good clinical practice (gcp)
DESCRIPTION
GOOD CLINICAL PRACTICE (GCP). Dr. Ofri Mosenzon Clinical research Unit Diabetes Unit, Internal Medicine, Hadassah University Hospital, Ein Kerem. GOOD CLINICAL PRACTICE (GCP). ืืื ืืืืช ืืื?? ืืื ืืืืช ืื ืืื ืืงืืื ื?? ืืื ืืคืจืงืืืงื ืืืงืืืืช?? - PowerPoint PPT PresentationTRANSCRIPT
GOOD CLINICAL PRACTICE (GCP)
Dr. Ofri Mosenzon Clinical research Unit
Diabetes Unit,Internal Medicine,
Hadassah University Hospital, Ein Kerem
GOOD CLINICAL PRACTICE (GCP)
โข?? ืืื ืืืืช ืืืโข?? ืืงืืื ื ืื ืืื ืืืืช ืืืโข?? ืืืงืืืืช ืืคืจืงืืืงื ืืื
(not always good, usually not clinical practice )
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
Good Clinical Practice- Definition
An international ethical and scientific quality standard for:โข Designing, โข Conducting,โข Monitoring/Auditing, โข Recording,โข Reporting
trials that involve the participation of human subjects.
- ื ืื ืืืืช ืืื ืืืืื ืืืืงืจ ืืฉืืื ืืืื ?GCPืืืื
)1. ืืืืงืจ ืคืจืืืืงืื ืืชืืืช)2 : ืืืืื ) ืืื ืืืืื ืืืื ืืืืืื ืืืืจืช ืืืืจืช
inclusion /exclusion criteria.) )3. ืืจืืฉื ืืืืงืจ ืืืื ืืืืื ืืื ืืืืืื ืืืืื)4. ืืืืืื ืืื ืืืืงืืช ื ืืืืช)5. ืืืืงืจ ืกืืื ืืืืจ ืืืืืข ืฉืืืจืช)6 . " ื ืืื ืืื ืืฃ
Good Clinical Practice- Is not directly involved with:
โข The good clinical care a doctor needs to give his/her patient
โข The underlying doctor-patient relationship
GCP is one of my best teachers!!
What is the purpose of GCP?
โข To protect participants involved in trials:
Compliance with GCP provides public assurance that the rights, safety and well being of trial subjects are protected.
โข To ensure the credibility of the data generated in the trial.
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
GCP-History
โข 2nd World War- Nazi's โmedical experimentโโข 1946 Nuremberg Code
โข First internationally recognized code of medical research, standard of integrity, guide, no law
โข 10 fundamental ethical principles, most significant and lasting:
โข โ The voluntary consent of the human subject is absolutely essentialโ )Basis of Informed Consent(
GCP-Historyโข 1961 Thalidomide Tragedy
โข No means of recalling
dangerous investigational drugs.โข Poorly controlled dissemination of investigational drugs to physicians.
โข Investigational nature of drugs unknown to patients.
โข Inadequate records on the use of investigational drugs.
GCP-History
โข 1962 Kefauver -Harris Amendmentsโข Required submittal of an Investigational New Drug Application (IND)
โข Required substantial evidence of Efficacy โข Required pharmaceutical companies to register with FDA
โข Established role of FDA in regulatory/ research process
GCP-History
โข 1964 Declaration of Helsinki โข )amended in 1975, 1983, 1989, 1996, 2000, 2001and 2008(.
โข Set of ethical principles regarding human experimentation developed for the medical community by the World Medical Association
โข A foundation of modern clinical trial ethics โข Not accepted universally as a whole โข Not legally binding
GCP-History
โข 1979 Belmont Reportโข Abuse associated with Tuskegee Syphilis study
โข Three basic principles:โข 1. Respect for personsโข 2. Beneficenceโข 3. Justice
)Basis of IRB:
Institutional Review Board(
GCP-History: INITIATION OF ICH
โข ICH:
โข International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use
GCP-History: ICHโข ICH was organized to reduce differences in the technical
procedures involved in pharmaceutical development conducted in various countries
โข ICH E6 Good Clinical Practice Consolidated Guidance resulted from the meetings.
