Compliance at CUMC January 26, 2012 Monthly IRB-Investigator Meeting Common Noncompliance Findings and

Monthly IRB-Investigator Meeting
Compliance at CUMC
Common Noncompliance Findings and
How to Avoid Them
January 26, 2012
George Gasparis
Executive Director, HRPP/IRB
Jessica Randall
Compliance Oversight Manager
Objectives
Today’s session will provide insights on:
• Overview of Columbia’s Compliance Oversight Program
• Process for Handling Allegations of Non-Compliance
• Definition of Serious Non-Compliance
• Reporting to the IRB, Federal Agencies
• Common Findings
• Corrective Action Plans
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Event Reminders
Save the Date:
Regular Events
Thursday, February 22, 2012
(3:30-4:30): MIM
Office Consultation Hours:
(Todd Amphitheatre – P&S 16-405)
– ClinicalTrials.gov with the
Clinical Trials Office (CTO)
Tuesday, April 10, 2012: IRB
101 (10:00-2:00)
(Alumni Auditorium - Black Building)
Annual IRB Education
Conference: Monday-Tuesday,
May 7-8, 2012
(Lerner Hall – Morningside Campus)
Tuesdays 10:00-11:00 in the
IRB Office (722 W. 168th St.,
MSPH, 4th floor)
RASCAL Workshops: every
other Tuesday 3:30-4:30
(Hammer 202A Computer Lab)
– 1/31: Renewals/Modification
– 2/14: Consent
– 2/28: New Protocols
January 26, 2012
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General Announcements
IRB Administrative Quiet Hours: Monday-Friday, 11:00-1:00:
– call 212-305-5883 with urgent issues during this time.
Education Requirements:
– CITI 3 year re-certification will be starting in March for those completed 3+
years ago
Like us on Facebook! Follow us on Twitter!
– http://www.facebook.com/ColumbiaIRB or @ColumbiaIRB
January 26, 2012
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Compliance Oversight Program
The Columbia Oversight Team handles the following
oversight activities:
-all reporting requirements under 45 CFR 46 and FDA
regulations;
-investigation of allegations of noncompliance;
-conducts not-for-cause audits;
-also investigates IRB review of the study.
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Compliance Oversight Program (cont’d)
The Columbia Oversight Team handles the following
oversight activities:
-review of all subject complaints reported to the IRB;
-review results of external monitoring activities and
maintain repository of reports (e.g., FDA, NCI
oncology-group studies, etc.);
-provides guidance/consultation for FDA audits;
-provides consultation for corrective action plans.
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Compliance Oversight Team (COT)
Jessica Randall – COT Manager
Vanessa Laroche – IRB Auditor
Diana Wong – IRB Auditor
Dan Matulich – IRB Auditor
George Gasparis – Director
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Comply with what?
Standards for Human Subjects Protections
•Ethical Principles
Belmont Report, Declaration of Helsinki
•Federal Regulations
-HHS Regulations - 45 CFR 46
-FDA Regulations – 21 CFR 50, 56, 312, 600, 812
-Privacy Rule
-NY State Law – Article 24A (2440-6); Article 7 (79-1)
•Federal Guidance – (e.g., Good Clinical Practice)
•Institutional Policies
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Basic Regulatory Requirements for
Investigators – 45 CFR 46 (HHS Regulations)
ABCs of regulations
All federally supported human subjects research must ensure:
• A – Assurances of Compliance for all performance sites
• B – Board approval (IRB, ethics cmte., research ethics board)
• C – Consent from every subject (unless waived by the IRB)
• D – Disclosure - reporting of serious noncompliance, unanticipated
problems involving risks to subjects or others, suspensions or
terminations
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Serious noncompliance may include, but is not limited to:
1) failure to obtain or maintain IRB approval before
conducting any research involving human
subjects/conducting research during a lapse in approval;
2) enrollment of subjects without obtaining legally-effective
informed consent
3) failure to report serious and unanticipated problems
involving risks to subjects or others in accordance with
institutional policy;
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Serious noncompliance may include, but is not limited to
(cont’d):
4) implementing a substantive modification prior to
obtaining IRB approval;
5) significant violations of the protocol;
6) ongoing noncompliance.
