Office of Regulatory Affairs & Compliance What to Expect ...research.uthscsa.edu/irb/ORAC Compliance...
Transcript of Office of Regulatory Affairs & Compliance What to Expect ...research.uthscsa.edu/irb/ORAC Compliance...
Office of Regulatory Affairs
& Compliance
What to Expect During a
Compliance Review
Frank EstalaResearch Compliance Manager
Clara VorpahlSenior Research Compliance Specialist
Office of Regulatory
Affairs & Compliance
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• Conducts compliance reviews in medical billing and research
• Oversees the Compliance Hotline
• Privacy Officer/HIPAA
• Report to the President’s Office
An Active Monitoring & Auditing Program is
Important For…
• Maintaining participant and staff safety
• Protecting the Institution and the Researchers
• Maintaining data quality
• Protecting funding
• Measuring compliance with regulatory requirements
• Educate
• Process Improvement
OCR Documentation
Standards
Section Document Requirement/Purpose
File
Location
Reference
(GCP and
Local)
Sponsor
Investigator IND/IDE
FDA
Regulated
Non-FDA
Regulated
Non-
Exempt
Human
Research Exempt
ED-1 Protocol
To document investigator and sponsor agreement to the
protocol, amendments and CRFs; and, to document revisions
of trial-related documents that take effect during trial:
• Initial version that the site was registered
• Amendments and Letters of Amendment
• Subsequent versions
• Investigator signature page
Regulatory
binder
• 21CFR312/812
• ICH Guidance:
E6 GCP,
Sections 1.44,
1.45, 4.5, 5.23,
6, 8.2.2, 8.3.2
X X xForm C or
Protocol
IRB
Exempt
Application
ED-2
Protocol
Training
(Training
Log)
Documentation that trial procedures were reviewed with the
investigator and investigator’s trial staff:
• Summary of start-up calls
• Training meetings (Initiation, Implementation, Investigator
Meeting, Teleconference, List of Training Attendees)
Regulatory
binder
• 21CFR312/812
• ICH Guidance:
E6 GCP,
Sections 4.5,
5.23, 8.2.20
AAHRPP Element:
III.2.A; I.1.D;
UTHSCSA IRB
Investigator’s
Handbook
X X x
ED-3
Delegation
Log/
Signature
Log (IRB B-2
Form)
1. To document the signatures of individuals using initials in
place of a full signature to sign CRFs and source documents.
2. To document the signatures and initials of all persons
authorized to make entries and/or corrections on CRFs.
Include all site staff engaged in research,
such as:
• Clinicians
• Physicians
• Pharmacists
• Data personnel
• Any other individuals authorized to make entries and/or
corrections on CRFs.
3. Key/log must include:
• Initials
• Printed Signature
• Legal Signature, including first and last name
• Credentials (if appropriate)
4. To document Principal Investigator delegation of study-
related task to staff. To outline the roles and responsibilities
delegated by the PI to each team member.
Regulatory
binder
• ICH Guidance:
E6
GCP, Section
8.3.24
AAHRPP
Elements: III.2.A;
III.2.B; VHA Policy
Memo 151-07-07;
VHA Handbook
1200.05 62c;
Handbook of
Operating
Procedures ,
Section 5.8.12
X X X X IRB Form
Internal Compliance
Reviews
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ALL active human research studies are subject to reviews
Why Me?
