Transcript Document

Good Clinical Practice
A Review for OCRA US RAC Study Group
September 2005
Ginger Clasby, MS
Promedica International
[email protected]
714-799-1617 x 25
GCP
What It Is
• An international ethical & scientific quality standard for
designing, conducting, recording & reporting human
clinical studies
– EU
– Japan
– US
• Applies to registration studies that may have an impact
on safety & welfare of human subjects
GCP
Participating Parties
• IRB/Ethics Committee
• Investigators
• Sponsor
• Regulatory Authorities
GCP
Key Documents
• Investigator Brochure
• Study Protocol
• Informed Consent Document
GCP
Principles
1.
Studies in accordance with Declaration of Helsinki;
consistent with GCP & applicable regulatory
requirements
2.
Studies initiated & continued only if anticipated
benefits outweigh risks
3.
Rights, safety & welfare of human subjects take
priority over interests of science & society
4.
Available non-clinical & clinical info on product
adequate to support study
GCP
Principles
5. Studies scientifically sound; described in clear,
detailed protocol
6. Study in compliance with IRB/EC approved protocol
7. Medical care given to subjects is the responsibility of
qualified medical professional(s)
8. Individuals conducting studies qualified by education,
training & experience
9. Freely given informed consent obtained from every
subject prior to study participation
GCP
Principles
10. Study information recorded, handled & stored to
allow accurate reporting, interpretation & verification
11. Confidentiality of subject records protected in
accordance with applicable regulatory requirements
12. Investigational products manufactured, handled &
stored in accordance with GCP & used in accordance
with approved protocol
13. Systems/procedures implemented to assure quality of
study
IRB/EC
Roles & Responsibilities
To safeguard study subjects’ rights & welfare by:
• Evaluation/disposition of study proposal
• Evaluation of proposed subject consent materials
• Evaluation of emergency use consent methodology
• Evaluation of investigator qualifications
• Ongoing review of study progress (at least yearly)
• Evaluation of proposed subject compensation plans
IRB/EC
Composition & Operations
• Membership has qualifications & experience to evaluate
science, medical aspects & ethics of proposed study
– ≥ 5 members
– ≥ 1 member whose primary interest in nonscientific
– ≥ 1 member independent of institution or study site
• Written SOPs & records
• Decisions rendered at announced meetings with
quorum in attendance
IRB/EC
Composition & Operations
• Only members participating in review should vote
• Investigator may provide info on study, but should not
be involved in review or vote
• Nonmembers with expertise in special areas may be
invited to assist with review (but cannot vote)
IRB/EC
Procedures
• Document group membership & qualifications
• Schedule meetings & notify members
• Conduct initial & ongoing review of studies
• Determine ongoing review frequency
• Provide expedited review of minor study changes, in
accordance with regulatory requirements
• Specify that no subject should be enrolled in study prior
to IRB/EC approval
IRB/EC
Procedures
• Specify that no deviations from protocol should be
initiated without prior IRB/EC approval
– Emergency situations require immediate notification of IRB/EC
after the fact
• Specify that Investigator should promptly report:
– Protocol deviations
– Changes increasing subject risk or study procedures
– Serious and unexpected adverse events
IRB/EC
Procedures
• Notify Investigator promptly of:
– Study-related decisions
– Reason for decisions
– Procedures for appeal of decisions
IRB/EC
Required Records
• Relevant records maintained ≥ 3 yr after study
completion
• Records available for review by regulatory authorities
IRB/EC
What is Reviewed
• Investigator Brochure or Report of Prior Investigations
• Study protocol & amendments
• Investigator qualifications
• Informed consent documents, including subject
recruiting tools
• Other written information provided to subjects
• Subject compensation plans
• Adverse events
• Protocol deviations
IRB/EC
When Reviews Occur
• Prior to study initiation at site
• At least yearly during study
• During study, as necessitated by:
– Changes in protocol, consent documents, etc.
