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ETHICAL ISSUES in CR AND Inspections of Clinical Trials.
ETHICAL ISSUES in CR AND Inspections of Clinical Trials.
ISSUES
Dr. N. SRINIVAS
ICRI
1
ETHICAL CONSIDERATIONS &
ISSUES
Individuals involved in ethical issues
2
Individuals involved in ethical
issues
Investigators
Notify any relevant findings- revised ICF
Occupation
13.Continuation protocols
2. Protocol violations
Cont…
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Inspections…
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Inspection
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What are the results of inspection?
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How FDA Trains Inspectors
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FDA Inspections of Investigators
Purpose:
Determine that the rights, safety and welfare of
subjects have properly been protected
Assess adherence to FDA regulations and statutory
requirements
Determine quality and integrity of data submitted in
support of products pending FDA approval
The inspectors are employed by the Bioresearch
Monitoring Division as opposed to the persons who
give approval to do the study and who approve the
PMA for market release
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Permitting FDA Inspections:
Investigators and Sponsors
Regulations require that sponsors and investigators
grant access to authorized FDA employees
Any location where devices are manufactured, processed, packed,
installed, used or implanted or where records of use/results are kept )
Records Inspection -
Sponsor, IRB, Investigator (or anyone acting on their behalf)
will permit authorized FDA employees to inspect & copy all
records relating to an investigation.
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FDA Inspections of Investigators
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Reasons for Inspecting an Investigator
Could Include:
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Investigator Deficiencies: FY 2000-2004
45 41 41
40
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30
25
20 15
15 9
10
5
0
FY2001 FY02 FY03 FY04
Reference: “Building Quality into Device Clinical Trials”,
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Medical Alley, April 20, 2005
Preparing for Inspection
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When the FDA calls for Inspection:
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Conduct of Inspection
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Conduct of Inspection cont.
Interview Guidelines:
Do not engage in conversation unless asked a direct
question
Restrict statements to answering those questions
asked by the FDA Investigator
Do not provide excuses or shift blame (either on previous
employees, staff members, IRB)
Do not guess at answers – If uncertain of correct answer,
obtain the correct information and provide to the FDA
Investigator
Do not answer questions which lie outside the authority of
the Inspector (sales data, personnel information relating
to salaries, performance reviews, etc.)
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Conduct of Inspection: Interview
Guidelines cont.
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Conduct of Inspection cont.
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Conduct of Inspection cont.
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Conduct of Inspection cont.
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Finding from a 2003 Warning Letter to an investigator:
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Conduct of Inspection cont.
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Findings from a 2002 Warning Letter an Investigator:
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Conduct of Inspection cont.
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Study Documents Required for the
Inspection Will Include:
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Study Documents Required for the
Inspection Will include cont.
7) Training records of all site personnel involved in
trial
8) Source documents for CRF entries, prior medical
history, condition of the subject at the time of
entry into study, meds, if required by study,
laboratory reports, and any special testing per
protocol.
9) Documentation for any correction to CRFs
10) All correspondence, records, & reports
11) Investigational device/drug accountability
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Finding from a 2003 Warning Letter to an investigator:
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Finding from a 2003 Warning Letter to an investigator:
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What Happens After an Inspection?
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What Happens After an Inspection cont:
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Evaluation to Classify and Mail
Prompt Letter to Investigator
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Evaluation to Classify and May
Prompt Letter to Investigator cont.
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Investigator Non-Compliance
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In Conclusion….
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483 Finding from a 1999 Investigator Inspection:
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Spectrum of QA Metrics
Human
Short cuts
Errors
Deliberate invention
Exaggeration
Carelessness
NEGLIGENCE FRAUD
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Strange but True!
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"The bitterness of poor
quality remains long after
the sweetness of meeting
the deadline has been
forgotten”
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