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45 CFR Part 46.103(b)(5) & 21 CFR 56.108(b)
Written procedures for ensuring prompt reporting
to the IRB, appropriate institutional officials, and the Department or
Agency head (and FDA when applicable) of:
(i) any unanticipated problems involving risks to subjects or others;
(ii) or any serious or continuing noncompliance with this policy or the
requirements or determinations of the IRB; and;
(ii) any suspension or termination of IRB approval.
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Columbia University Policy
All potential noncompliance with regulations, or
University policy, for the protection of human
subjects in research must be promptly reported to
the IRB.
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Concerns about possible Research Noncompliance may be
discussed with an IRB Chair, the Executive Director of the
IRB, the Associate Director of the IRB, or the Manager of
the Compliance Oversight Team.
Any individual may make an allegation of Noncompliance.
Any such allegation shall be documented in writing and
given to the Executive Director or Associate Director of the
IRB.
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NOTIFICATION TO REGULATORY AGENCIES OR
FUNDING SOURCES
The IRB will report noncompliance to:
-designated IRB;
-institutional officials, deans, department chairs;
-legal counsel;
-the appropriate regulatory agencies (e.g., OHRP,
FDA, etc.) and sponsors.
January 26, 2012
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TOP TEN AUDIT ISSUES
10. Regulatory Binders (or folders for regulatory
approvals) are not appropriately maintained.
-See Clinical Research Handbook for guidance
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TOP TEN AUDIT ISSUES
9. “Documentation?
What documentation?”
Lack of documentation
– Missing source documentation
– Keep notes on everything
– Have a standard notes page
– Document the visit dates, when consent was obtained, any questions
answered, anything of interest – chronological order
– Over time, staff and co-investigators change - documentation is critical
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TOP TEN AUDIT ISSUES
8. Organization of records
“It’s time for my continuing review and I can’t find my protocol
and/or consent form- can you send it to me?”
– Put every document file location in the footer of documents so you will
know where to find it.
– Give the documents reasonable titles with version #’s
– (i.e. ‘Study 9892, Version Date 01/03/12’ is a good title. ‘Blood study protocol’ is
bad. Need version #’s or dates)
– Keep protocol documents together in one folder and clearly marked in
one folder on the network. Let your supervisor and those involved in
data collection/management know where it is/grant access
– Back-up your files regularly (i.e. M-F 4:45pm, every Friday 4pm, etc.)
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TOP TEN AUDIT ISSUES
8. Organization of records
“It’s time for my continuing review (cont’d)
– Confirm the number of subjects enrolled, completed, withdrawn,
dropped out, etc.
– Account for all modifications that have been made or need approval
– Account for safety monitoring over the past year and ensure that all
UPs had been reported
– Account for progress reports; if SI study, annual update to FDA.
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TOP TEN AUDIT ISSUES
7. “Did I say that?”
Not sticking by the recruitment plan set forth
in the IRB protocol
– Make recruitment plans clear and provide details and then
follow the plan.
i.e., ‘We will post fliers in the Emergency Department (flier
attached) and we will call subjects who previously participated
in IRB protocol # 0099-101 that agreed to be contacted for
future research studies (see phone script attached).’
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TOP TEN AUDIT ISSUES
6. Design
study protocols carefully
• The IRB protocol is the exact plan you will be abiding by for the
duration of the study (unless you submit an amendment). Any
variation from that plan needs to be reported as a ‘deviation’ or
‘violation.’
• Study visits should be planned around safety monitoring and
scientific needs for the study with consideration of appropriate
study visit windows to minimize deviations.
• Do the same for everyone in the same situation across the
board
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TOP TEN AUDIT ISSUES
6. Design
study protocols carefully (cont’d)
• Create appropriate inclusion and exclusion criteria that meet the
scientific needs of the study and that consider feasibility.
• Provide clear endpoints and rules for changing dosages for
management of toxicity
• Carefully select the type and frequency of study procedures that
with consideration of feasibility
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TOP TEN AUDIT ISSUES
5. “My Coordinator Left Me and Now My Study’s A Mess”
(sounds like a bad country song)
• The Principal Investigator is ultimately responsibility for the study.
You play your part, but they need to be in the know.
• Appropriate resources
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TOP TEN AUDIT ISSUES
4. Using non IRB-approved documents (fliers, brochures,
phone calls, e-mails)
- need a script- altering even a number on a flier needs to be
re-approved by the IRB (expedited most times)
– Changing a number on a flier? Send it back to IRB for re-approval/re-stamping.
