Preparing the IRB and Investigators for an External Audit/Site Visit
description
Transcript of Preparing the IRB and Investigators for an External Audit/Site Visit
Preparing the IRB and Investigators for an
External Audit/Site Visit
Cynthia Monahan, MBA, CIP
IRB Director
Boston University Charles River Campus IRB
Table of Contents
Office for Human Research Protections (OHRP) Compliance Oversight Evaluations
Food and Drug Administration (FDA) Inspections
Association for the Accreditation of Human Research Protection Programs (AAHRPP) Site Visit
Preparing and Navigating the Inspection/Visit
OHRP Compliance Oversight Evaluation
Division of Compliance Oversight (DCO) evaluates, at OHRP’s discretion, written substantive indications of noncompliance with HHS regulations
DCO also conducts a program of not-for-cause surveillance evaluations of institutions, and receives, reviews, and responds to incident reports from Assured institutions
OHRP Not-for-cause Evaluation
Visit is not initiated by a complaint or report of possible non-compliance
Institutions are selected based on: Volume History of low level of reporting to OHRP Need to evaluate that corrective actions from a previous
for-cause evaluation have been implemented Geographic location Accreditation status Results of recent evaluations/audits by other regulatory
agencies
OHRP Not-for-cause Evaluation
OHRP notifies Institutional Officials in writing of evaluation
Notice will include whether interviews will be conducted and if an on-site visit will be conducted Institutional officials, IRB members, and investigators
OHRP requests the following information by a specified date: Policies and procedures Recent meeting minutes List of active IRB protocols
OHRP For-Cause Evaluation
Evaluation is in response to an allegation of non-compliance
Sources of non-compliance include: research subjects, investigators, research staff, and Institutional Officials
OHRP For-Cause Evaluation
OHRP notifies institutional officials in writing of evaluation
Initial letter includes: Description of the allegation Request for the institution to conduct an investigation Request for written response by a specified date Corrective action plan if investigation reveals any non-
compliance Explanation of OHRP evaluation procedures
OHRP On-Site Visit
In most cases, on-site visits are not required; however, visit will be required if concerns cannot be resolved through correspondence
Majority of on-site visits are for-cause Most on-site visits are announced 1-2 weeks
in advance; however, there is no requirement that visit must be announced
OHRP On-Site Visit
Visits are conducted by a team of 2-5 OHRP professionals and 2-5 external consultants
Visits are usually announced by telephone and in writing
OHRP is informing the institution that the visit will occur NOT inquiring about scheduling an appointment
OHRP provides agenda for visit
OHRP On-Site Visit
OHRP will request list of human subjects research
3-5 days in advance of visit, OHRP will identify 50-100 specific protocols and request that they be available for review; medical records may also be requested
Minutes from the past 3 years will be reviewed
Visit usually lasts 3-5 days
OHRP On-Site Visit
Visit begins with an introductory meeting with the institutional officials and other appropriate officials
1 hour/day devoted to on-site review of the IRB
1 day devoted to meetings with IRB chairs, IRB members, administrators, investigators, and research staff
Exit interview at the end of the visit
OHRP On-Site Visit
Exit interview: Determinations and required corrective actions
are presented If immediate action is required, determination
letter may be issued at exit interview OHRP determination letters are publicly available
and are posted on the OHRP website
Evaluation Outcomes
OHRP does not identify any areas of non-compliance
OHRP recommends improvements Institution is free to implement the
recommendations or not
Evaluation Outcomes (cont’d)
OHRP determines that there is non-compliance Institution is required to develop and implement
corrective actions Restricts or attaches conditions to its approval of the
institutions FWA Suspends its approval of the institutions FWA Temporarily suspend or permanently remove an
institution or investigator from specific projects Notify scientific peer groups of non-compliance Institution and/or investigator is debarred Refer the matter to another Federal agency
FDA Inspections
Bioresearch Monitoring (BIMO) Program
FDA developed BIMO to ensure: The protection of the rights, safety, and welfare of
human research subjects The quality and integrity of data submitted to the
Agency BIMO Program involves site visits to clinical
investigators, sponsors, monitors, contract research organizations, IRBs, nonclinical (animal) laboratories, and bioequivalence analytical laboratories
FDA Inspections
Routine Inspections Every 5 years
Directed Inspections FDA receives information that calls an IRB’s
practices into question
FDA Inspections
FDA inspector will contact the institution with the notification of intent to inspect
FDA inspector is not calling to schedule an appointment; this is a notification that you will be inspected
FDA Inspections
The PI or his/her representatives should meet the inspector and receive and sign the FDA form 482 “Notice of Inspection.”
