Transcript No Slide Title

Overview of Good Clinical
Practices (GCPs)
Barbara Pennington, RN, MS
PPD
Why Regulate Clinical
Research?
Ensure the rights, safety, and wellbeing of participants
Scientific Integrity of data
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Good Clinical Practices
(GCPs)
Standards for designing,
conducting, performing, monitoring,
auditing, recording, analyzing, and
reporting clinical trials.
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GCP
FDA
21 CFR
• Electronic Docs.
• Inf. Consent
• $ Disclosure
• IRBs
• IND regs.
OHRP
ICH
45 CFR 46
International
• IRBs
• Inf. Consent
•Women
•Prisoners
•Children
• glossary
• principles
• IRBs
• Investigator
• Sponsor
• Essential Docs
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U.S. FDA
(Food and Drug Administration)
Branch of the United States
Department of Health and Human
Services
Regulates all aspects of
pharmaceutical industry
Title 21 of the Code of Federal
Regulations (CFR)
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CFR Title 21
Parts applicable to clinical research:
Part 11 - Electronic Records and Signatures
Part 50 - Protection of Human Subjects
Part 54 - Financial Disclosure by Clinical Investigators
Part 56 - Institutional Review Boards
Part 312 - Investigational New Drug Application
Part 314 - Applications for FDA Approval to Market a New Drug or
an Antibiotic Drug
Part 600 - Biological Products
Part 812 - Medical Devices
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Form FDA 1572
Contract between FDA and
Investigator
Logistics such as names and
addresses
Section 9
Commitments of the Investigator
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Investigator of Record
(IOR) Agreement
For Non-IND studies
Identifies key personnel, facilities,
labs, IRBs
Also lists the commitments of the
investigator
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Commitments of the IOR
Comply with protocol
Ensure compliance of IRB and consent
process with 45CFR 46
Report AEs
Accurate record keeping and access
No changes to study without
permission of Sponsor and IRB
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This is a Non-IND Study
Do we have to
worry about FDA?
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Office for Human Research
Protections (OHRP)
OHRP responsible for ensuring the
safety and welfare of people who
participate in HHS sponsored research
Under the DHHS Assistant Secretary of
Health
45 CFR part 46
Formerly OPRR
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45 CFR part 46
IRB
Informed Consent
Protection of Fetuses, Pregnant
Women
Protection of Prisoners
Protection of Children
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45CFR 46 Subpart A
The “Common Rule”
Protection of Human Subjects
IRB/IEC
Informed Consent
Variations from FDA Regulations
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45CFR 46 Subpart B
Protections for Pregnant Women,
Fetuses and Neonates
Definitions
Recent revisions
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45CFR 46 Subpart C
Additional Protections for Prisoners
involved in research
Definition of Prisoner
Additional IRB Duties
Permitted Research
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45CFR 46 Subpart D
Additional Protections for Children
involved in Research
Assent
Minimal risks
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International Conference on
Harmonisation (ICH)
Guidelines for Good Clinical Practices
Objectives of ICH
guidelines
Provide a unified standard
EU; US; Japan
To facilitate mutual acceptance of
clinical data
Developed in accordance with
existing standards in US, EU, Japan,
Australia, Canada, Nordic Countries,
and WHO
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ICH GCP
Consolidated Guideline E6
Glossary
Principles of ICH GCP
Information regarding:
IRB/IEC
Investigator
Sponsor
Protocol
Investigator’s Brochure
Essential Documents
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Principles of ICH GCP
Conduct trials according to GCP
Weigh risks vs. benefits
Protect the subjects
Have adequate information to justify
trial
Write a sound protocol
Receive IRB/IEC approval
Use qualified physicians
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Principles of ICH GCP
Use qualified support staff
Obtain informed consent
Record information appropriately
Protect confidentiality
Handle investigational products
appropriately
Implement quality systems
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Local Regulations
May have more detailed regulations
that apply locally
Do not conflict with national
regulations
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Sponsor Policies
US Department of Health and Human
Services
NIH/DAIT/DAIDS
Essential Document and Source Document SOP
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Internal SOPs
Standard Operating Procedures
(SOPs)
Detailed instructions describing the what,
when, where, and by whom of
performing an activity
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Compliance =
Adherence to
GCPs
Sponsor policies
local regulations
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Investigator
Responsibilities
Investigator
Responsibilities*
Investigator Qualifications and Agreements
qualified by education, training and experience
familiar with protocol, IB, IP
aware of and compliant with GCPs and applicable regs
permit monitoring
list of qualified personnel who are delegated duties
*(ICH 4.1-9)
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SAMPLE
Delegation of Responsibility Log/Signature List
Study:
Investigator
Name
Name and Title of Site Staff
Site Number
Signature
Responsibilities*
Involved
From
Involved To
(See below)
DD-MMM-YY
DD-MMM-YY
Initials
Use Block Capitals
A
B
C
D
E
F
G
H
I
A
B
C
D
E
F
G
H
I
A
B
C
D
E
F
G
H
I
A
B
C
D
E
F
G
H
I
A
B
C
D
E
F
G
H
I
A
B
C
D
E
F
G
H
I
A
B
C
D
E
F
G
H
I
DELEGATION OF RESPONSIBILITIES CODES
NOTES FOR COMPLETING THIS FORM
A.
