preparing the irb and investigators for an external audit/site visit

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Preparing the IRB and Investigators for an External Audit/Site Visit Cynthia Monahan, MBA, CIP IRB Director Boston University Charles River Campus IRB

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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 - PowerPoint PPT Presentation

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Page 1: 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

Page 2: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 3: Preparing the IRB and Investigators for an External Audit/Site 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

Page 4: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 5: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 6: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 7: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 8: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 9: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 10: Preparing the IRB and Investigators for an External Audit/Site 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

Page 11: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 12: Preparing the IRB and Investigators for an External Audit/Site 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

Page 13: Preparing the IRB and Investigators for an External Audit/Site Visit

Evaluation Outcomes

OHRP does not identify any areas of non-compliance

OHRP recommends improvements Institution is free to implement the

recommendations or not

Page 14: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 15: Preparing the IRB and Investigators for an External Audit/Site Visit

FDA Inspections

Page 16: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 17: Preparing the IRB and Investigators for an External Audit/Site Visit

FDA Inspections

Routine Inspections Every 5 years

Directed Inspections FDA receives information that calls an IRB’s

practices into question

Page 18: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 19: Preparing the IRB and Investigators for an External Audit/Site Visit

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!!

Page 20: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 21: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 22: Preparing the IRB and Investigators for an External Audit/Site Visit

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)

Page 23: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 24: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 25: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 26: Preparing the IRB and Investigators for an External Audit/Site Visit

2013 BIMO Metrics

IRB Inspections: 174Clinical Investigator Investigations:

664

Page 27: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 28: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 29: Preparing the IRB and Investigators for an External Audit/Site Visit

Association for the Accreditation for Human Research Protection

Programs (AAHRPP)

Page 30: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 31: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 32: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 33: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 34: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 35: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 36: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 37: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 38: Preparing the IRB and Investigators for an External Audit/Site Visit

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.)

Page 39: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 40: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 41: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 42: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 43: Preparing the IRB and Investigators for an External Audit/Site Visit

Council Review

Council on Accreditation makes the decision about accreditation

Accreditation Status New Applicants

Full Accreditation Qualified Accreditation Accreditation Pending Accreditation Withheld

Page 44: Preparing the IRB and Investigators for an External Audit/Site Visit

Preparing and Navigating for the Inspection/Visit

Page 45: Preparing the IRB and Investigators for an External Audit/Site 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

Page 46: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 47: Preparing the IRB and Investigators for an External Audit/Site Visit

During the Inspection/Visit

The Institutional representatives should meet the inspector/visitor

Arrive on time Ask for identification

Page 48: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 49: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 50: Preparing the IRB and Investigators for an External Audit/Site Visit

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

Page 51: Preparing the IRB and Investigators for an External Audit/Site Visit

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/