• Risk-Based*
• At the request of the IRB
• Voluntary
• Triggered by an event or
complaint
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*Risk Variables• Risks to the Subject
• Risks to the Institution
• The tool is divided into 5 sections
– Protocol Risks
– FDA Risks
– Budget/Billing Risk
– IRB Risks
– PI Risks
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Protocol Risks
• Trial Phase
• Sponsor Investigator
• Locally Developed Plan
• IRB Risk
• Recruitment Status
• External Monitoring
• Radiation
• Disclosure Outside Covered Entity
• Sensitive Nature of Study
FDA Risk
• Use of an FDA regulated article
Budget Billing Risk
• Billing Medicare or Private Insurance
• Funding
• Subject Payments
IRB Risks
• Vulnerable Populations
• UPIRSO/AE Reporting
• Deviations
• Waivers of Informed Consent
• Use External IRB
• External Reporting (OHRP, FDA)
PI Risks
• PI Research Experience at
UTHSCSA
• PI History of Noncompliance
• PI workload
Collaborative Review Process• Notification letter to PI with review tool
• Entrance meeting/Survey
• Site Visit (usually 2 business days)
• Summarize findings during site visit
• Email follow-up
• Five days to address issues
• Exit meeting with PI to discuss remaining findings in draft report
• Final report of ORA&C Observations
• PI response to findings (sent to IRB)
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Preparation for Site Visit
ORA&C
• Obtain IRB History
• Review Protocol and Related Docs
• Select Subject Charts for SV
• Location Convenient to PI/Staff
• Work Independently
IRB History
IRB ApprovalsDate of Approval
Approval Type
ICF English Version Approvals
ICF Spanish Version Approvals
Summary of Approval/Amendments Protocol
Investigator Brochure Reconsent
Advertisement Sites
Initial IRB Submission Conditional Approval 29-Jul-14 FB N/A N/A
Initial IRB submission conditional approval. N/A N/A N/A N/A N/A
Initial IRB Submission Final Approval 15-Aug-14 Exp 15-Aug-14 N/A Initial IRB submission final approval.
Dtd 4/23/14
Edition 3.1 Dtd 2/25/14 N/A N/A
UTHSCSA, UHS
Amendment 1 Dtd 9/25/14 1-Oct-14 Exp 1-Oct-14 N/A
Study title updated ZS description to "sodium zirconium cyclosilicate" to be consistent with the US adopted name; increase enrollment from 120 to 200 due to a US FDA request for a less sensitive analysis which necessitated a larger sample size to maintain statistical power; modified the dose stopping rule; removed testing for plasma fasting glucose; administrative changes to correct version and amendment dates. No subjects enrolled to date.
Amendment 1 Dtd 6/27/14 N/A No N/A N/A
Amendment 2 Dtd 10/21/14 27-Oct-14 Exp 27-Oct-14 27-Oct-14
Reduces i-STAT potassium value and provides updates to animal toxicology data; addition of Spanish translated consent form.
Amendment 2 Dtd 10/16/14 N/A No N/A N/A
Amendment 3 Dtd 11/25/14 19-Dec-14 AA N/A 19-Dec-14 Spanish translation. N/A N/A No N/A N/A
PI/Study Team Preparation
• Review OCR Study Doc Standards Policy
• Review ORA&C Tool
• Review Your Records
• Workspace
• Records Readily Available
• Enrollment Logs
• Regulatory Binders (edocs or paper)
• Subject Charts (separate vs together)
• Occasional Check-in
• Schedule Pharmacy Visit
• Promptly Respond to Findings
• Maintain Communication
• Consult with Research Departments
Notification
Entrance Meeting/Survey
Entrance Meeting/Survey
Entrance Meeting/Survey
Site Visit Regulatory Binders
• Sponsor Protocol
• Investigator Brochure
• Form 1572/1571
• Financial Disclosures
• Delegation of Authority Logs
• Initial Protocol/Amendment Training
• Special Procedures Training
• Current CVs & Licenses
• IRB Training/Scopes of Practice
SV Regulatory Binder
Cont.• All IRB Action Letters
– Initial/Contingent Approval
– Amendments
– Progress Reports
– Non-compliance
– UPIRSOs
– Administrative Actions
• Stamped Consent Forms
• Affiliate Approval Letter (UHS, VA)
SV Regulatory Binder Cont.
• Screening/Enrollment Logs
• Investigational Product
Accountability & Temperature Logs
• Labs/Specimens Shipment Records
• Sponsor Safety Reports
• Monitoring Log & Reports
• Case Report Form Templates
• SOP/Manual of Operation
SV Subject Charts
• Signed Consent Form/Reconsents
• Inclusion/Exclusion Checklist
• Laboratory Results
• Test Results (ECG)
• Completed Data Collection Tools
• Medical Records
• Progress Notes
SV Subject Charts Cont.