B.
C.
D.
E.
F.





Obtaining consent
G. IP Receipt/Return
CRF entries
H. Query Resolution
Dispensing Medication
I. Authorized Signatory for
Physical Examination
resolved queries
Phlebotomy
J. Other_____________
Essential Documents
*Delete those which do not apply
Page
Number
PI Initials
Please PRINT CLEARLY when completing this form
Please enter all dates in the DD-MMM-YY format (e.g., 21-JAN-01)
Use ‘Involved From’ and ‘Involved To’ to record staff changes during the study
Enter a new line and applicable dates when responsibilities change
PI should initial each line as individuals are assigned responsibilities
Principal Investigator Signature (Close Out):_______________________________________
Date:_____________________________________
Investigator
Responsibilities*
Adequate Resources
recruit adequate subjects
sufficient time
qualified staff and adequate facilities
Medical Care of Subjects
responsible for all trial related medical decisions
*(ICH
4.1-4.9)
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Investigator
Responsibilities*
Communication with IRB
approvals
ensure compliance
Compliance with Protocol
Investigational Product (IP)
proper delegation of duties
*(ICH 4.1-4.9)
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How can the PI be held
responsible for what the IRB
does or does not do?
Document ALL interaction (verbal, electronic, written) with IRB
including reminders of upcoming review requirements
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Investigator
Responsibilities*
Regulations require IRB is aware of
changes in research activity
“…OHRP finds that changes to research
protocol were implemented by
investigators without IRB approval…”
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Investigator
Responsibilities*
Randomization & Unblinding
Informed Consent
Records and Reports
ensure accuracy, completeness, legibility and
timeliness of data
data on CRF derived from Source Documents
changes made appropriately
allow direct access
*(ICH
4.1-4.9)
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Regulatory Authorities will
inquire about:
Source of study subjects
Did they have the disease under
study
Did they meet inclusion/exclusion
criteria
Was the protocol precisely followed
Were AEs reported appropriately
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Common OHRP Findings
IRB failed to review the research at a
convened meeting
failure to review grant applications
Investigators failed to promptly report
unanticipated problems involving risks
to subjects to IRB, OHRP and Sponsor
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Common OHRP Findings
Continuing review of research was
NOT substantive nor meaningful
include a summary of AEs and unanticipated
problems
# of subjects accrued
summary of recent literature, findings
amendments, modifications since last review
relevant reports, information
current consent form
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Common OHRP Findings
IRB did not ensure additional
protections for vulnerable subjects
IRB members with conflicting interest
participated in review
IRB meeting convened without
Quorum (Non-scientist absent)
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Common OHRP Findings
IRB review of NIH approved consent
any changes to the sample consent form
related to risks or alternative procedures must
be justified in writing by the investigator,
approved by IRB and reflected in the IRB
minutes
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OHRP Finds that the IRB:
Lacks diversity
is overburdened by large volume
level of staff support is insufficient
members lack detailed understanding
of regs. for protection of human
subjects
inadequate procedures for reporting of
unanticipated problems
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We Applaud COMPLIANCE
GCPs
Protocol
DAIT/DAIDS
procedures
Local regulations
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