โข Participants included regulatory officials and pharmaceutical specialists from:
โข European Union โข Japan โข United Statesโข
ICH/GCP
โขFocus on 3 main areas:
1. Safety
2. Efficacy
3. Quality
ICH/GCPโข It is a standard most widely agreed upon โข It is the law: โข Directive 2005/28/EC of 8 April 2005 of the European
Parliament and of the Council โข National regulations of most countries. โข FDA regulations, i.e.:โข ICH Guidance adopted by FDA )E6, GCP: Consolidated
Guideline, www.ich.org( โข โช21 CFR 312: IND โข โช21 CFR 50: Informed Consent โข โช21 CFR 54: Financial Disclosure โข โช21 CFR 56: IRB
- ื ืขืืกืง ืืื ืืขืืงืจืืื ืืชืืืืื ืื ?ICHืื
)1. ืืจืืคืืื ืืชืจืืคืืช ืืืจืืช ืืื ืืงืฉืจ)2. ืื ืืืงืืช ืืชืจืืคืืช ืืขืืืืช)3. ืืงืืืื ืืืืืื ืืืืคืื ืืืืืช)4. ืื ืืืงืืช ืืชืจืืคืืช ืืืืืืช)5. ืืืืงืจืื ืืืฆืืข ืืืืืช)61+2+3)72+4+5)83+4+5)9. " ื ืื ืื
GCP-History: Israel
โข Until 1978, Clinical Trials were performed without legal framework
โข 1978, Department of Pharmacy, Ministry of Health )MOH( took on responsibility for Clinical Trials
โข 1980 Peopleโs Health Regulations
)ืชืงื ืืช ืืจืืืืช ืืขื ืืชืฉืโื(โข http://www.health.gov.il
GCP-History: Israel
โข Helsinki Approval: โข 1993 The Department for Medical Devices )ืื"ืจ(
โข 1996 Incorporation of ICH GCP into National Regulations
โข In case of disagreement between the different regulation: National )MOH( regulations prevail
How does working in accordance with ICH/GCP help ?
โข Single standard of practice โข Provides universally accepted data โข Ensures subjects are informed and protected โข Economical โ do it right, do it once โข Assures your work and reputation as being scientifically sound, with high ethical and scientific standards
- ืืื ืืืืช, ืืื ืืกืืื ืืืกืจ ืงืืืืช ืื ืืืฉืจืื? ืืงืืืขืช ืืื ืืื ืืื ืื
)1- ื FDAืื ืืืืช
)2- ื EMAืื ืืืืช
ืืืจืืืืช 3( ืืฉืจื ืื ืืืืช)4- ื GCPืื ืืืืช
)5 - ื .ICHืื ืืืืช
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
Roles and responsibility in clinical studies
โขWeโre all in this together: IRB/EC, Investigator, Sponsor, FDA/ other regulatory agencies
โ Providing public assurance that the rights, safety, and well-being of subjects are protected
โ Ensuring clinical data are reliableโ Developing important new therapies for the public
โข But the responsibility of each one should be clearly defined.