Request to see the inspector’s identification if he/she does not present it to you
Write down the inspector’s identification information—you cannot make a copy of the inspector’s badge!!
FDA Inspections
What does the FDA inspect? IRB written procedures IRB membership IRB meeting minutes Consent forms Correspondence between the IRB and PI Correspondence regarding unanticipated problems
and serious and/or continuing non-compliance
FDA Inspections
What does the FDA inspect (cont’d) Non-significant risk (NSR)/Significant Risk (SR)
device determinations Study files Documentation of approvals and waivers Humanitarian use Devices (HUD) Pediatric findings
After the FDA Inspection
The FDA inspector will hold an exit interview at the conclusion of the audit to discuss findings and deficiencies
Document the interview, specifically noting observations, comments, and commitments
Any deficiencies will be noted on the FDA form 483 and given to the PI
IRB should respond to the 483 in writing (within 15 days)
After the FDA Inspection
After the inspection, the inspector will write an Establishment Inspection Report (EIR) and submit it to FDA headquarters
After the report has been evaluated you will receive one of three letters: No action indicated (NAI): No objectionable
conditions or practices were found during the inspection, or the significance of the objectionable conditions does not justify further FDA action
After the FDA Inspection
Post-inspection letters (cont’d)Voluntary Action Indicated (VAI): Objectionable conditions were found and documented, but the FDA is not prepared to take or recommend further regulatory action because the objectionable conditions are few and do not seriously impact subject safety or data integrityOfficial Action Indicated (OAI): Regulatory violations uncovered during the inspection are repeated or deliberate and/or involve submission of false information to FDA or to the sponsor
FDA Actions for Non-Compliance
Administrative Actions Re-inspect to verify corrective actions Withhold approval of new studies No new subjects can be enrolled into ongoing studies Terminate ongoing studies
Disqualification
2013 BIMO Metrics
IRB Inspections: 174Clinical Investigator Investigations:
664
Most Common IRB Deficiencies
Inadequate initial and/or continuing review Inadequate SOPs Inadequate membership rosters Inadequate meeting minutes Quorum issues Subpart D issues Inadequate communication with CI/institution Lack of or incorrect SR/NSR determination
Most Common Clinical Investigator Deficiencies
Failure to follow the investigational plan and/or regulations
Protocol deviations Inadequate recordkeeping Inadequate accountability for the
investigational product Inadequate communication with the IRB Inadequate subject protection-- failure to report
AEs and informed consent issues
Association for the Accreditation for Human Research Protection
Programs (AAHRPP)
Who is AAHRPP?
Independent non-profit accrediting body Voluntary, peer-driven, educational model
Site Visitors Council Members
Ensures that HRPP meet rigorous standards for quality and protection
Tangible evidence of commitment to ethical research and continuous improvement Policies, procedures, and practices
Provides assurance that HRPP is focused on excellence Research subjects, researchers, sponsors, federal regulators
Why AAHRPP Accreditation?
Earn respect and meet expectations of peers Over 60% of US research-intensive universities and over 65% of
US medical schools have or are in the process of AAHRPP Accreditation
Leadership role in collaborative efforts External IRB reviews
Competitive edge with sponsors/funders Reduce the risk of non-compliance
Streamlined policies
Enhance standing with US federal agencies Benefit from a common commitment to continuous quality
improvement
Goals, Principles, and Standards
AAHRPP has adopted nine overarching principles for protecting human research participants, which serve as the foundation for the AAHRPP Accreditation Standards for Human Research Protection Programs.