– Changes in study investigator
– Reports of serious or unanticipated device-related
adverse events
• At study completion or termination
Investigator
Roles & Responsibilities
• Qualified to conduct study
• Have adequate resources to conduct study
• Provide medical care to study subjects
• Regular communication with IRB/EC reviewing study
• Compliance with study protocol
• Maintenance of investigational product accountability
• Compliance with study randomization & unmasking
procedures
• Provide informed consent to study subjects
Investigator Responsibilities
Appropriate Qualifications
• Training & experience demonstrated via:
– Medical license
– CV
– Specialized study training
– GCP training
• If study responsibilities delegated, need a list of
qualified persons to whom responsibilities are
delegated
Investigator Responsibilities
Adequate Resources
• Suitable staff & good methods for keeping them
apprised
• Suitable facilities
• Appropriate patient population
– Access to disease or condition
– Volume of patients with disease or condition
Investigator Responsibilities
Medical Care
• Make medical decisions regarding patient treatment
• Adequate care for study-related adverse events
• Diligence in ascertaining reason(s) for subject
withdrawals from study
Investigator Responsibilities
IRB/EC Communications
• IRB/EC approval prior to study initiation
• IRB/EC kept apprised of events & progress during study
Investigator Responsibilities
Protocol Compliance
• Conduct study in accordance with protocol
• May not deviate from protocol without Sponsor/IRB
approval
• Document deviations from protocol
Investigator Responsibilities
Investigational Product Accountability
• Maintain accountability at study site
• Document product receipt & disposition
• Maintain product in a secure area
• Use product only in accordance with protocol
• Disallow use of product by anyone not registered with
study
Investigator Responsibilities
Randomization Procedures & Unmasking
• Follow study randomization procedures
• Unmask only in accordance with protocol
• Document noncompliance or premature unmasking
Investigator Responsibilities
Subject Informed Consent
• Comply with regulatory requirements
• Update consent documents as necessary
• Inform subject that study involves “investigational”
product
• May not coerce subject to participate
• May not waive subject’s legal rights
• Keep subject informed of new information regarding
study
Investigator Responsibilities
Subject Informed Consent
• Provide informed consent in understandable language
• Give subject the chance to ask questions
• If subject can’t read, need impartial witness
• If subject is “disadvantaged”, need legally authorized
witness
• Get subject consent in writing prior to initiation of study
procedures
• Give subject a copy of signed consent document
Investigator Responsibilities
Required Records & Reports
• Essential regulatory document file(s)
– Protocol & amendments
– Approved informed consent documents
– Product accountability documentation
– Investigator qualifications & agreements
– IRB correspondence
– Study delegation list
– Subject screening/enrollment logs
– Study monitoring reports
– Calibration/maintenance logs
– Memos to file
Investigator Responsibilities
Required Records & Reports
• Source documentation
• Data capture forms (study-specific)
• Data clarification forms
• Fully executed informed consent documents
Investigator Responsibilities
Required Records & Reports
• Written periodic status reports to IRB/EC
• Written reports of protocol deviations to Sponsor &
IRB/EC
• Serious or unanticipated product-related adverse
events to Sponsor & IRB/EC
• Notification of study suspension or termination to
IRB/EC
• Final study report to IRB/EC
• Retain ≥ 2 yr
Sponsor
Roles & Responsibilities
• Study quality assurance
• Appropriately qualified medical personnel to advise on
study
• Utilization of qualified personnel in study design &
operations
• Study management, data handling & record keeping
• Investigator selection & training
• Definition/allocation of study responsibilities
Sponsor
Roles & Responsibilities
• Facilitation of communications between Investigators
• Study compensation (investigators and/or subjects) &
financing
• Regulatory authority notification/submission
• Confirmation of IRB/EC review/approval
• Investigational product information
• Investigational product manufacturing, packaging,
labeling & coding
• Investigational product supply & handling
Sponsor
Roles & Responsibilities
• Record access
• Ongoing safety evaluation & reporting
• Serious/unanticipated adverse event reporting
• Study monitoring
• Study noncompliance procedures
• Study termination or suspension notification
• Study reports
Sponsor
Roles & Responsibilities
• Sponsor may transfer responsibilities to CRO
– Transfer must be documented in writing
– Sponsor still has ultimate responsibility for study
quality and data integrity
Study Protocol
Components
• General administrative info
• Background
• Study purpose & objectives
• Study design
• Subject eligibility requirements
• How subjects will be treated
• How safety & efficacy will be assessed
• Sample size justification & statistical analysis methods
Study Protocol
Components
• How data will be captured & maintained
• Monitoring procedures
• Proposed informed consent document
Informed Consent Document
Components
• Statement that study involves “research” & product
“experimental” (if applicable)
• Study purpose
• Number of expected study subjects to be enrolled
• Study treatment(s) & probability for random assignment
• Study exams & procedures for duration of trial
• Subject’s responsibilities
• Foreseeable risks to subject (embryo, fetus, nursing
infant)
Informed Consent Document
Components
• Expected benefits
• Alternatives procedures or therapies & associated
risk/benefit
• Compensation available in event of study-related injury
or sickness
• Anticipated payments to subject for study participation
• Anticipated expenses to subject for study participation
• Statement that participation is voluntary
Informed Consent Document
Components
• Description of extent to which confidentiality can be
assured
• Commitment to keep subject apprised on new
information that may affect subject’s willingness to
participate in study
• Contact info for questions re: subject rights; trialrelated adverse events
• Circumstances under which subject’s participation may
be terminated
Investigator Brochure
What It Is
A compilation of clinical & non-clinical data on the product
that is relevant to the product’s study in humans
Necessary for Investigator & IRB/EC review to assess the
risks/benefits associated with study
Investigator Brochure
Components
Product formulation summary
Introduction/background info regarding product &
investigational plan
• Investigational product physical, chemical &
pharmaceutical properties & formulation
• Non-clinical studies
• Human clinical studies
• Summary of data & guidance for Investigator
Good Clinical Practice
Reference Documents & Links
• ICH - E6: Guideline for Good Clinical Practice
• 21 CFR 50 - Informed Consent
• 21 CFR 56 - Institutional Review Board
• http://www.ich.org/cache/compo/276-254-1.html
• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrs
earch.cfm