IRB/EC responsibilities
Initial and continuing review and approval of: โขClinical protocol โขProtocol amendments โขConsent form โขAll materials for study subjectsโข All safety and progression reports
IRB/EC
โข No start of a clinical trial without EC approval (and regulatory authority)
โข Approval of all information designated for trial subjects
โข Approval of any substantial amendments before implementation
โข Expedited and regular safety/status reports to EC (and authorities)
ืื ืืกืื ืืงืฉื ืืืืฉืช ืืกืืืื ืงืืืฅืฉืื ืื- ืกืืืื ืจืคืืื
ืืชืืฉืืจ. ืจืคืืื ื ืืกืื ืืจืคืืื. / ืืืฉืืจ ืืืืืืจ ืจืคืืื ื ืืกืื ื
ืืืื. ืืจืงืืืช ืชืืื ืืืืื ืืืืฆืจ ืจืคืืื ื ืืกืื ื) ืืืื ื ) ืื ืืฉื ืืืงืืจ
ืื ืื. ืจืคืืื ื ืืกืื ืืืืงืจ. ืืืฆืจ ืืื ืจืคืืื ื ืืกืื ื
ืืืืฉืช ืืืกืืืื ืืืืืืช ืืืื ืืืจืคืืื ืื ืืกืื ืืงืฉื
1. : ืืงืฉื , ืืืคืก , ืืชืืืืช ืืฃ ืืืืจืื ืืจืืคื ืืฆืืจืช ืื ืืกืื ืชืืฆืืช
ืืืืืจืื. 2 ืืืขืช ืืกืืื ืืืคืก3 / / ืืื. ืคืกืืื ืืกืืืื ืืงืืื ืื ืืืขืช ืืกืืื ืืืคืก4 : ืืืืื. ืืชืืืืืืช , ืืืคืก , ืืืฉื , ืืจืืืื ืืืจืืขืื ืขื ืืืื ืืืืื ื ืืืืจ
- ื ืืืงืจ ืืืฆืจ ืฉื ืื 3ืืชืืืืืื. 5 ืืฆืืจืช ืืืคืกืืกืืืื. 9 ืจืฉืืืช
ืืฉืชืชืคืื. 10 ืืืืก ืืืืขืช ื ืืกืืืืืืื. 11 ืืงืืคืช ืืืืคื ืืจืืคื ืืืชื
ืืืง ) (2004ืืืกืืจืื , ืืคื
ืืงืฉื ืืืืฉืช ื ืืกืคืื ืืฉืืืื ืืกืืืืืจืคืืื ืื ืืกืื
ืื ืืกืื โข ืคืจืืืืงืืืืืืงืจ )โข ืืืืฆืจ ืืืืงื ืืืืงืจ (IBืืืืจืชืจืืืื ืืืช โข ืชืืืืช ืกืคืจืืช
? / ืืืชืืงื ืืืขืืช ืืช ืืืืข ืืืืืฉ ืฆืจืื ืื ืื
ืืืืคืก 1( ืฉืื ืื ืืฆืจืื ืฉืืื ื ืืคืจืืืืงืื ืงืื ืฉืื ืืืืืกืืื.
ืืืจืืื ื 2( ืืกืืื ืชืืจืืชื ืืืืงืจ ืฉืืืืกื ื ืื ืขื ืืืืืืืืงืื 53 .50ืืืืื ืืืืื
ืืชืจืืคื 3( ืขื ืืืืืช ืื ืืกืืืื ืฉื ืืฆื ืืืฉ ืืืืขืื ืืืงืช.
ืืชืจืืคื 4( ื ืฉืืืช ืืฆืืจื ืืืืืื ืชืืงืื ืฉื ืืืืงืืืืืชื.