The AAHRPP Accreditation Standards themselves describe what Organizations can do to consistently act on these principles by applying them to the diverse organizational and cultural contexts in which research is conducted and reviewed
AAHRPP Accreditation Standards
Domain I: Organization Structural characteristics of the Organization
Domain II: Institutional Review Board/Ethics Committee Review and oversight of research Ensure independence of ethics review
Domain III: Researcher and Research Staff Requirements for researchers and research staff involved
in human subjects research
http://www.aahrpp.org/apply/process-overview/standards
Accreditation Process
Application preparation (Step 1) Submit Application to AAHRPP for review
On-site evaluation (Step 2) Site visitors conduct on-site visit
Council Review Council reviews the Application, Draft Site Visit Report, and
response and determines accreditation status
Notification of accreditation status Report sent to Organization detailing the status of the
accreditation
Preparing for Accreditation
Conduct a self-assessment Allows the Organization to review its HRPP and evaluate
its compliance with the AAHRPP Accreditation Standards Create list of supporting documents (forms, policies,
checklists, etc.) and make copies (this becomes part of your Application)
Draft an element-by-element index to the supporting documents (this becomes part of your Application)
Use Evaluation Instrument for Accreditation Provides direction on the meaning of each Standard and
Element
Application Steps
Step 1 (Application Review) Submit Application including: 1) program overview, 2)
copies of supporting documents (policies/procedures, checklists, forms, etc.), and 3) an index for the supporting documents
AAHRPP will review Application and provide feedback within 45 days
Address any issues with feedback
Application Steps (cont’d)
Step 2 (Site Visit) Once all issues have been resolved, AAHRPP
will schedule the site visit Site visits are typically scheduled within 3
months after Application is considered to be complete
On-site Visit
Depending on size of the Organization, the visit will last 2-4 days
Four-Eight Weeks Before the Visit, AAHRPP will send the following: Draft agenda List of people to be interviewed Explanation of the types of visits List of the AAHRPP site visitors Request for logistical and travel information Request to set aside rooms to be used by site visitors Request for additional info (e.g. electronic system, etc.)
On-site Visit
One week before the Visit, AAHRPP will send the following: Final agenda Logistical details List of records and documents that must be ready
Protocol files Average is 20-30 files
On-Site Visit
During the Visit: Introduction Session
AAHRPP site visitors, lead contact from Organization, Organizational Official, other staff members
AAHRPP site team leader will describe the accreditation process
Program Overview Opportunity for site visitors to ask questions Organization provides overview of Program
File Review Site visitors will review requested files
On-Site Visit
During the Visit (cont’d) Interviews
Confidential and limited to individuals on the agenda Closeout Session
Site team leader will provide high-level overview and specific observations about each Standard
Organization is provided with the comments that will be in the report
Site visitors may provide suggestions but they will not be included in the report
Organization attendees usually the same as Introduction session
After the Visit
AAHRPP will provide a Draft Site Visit Report to Organization within 30 days of the site visit
Organization must respond within 30 days Once response has been completed and
accepted, it is sent to Council for review
Council Review
Council on Accreditation makes the decision about accreditation
Accreditation Status New Applicants
Full Accreditation Qualified Accreditation Accreditation Pending Accreditation Withheld
Preparing and Navigating for the Inspection/Visit
Preparing for the Inspection/Visit
Ensure that all study documentation is available for review for the inspector/visitor
Review study documentation for: Comprehensiveness, accuracy, and compliance Weakness/gaps; correct those that can be
corrected (i.e. file violations, notes-to-file, locate missing documents, etc.)
Unresolved or outstanding issues Organize documents
Preparing for the Inspection/Visit
Notify all appropriate officials/individuals Prepare work space for the inspector/visitor Access to copy machine Access to electronic systems
Involve IT Department Issue Temporary passwords Training session
During the Inspection/Visit
The Institutional representatives should meet the inspector/visitor
Arrive on time Ask for identification
During the Inspection/Visit
If the inspector/visitor requests copies of documents: Remove subject identifiers from the copies given to
the inspector/visitor Make a copy for yourself The inspector’s/visitor’s copies should be stamped
‘Confidential’ and your copies should be stamped ‘Copy.’
Set aside time each day to talk with the inspector/visitor
During the Inspection/Visit
How to answer questions from the inspector/visitor: Be concise; answer only the question that is asked Always be clear with answers to questions Answer honestly and openly DO NOT volunteer information DO NOT guess or speculate DO NOT argue If you don’t know the answer, write down the question
and refer it to the appropriate person Keep a log of questions asked by the inspector
Ongoing Preparation Process
Internal audits Review FDA/OHRP determination letters Adequate IRB Staffing Continuing education for IRB members, IRB
staff, and researchers Maintain and update IRB policies
Resources
BIMO
http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/default.htm
OHRP: Compliance Oversighthttp://www.hhs.gov/ohrp/compliance/index.html
AAHRPPhttp://www.aahrpp.org/