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TOP TEN AUDIT ISSUES
3. Failure to obtain legally-effective consent and/or HIPAA
Authorization
Obtaining consent is a PROCESS (IRB consent and HIPAA
authorization) not just a signature.
– Have an effective consenting process. Spend more time on subject
questions now, have less problems later.
– i.e. subject was mailed a page of their consent form
– Subject signs and dates and PI/co-I then signs and dates- dates need
to match!
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TOP TEN AUDIT ISSUES
3. Failure to obtain legally-effective consent and/or HIPAA
Authorization (cont’d)
•HIPAA Authorization form and IRB consent form are not signed at the
same time and/or the Authorization form is signed after a portion of the
study is completed.
-Before you collect any data make sure every subject signs both forms at the
screening before ANY procedures take place or any questionnaires are completed.
•Non IRB-approved forms are signed.
•Check boxes for additional tests/samples/procedures not checked or
initialed.
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TOP TEN AUDIT ISSUES
2. Failure to obtain IRB approval
-initiation of any research related activities prior to IRB
approval.
-conducting research related activities during a lapse in
IRB approval;
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TOP TEN AUDIT ISSUES
1. Know your Limitations
Keep an open dialogue with the PI (s/he is ultimately responsible for their study)
keep a detailed calendar and notes - document everything!
Set weekly meetings with your supervisor.
Don’t know the answer? Ask or call the IRB or Compliance Manager. Rather ask
now than have issues later.
“Yeah…I’m going to need
you to come in on
Saturday…
and Sunday too…”
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Common Findings
•Initiation of research prior to IRB approval or signing of contract
•Enrollment/research activities during lapsed periods;
•Over-enrollment beyond FDA or IRB-approved sample size
•Failure to use the IRB-approved consent form
•Use of an expired IRB-approved consent form
•Failure to obtain legally-effective consent
•Inappropriate signatures and/or dates on the consent document
•Failure to file signed consent document in medical record
•Lack of or incorrect HIPAA form
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Common Findings (cont’d)
•Lack of documentation (i.e., source documents; research procedures;
documentation of consent process)
•Subject did not indicate/initial choice (yes or no) for additional tests or
samples to be held for future purposes.
•Failure to follow the protocol
•Failure to satisfy inclusion/exclusion criteria
•Failure to obtain Sponsor and IRB approval for eligibility waivers
•Failure to report unanticipated problems promptly to the IRB
•Failure to report SAEs to the sponsor (and FDA for investigator held
IND/IDE studies)
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Common Findings (cont’d)
•Failure to obtain IRB approval of modifications
•Failure to maintain drug accountability records
•Unauthorized personnel ordering study drug
•Unauthorized personnel administering study drug
•Unauthorized personnel performing clinical procedure
•Failure to protect confidentiality/privacy of study data in accordance with
the protocol;
•Inappropriate access to medical records
•Conducting research without appropriate training
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General Considerations for Corrective Action Plans
•
Account for noncompliance findings
•
Conduct root-cause analysis
•
Develop processes that will prevent future noncompliance
•
Consider ability to implement and maintain new process
•
Consider burden of maintaining new process
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Most Serious Finding of Noncompliance –
Failure to Obtain IRB Approval
-Key is understanding how to apply the definitions of
“human subject” and “research”
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When Does Human Subjects Research
Need IRB Review?
Not Human Subjects
Research
QA
No IRB Review
Needed
HHS Regulations
Human Subjects Research
Training
that is not exempt
Evaluation
Needs IRB Review
Surveillance
Basic Science
Polling
(Exempt Research Needs Determination of Status by IRB)
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Columbia IRB
Mission - Facilitate the Ethical Conduct of Research
Education Training
Compliance Oversight
Join the IRB Listserv
Consultation Hours
Service-oriented
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Education Training
Required Training:
• Completion of CITI Web-based training modules
• Research with Minors
• FDA –regulated research
• Continuing education requirement (March 2012)
• Columbia HIPAA training module
• Clinical Research Coordinator training (October 2010)
• Sponsor-Investigator training
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Columbia IRB Websites:
-CUMC http://www.cumc.columbia.edu/dept/irb/
Children as Study Subjects in Research:
http://www.cumc.columbia.edu/dept/irb/policies/index.html#irb
-CU IRB http://www.columbia.edu/cu/irb/
Children as Study Subjects in Research:
http://www.columbia.edu/cu/irb/policies/index.html
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