)5 " ืืชืืืช" ืืชืื ื ืื ืฉืื ื ืืืืงืจ ืขื ืคืจืกืื ืืืืขืช. ื" ืืืื
)6. " ืืืืื ืืฉ ื ืื ืื ืืช
Approval of clinical study in Israel
โข Special Clinical Trial: EC / Hospital Manager can approve
โข Other Clinical Trial: requires EC and Ministry of Health approval
What is a special clinical trial? ื ืืกืื ืจืคืืื ืืขืืฉื ืฉืืืืฉ ืืชืืฉืืจ ืจืคืืื ืืจืฉืื โข
ืืืฉืจืื, ืื ืืืชืจ ืืฉืืืืง ืืืจืฆืืช ืืืืจืืช )ืืขืจื ืืืจืืคื, ืืจื"ื, ืืคื(,
ืืืชืืืื ืืจืฉืืื, ืืฆืืจืช ืืืชื ืืืืื ืื ืืืงืืื.ืื ืืกืื ืืจืคืืื ืืื ื ืืชืืื ื ืืืืขืจื ืืืืืืืกืืื ืืืืืืช โข
)ืงืืื ืื ืืืกืจื ืืฉืข(
IVืืืืืื : ืืืงืจ ืืฉืื โข
" ืืืืื " ืืืงืจ ืืื ืืืืืงืจืื ืืืื
ืืื ื 1( ืืืืืืจืื ืืืืืฉืจืช ืชืจืืคื ืืชื ืืืืืง .16-18ืืืงืจ)2 " ืืคืืืขื ืืืคืื ืืฆืืจื ื ืื ืืืืคืื ืืืืืฉืจืช ืชืจืืคื ืืชื
. ืกืืืจืช ืจืงืข ืขื ืืืืืชื)3. ืืืื ืฉื ืฉืื ืืช ืืฉืขืืช ืืืืฉืจืช ืชืจืืคื ืืชืืงืื 4( ืืืจืื ืืืืฆืืืืืจ ืืืืคืื ืืืืฉืจืช ืชืจืืคื ืืชื
. ืงืฉื ืืืจืื ืืืฆืืืืืจ ืขื ืืืืช ืืืชื ืืืืฉืคืืื ืืืืืื
Investigator "A person responsible for the conduct of the clinical trial at a clinical trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.โ
DEFINITION - INVESTIGATOR
ICH-GCP 1.34
Investigatorโs Responsibilities(Source: ICH GCP / FDA)
โข USA:FDA 1572 Form: legally binding agreement between Investigator and Sponsor
โข Israel: ื1ื, 1ื ืกืคื
โข Protocolโข Investigatorโs Brochure )IB(โข Informed Consent )ICF(โข Sponsorโs undertaking )No 4(โข Investigator Checklist )No 9(
Investigatorโs Qualification and Agreements
โข Investigator:โข Qualified, trained experienced in the field of the trial research
โข Meet regulatory requirements, submit updated CV and relevant documentation to Sponsor / regulatory authorities, GCP trained.
โข Familiar with investigational product, protocol and IB )Investigatorโs Brochure(
Investigatorโs responsibilities-1(Source: ICH GCP)
โข Ensuring the investigation is conducted according to signed agreements, protocol, and applicable regulations
โข Exception: to eliminate an apparent immediate hazard to subject
โข Protecting the rights, safety, and welfare of subjects under investigatorโs care
Investigatorโs responsibilities-2(Source: ICH GCP)
โข Maintain adequate and proper records
โข Collection of Data:
1. Source documentation: The source is the first
capture of data )i.e., ECG, clinic notes, hospital
records, patient diaries, lab reports(
1. Clinical Report Forms (CRF) )electronic CRF-
eCRF(
Maintenance of Study Records
โข Study records should be retained for 2 years post FDA approval of the last marketing indication or 15 years after end of trial.
โข Study records should be securely stored and be easily retrievable for sponsor audits and regulatory inspections
Investigatorโs responsibilities(Source: ICH GCP)
โข All reports and connection with the IRB/ECโข Responsible for accountability of investigational product
โข Provide adequate resources )time, staff, facilities(
PI - Principal Investigator
Sub-investigators
Clinical Research Coordinator )CRC(
Others
CREATING A STUDY TEAM
Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective
task(s).
ืืฉืจื ื ืืื ืืคื ืืืืงืจ ืืืืืืืจืืืืช?
/ ืจืืฉื ืืืงืจ ืืืฉืืฉ" : ืืืงืจ ืฉืื ืืื ืจืืคื ืื ืืืจืฉื ืจืืคืืืคืจืืืืงืื ืืืืืืจ ืืจืคืืื ืื ืืกืื ืืขืจืืืช ืืืจืื ืืืงืจ
ืื ืืกืื"(10, ืืืืจืืช, ืกืขืืฃ 2006)ื ืืื ืื ืืกืืืื ืจืคืืืืื ืืื ื ืืื
:ืื ืืื ืืฆืืืช ืื ืืกืื ืืจืคืืื, ืฉืืื ื ืขื ืืื ืืืงืจ ืืฉื ื" ืืืืงืจ ืืจืืฉื ืื ืืฆื ืืืฉืืืชื, ืืืชืจ ืื ืืกืื, ืืืืฆืืข ืืืืืื
ืงืจืืืืื ืืงืฉืืจืื ืื ืืกืื ื/ืื ืืงืืืช ืืืืืืช ืืฉืืืืช ืืงืฉืืจืืช ืื ืืกืื"
(11, ืืืืจืืช, ืกืขืืฃ 2006)ื ืืื ืื ืืกืืืื ืจืคืืืืื ืืื ื ืืื
? ืืืจืื ืื ืืจืืฉื ืืืืงืจ ืืื
ืืืืขืื 1( ืืจืืฉืื ืืื ืืืืงืจ ืืกืืื ืืืืฉืชืืืชืืช.
