Good Clinical Practice
Overview Of Good Clinical Practice
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 Studies initiated & continued only if anticipated benefits outweigh risks Rights, safety & welfare of human subjects take priority over interests of science & society Available non-clinical & clinical info on product adequate to support study
2. 3. 4.
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 subjects 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 cant 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 Subjects 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 subjects willingness to participate in study Contact info for questions re: subject rights; trialrelated adverse events Circumstances under which subjects participation may be terminated
Investigator Brochure What It Is
A compilation of clinical & non-clinical data on the product that is relevant to the products 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
