Common Mistakes
& Audits
05/21/2014
Summary of audit
findings by
category
Discrepancies in Documentation of Informed Consent
Protocol Deviations
Personnel Changes Not Reflected in Study Documentation
Discrepancies in Reporting Adverse Events to IRB
Errors made by IRB
Lack of Required Training
Deviations from Good Clinical Practice
Disrepancies in Subject Data
Other
0
10
20
30
40
50
Common Mistakes
• Delegating responsibility rather than
authority
• The PI is always responsible for all study
activity and for all personnel
performance
Lesson to be learned….PI
Pick your sub-investigators and
coordinators carefully!
Common Mistakes
• Informed Consent
This is the Achilles heel of research and is
the most commonly cited in litigation
Common Mistakes
• Not keeping the IRB informed of study
changes and updates
Especially in sponsored research we have a
sponsor that continually monitors study
activity- it is a common mistake to notify the
sponsor of problems and forget to notify the
IRB
Common TTUHSC
Audit Findings
• Discrepancies in executed Informed Consent
Documents, such as:
– Person signing as PI/Authorized Representative is
not authorized to sign
– PI/Authorized Representative fails to date
– PI/Authorized Representative signature date
different than Subject signature date
– Most recent IRB-approved Informed Consent
Document not utilized (old form is used)
Common TTUHSC
Audit Findings
Common TTUHSC
Audit Findings
• Serious Adverse Events not reported to the IRB promptly (for
example, SAE reporting to the IRB done months later at the
request of the sponsor)
• No source documentation available to verify that the subjects
received a copy of the Informed Consent Document
• Signed original Informed Consent Documents not
consistently stored in the same location (for example, a
majority of originals are found in the individual subject
binders and a few originals are found in the medical record)
• Investigators and/or research staff lacking TTUHSC human
research protection training and/or HIPAA for Researchers
training
• Failure to submit amendments to the IRB regarding protocol
modifications or changes in investigators and research staff
Common TTUHSC
Audit Findings
• Subject reimbursement procedures.
• Non-research staff involved in the research process.
Sponsor Audits
• Purpose: to evaluate trial conduct and
compliance with the protocol, SOPs, GCP,
and applicable regulations
• A sponsor’s audit is independent and
separate from routine monitoring or quality
control functions
• Should be done by individuals who are
independent of the clinical trials/systemsregular Monitor can’t do them.
FDA Audits
• Purpose: To ensure compliance
Type of Audits
• Study-directed audits
• Investigator-directed audits
• For cause audits
• Not for cause audits-routine surveillance
What FDA Looks For
•
•
•
•
•
•
•
Who did what
Degree of delegation
Where study was performed
How/ where data were recorded
Drug accountability
Monitor contact & follow-up letters
Data audit
FIRST binder they ask for may be correspondence!
Recent FDA Findings
• Inclusion of individuals that did not meet the
inclusion criteria.
• Continuing of individuals that should have
been removed from the study.
• Study procedure errors (not following the
study roadmap)
• Errors in dosing
• Communication errors
What if the FDA
shows up?
•
•
•
•
•
•
•
Do NOT panic!
Ask for their ID and Form 482
Give them ONLY what they specifically ask for
Try never to leave them alone
Put them in a room that has no other study materials
Be honest and helpful
Notify the Human Research Protection Office (HRPO)
at TTUHSC-In advance if possible
• Notify the study sponsor-in advance if possible
FDA Audits
• FDA 482-Notice of Inspection (they’re coming)
• FDA 483-Audit findings (BAD! Issued if they note
some kind of problem, you may or may not get a
warning (action) letter with it)
• Establishment Inspection Report (EIR). This is an
overall report of their visit-you’ll always get this.
• Action Letters:
NAI-No Action Indicated
VAI-Voluntary action indicated
OAI-Other action indicated
The Corrective
Action Plan
• PI MUST take responsibility
– Do not play the Pass the Blame Game!
• Address each issue directly
• Enlist the help of your sponsor and local
compliance team
FDA Regulatory
Sanctions
•
•
•
•
Formal disqualification
Clinical hold
Voluntary restrictions
Criminal prosecution
Long-term
consequences
• Audit results are publicly accessible on the FDA
website
• Only bad conduct makes the news-front page
• Most pre-study questionnaires from sponsors ask if
you’ve ever been audited, received a 483. If you
have they want a copy.
• Effects your reputation in the clinical research arena
– Your commitment & ethics may be questioned
Points to
Remember
• Audit Findings/Common Mistakes – The
Informed Consent is most commonly cited in
research litigation
• The PI is always responsible for all study
activity and for all personnel performance
• Keep the IRB informed of all study changes
and updates
QUESTIONS?