)2. ืืืชืืช ืืืืขืื ืชืงืืคืชืืื ืืืืืืช ืืืืืื ืืืืฉืช)3. ืืืจืงืืช ืืืืช ืืืืงืจ ืชืจืืคืืช ืืืืขืชืชืจืืคืืช 4( ืฉื ื ืืื ื ืืืคืจืืืจื ืขื ืืฉืืืจื
. " ื ืืื ืฉื ืืืจืงืืช ืืืืช ืืืืงืจืืชืืืช 5( ืืืื ืขื ืื ืืื ื ืืชืจืืคื ืฉื ืืื ืคืงื
. ืืืืื ืืืืงืจ)6. ืืืชื ืืขืืื ืืืฉื ื ืืืงืจ ืฉื ืืขืืืื
Sponsorโs Responsibilities
โข Responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure trial conduct and data generated, documented and reported in compliance with protocol GCP and regulatory requirements
โข Document financial aspects in an agreement between sponsor and investigator / institution
Monitoring (ICH GCP)
PURPOSE:โข Protection of rights and well-being of
human subjectsโข Conduct of trial in compliance with
Protocol, GCP, applicable Regulatory Regulations
โข Done by: Clinical Research Associate )CRA( hired by the sponsor directly, or through a Clinical Research Organization )CRO(.
Sponsor responsibility- Quality Control
โข Check all Study recordsโข Informed consent forms )related procedure(โข Laboratory reportsโข Subject Hospital charts / Physiciansโ notesโข Original recordings from instruments e.g.. EKGs, x-raysโข A list of the trial staff involved with the studyโข Drug accountability recordsโข CRFs and data clarification formsโข Laboratory reference ranges and accreditationโข Equipment calibration/validation records
What is an Audit?
โขAn independent examination of trial related activities and documents
Purpose of Audits
โข Review adherence to appropriate Regulations, Good Clinical Practice, SPONSOR Protocols
โข Provide independent feedback to SPONSOR management on the clinical trial conduct
โข Identify and address issues in advance of possible regulatory inspection
โข Assess and share how both SPONSOR and
investigators can improve performance
On-site Auditโข Review of:
โข Study documentationโข Informed Consent Forms and
consent processโข CRFs and subject records
โข The site facilities including drug
storage
โข Exit meeting to discuss audit
observations
Top 5 Audit Findings for Investigators
โข Failure to follow the protocol
โข Failure to keep adequate records
โข Failure to account for disposition of IP
โข Problems with the ICF and/or process
โข Failure to report AEs or changes to
appropriate parties
Criminal Investigations )not in Israel(
- ืืืงืืจืช ืืืฆืข ืืืื ืื ?AUDITืื
)1. ืืืืงืจ/ ืืช ืฉืืืฆืขืช ืืืืจื ืืืืื)2. ืืืืกืืืช ืืืชืืงื ืืืขืืช)3. ืืืจืืืืช ืืฉืจื)4FDA/EMA
)5- ื . CROืืืจืช ืืืืื ืืืื ืขื ืฉื ืฉืืจื)6 " ืืืฆืข ืืืืืื ื ืื AUDITืื
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
Obtaining Informed Consent
โขNot just the signature of a document โข Interactive process โขOpportunity for questions โขTime to make decision โขNo undue influence
Obtaining Informed Consent
โข Complete explanation include: โข Investigational drug: what is known and what is not known, other treatments available, etc.