• Concomitant Medication Logs
• Adverse Event Log
• Deviation Log
• Note to File Explaining
Discrepancies
• Documentation of Payment
What Happens After SV?
• Receive email with issues
• Five business days
• >Five days – issues on draft report
• Coordinate exit meeting
• Post draft report on meeting invite
• Discuss issues during exit meeting
• Receive final signed report via email
• Follow-up with IRB
The Final Report
• PI/Research Coordinator
• IRB (Dr. Kim Summers)
• AVPR (Dr. Joseph Schmelz)
• Affiliate (UHS Research Office, VA
R&D, VA Compliance)
• Department Chair (if warranted)
• Compliance Committee
• UT System
Reviewed Departments
Scope and Number of Observations of Studies Reviewed Degree of Observations Clinical Trial Billing
Regulatory
and
Essential
Documents
Participant
Files/
Informed
Consents
Protocol
Procedures
Study/Source
Documentation
-Case Report
Forms
Pharmacy/
Drug
Accountability
Study/Safety
Monitoring-
Reportable
Events-
UPIRSOs and
Adverse
Events Other
Number
of
Critical
Number
of
Major
Number of
Minor
Total PI/Dept.
Observations
Number of
Studies
Reviewed
Percent
Exception
Rate
Requiring
Refund/Rebil
l
Dept A 1 1 0 0 0 0 0 0 0 2
2
N/A N/A
Dept B 0 0 0 2 0 1 0 0 0 3
3
N/A N/A
Research Observations
Reviewed Department
Regulatory
and Essential
Documents
Participant Files/
Informed Consents
Reportable
Events-
UPIRSOs and
Protocol
Deviations
Study/Source
Documentation-
Case Report
Forms
Pharmacy/Drug
Accountability
Study/Safety
Monitoring-
Reporting Other
Degree of
Observation
Dept A
Legal Authoritive Representative
was not specified on the
Informed ConsentMinor
Dept A
Required sponsor
training was not
documented for
approved study
staff
Minor
Dept B
Adverse Events were
not assessed for Clinical
Significance by the
Principal Investigator
Minor
Dept B
CRF/Study worksheets
were not signed by the
person obtaining the
study informationMinor
Dept B
Inappropriate
corrections were made
to the CRF/Study
worksheets
Minor
Data Trends
Consequences of
Non-compliance
• Safety risk to participants
• Jeopardize reliability of study data
• Negative Publicity
• Fines & penalties
• Legal fees & settlement costs
• Loss of public trust in clinical research
• Suspend research for PI or whole
institution
Consequences of
Non-compliance
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Focus Areas
&
Common Findings
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Regulatory Documents
• Submit progress reports to IRB on
time to prevent lapse in approval
• Check progress report for errors
• Comply with reporting requirements
for protocol deviations/adverse
events/UPIRSOs
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• Check IRB stamp for most current
consent version date
• Fill in signatures & time (AM/PM)
• Obtained by a person approved by IRB
• Evaluate the need for translation
• Document consent process in a
progress note
Informed Consent
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• Follow your protocol/plan
• Document eligibility for
participation (i.e. use a check list for
inclusion/exclusion criteria)
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Inclusion/Exclusion
Criteria
Protocol
Compliance
• Follow your protocol/plan
• Visit/Survey Frequency, Study Forms,
Scope of Data, Sites/Locations
• Submit any amendments to the IRB
• Track/document deviations or
missing data
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Documentation
• Correct data appropriately
• Sign and date forms
• Check for transcription errors from
source documents to database or
case report forms (CRFs) to sponsor
• Keep electronic files on a secure
server and paper documents in a
secure location
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Investigational Product
Accountability
• Drug dispensing/accountability log
• Maintain temperature/storage log
• Dispense by a person approved by IRB
• Have documentation of instructions for Investigational Product use (dispensing, returning & disposal)
PI Oversight of Study
• Local policies
• Conduct the study as
approved by sponsor and IRB
• Ensure staff is qualified and trained
• Review adverse events and
deviations
• Be ready for monitoring/inspections
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SELF ASSESSMENT
Practicing Good Clinical
Practice
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Things change. Be inspection ready!
