / the study of tumors or cancer
percutaneous / through the skin
placebo / a substance of no medical values, an inactive substance
PRN / as needed
protocol / plan of study
random / by chance, like the flip of a coin
relapse / the return of a disease
retrospective / looking back over past experience
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Glossary