Used with permission from Don Mayne. Wretched Mess Research Cartoons(2009)
Self Assessment
Basic Questions to Ask:
1. Is it research? Do I need IRB
approval? http://research.uthscsa.edu/irb/forms_NewResearch.shtml
2. What regulations and policies
apply?
3. Am I following the IRB approved
protocol/study plan?
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Self Assessment
• Request copy of compliance
review tool
• Review the OCR’s Documentation
Standards
• Principal Investigators - Check
participant charts and consent
forms
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“Quality means doing it right when no one is looking ”
Henry Ford
Good Clinical Practice
• Keep enrollment log up to date
• Maintain regulatory binder/file
• Document, document, document!
• Maintain adverse event and
protocol deviation tracking logs http://research.uthscsa.edu/irb/miscforms.shtml
• Promptly report non-compliance
and UPIRSOs to the IRB
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• Failure to follow the protocol
• Inadequate and inaccurate records
• Failure to report adverse events
• Failure to report concomitant therapy
• Inadequate drug/device accountability
• Lack of training/qualifications records
• Informed consent issues
• IRB problems (approvals)
Common Findings
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Regulations & Policies
• FDA Regulations (Title 21 Parts 11,
50, 54, 56, 312, 812)
• The Common Rule (Title 45 Part 46)
• Good Clinical Practice (GCP)
• Sponsor Policies (Industry, HHS)
• IRB / Institutional Policies
• AAHRPP
• HIPAA
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Privacy & HIPAA – What do
you need to know?
Kathy James
Assistant Compliance Officer
Assistant Privacy Officer
HIPAA Incidents
• Notification to the Privacy Office
(ORAC) of any incident
• IRB will request overview of CAPA
by the Privacy Office
• Information Management Services
will assist in review of data storage
HIPAA Incidents
• Accessing a patient record without
the need to know for your job
(FairWarning audit trail)
• Discussing subject identity in open
areas
• Sensitive study advertisements with
contact email not a “uthscsa” email
domain
• Sending subject identifying data
external in unencrypted email
HIPAA Incidents
• Mobile devices being used to store
subject data not encrypted
– All laptops need encryption-no
university data on personal laptops
– Cell phones with university emails
need to be password protected and
registered with IMS (MDM-Mobile
Device Management)
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HIPAA Incidents
• Posting subject/patient information
on social media sites, i.e., Twitter,
Facebook, SnapChat, Instagram,
etc.
– More of the 18 identifiers posted than
you think
– Lose of confidence with our subjects
– Reflects badly on the university
HIPAA Incidents
• Storing research data with
subject/patient information on
clouds, i.e., DropBox.
– Clouds not approved by IMS are not
secure
– No automatic back-up and data could
be lost
– Data is not easily retrievable if needed
(no administrator)
Use of Social
Security Numbers
• Required Notices for Disclosure –http://uthscsa.edu/compliance/RequiredNoticeSSN.asp
• Handbook of Operating Procedures –
Section 2.2.7
• Approved Notices for Disclosure –http://uthscsa.edu/compliance/RequiredNoticeSSN.asp
Utilize Resources
• Attend IRB Forums
• Visit IRB, CTO (New Clinical Trial
Office) and OCR websites for
updates, forms, and policies:
http://research.uthscsa.edu/ocr/index.shtml
http://research.uthscsa.edu/irb/
http://research.uthscsa.edu/cto/index.shtml
http://research.uthscsa.edu/ocr/1%203%201%
20Documentation%20and%20Data%20Mngt
%20v2.1%20w%20Matrix.pdf
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Office of Regulatory
Affairs & Compliance
ORAC Office: (210) 567-2014
Anonymous Compliance Line
1-877-507-7317
http://www.uthscsa.edu/compliance/
Gail Madison-Brown, [email protected]
Kathy James, [email protected]
Frank Estala, [email protected]
Clara Vorpahl, [email protected]
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Used with permission from Don Mayne. Wretched Mess Research Cartoons(2009)