โข Benefits/risks โข Confidentiality of recordsโข Requirements from the patients
โข Sign/date consent prior to any study procedure โข Process must be documented in source
ืืืืื - ืืืืืืช ืืืง ืืืขืช ืืืกืืื ื ืืื
โข , ืืืืื" ืขื ืืฉืืืจ ืืืืืืื ืืืคื ืขื ืืื ืฉื ืืืืืชื, , ืืกืื ืขืงืจืื ืืช ืืื ื ืืฉืจ ืืืืจืืชื ืืืืืืชืื
ืืฆืืจืช โข ืืจืื ืืื ืืื ื ืจืคืืืืื ื ืืกืืืื ืืขืจืื ืืืืืื ืืื"... ื ืืืชืื ืงืืื ืืื ืืืืืืื ืืืืชืื ืืืกืื ืงื
โข , ืืกืืื , ืืืืื ืืงืื ืืืืื ืืฉืืจ ืืืืคื ืืื ื ืืืจืชืืจืืืช ) ืืืืจืืืืชื ืืืืคื ืืงืฉืืจื ืคืขืืื ืืื ืืืขืช
) ืืื ื, ืฉื ืืืื ืื ืืืืืืืช ืจืงืืืช ืืืืจืื
( " ื ืืชืฉื ืืืืื ืืืืืืช ( 1996ืืืง ืืืกืื ืงื (, ) ืืฆืืจืช ื ืืกื ืืขื ืืจืืืืช ืชืงื ืืชืืืฉืชืชืฃืืืืข ืืืืงืจืืืชื ืืืืช ืืช ืืคืจื ืืืจืืืืช ื ืืกืืืืืงืืื ืืืืืืฉืจื ืื ืืื
ืืจืคืืื ืื ืืกืื ืขื
ืงืืื" โข ืื ืืื ืืื ืื ื ืื ืืืขืืจืืื ืจืคืืื ื ืืกืื ืืืขืจื ืื , ืืจืคืืื ืื ืืกืื ืืืฉืชืชืฃ ืืื ืฉื ืืืขืช ืืกืืืชื ืืช ืืืืงืจ
ืืชืืื ืืืืืื ืืกืืจ ืื ืืกืื ืืืฉืชืชืฃ ื ืชื ืฉืืืืงืจ ืืืืจ" ืืจืคืืื ืื ืืกืื ืืืขืช ืืืกืืื ืืืคืก ืืช ืงืจื ืืืืฉืชืชืฃ
ืืกืืื" โข ืืืคืก ืืื ืขื ืืืชื ืชืื ืชื ืื ืืกืื ืืืฉืชืชืคืืช ืืกืืื" " ื ืืกืื, ืืืืชื ืืืกืื ืงื ืืืขืืช ื ืข ืฉืืืฉืจ ืืืขืช
ืืื" โข ืขื ืืื ืืืฉืชืชืฃ ืืื ืขื ืื ืืืืชื ืืืขืช ืืกืืื ืืืคืกืืืืงืจ"
โข" ืืืฉืชืชืฃ" ืืืื ืืืืกืจ ืืืชืื ืืืกืืื ืืืคืก ืฉื ืืขืชืง
: ืืืืื ืืืื ืืจืืคื ืืื ืืชืงืฉืจืืช ืืืื ืืืกืืื ืืืคืก
ืืืืืืช โข ืืฉืืืจืช ืืงืืื ื ืืืืงืจ ืฉื ืืืื ืื ืืื ื ืืืกืืื ืชืืืื) ืจืืืืฆืื ) / / ืืืง ืืชืืงื ืืืฉืชืชืฃ
ืืืกืืื โข ืฉืืืืคืก ืืฉืื ืืืื ืขื ืืขืชื ืืืชืช ืืงืื ืืืืื ืืืืงืจืื โข ืืช ืืืืืช ืืืื ืขื ืืืืชืืื ืฉืื ืืกืื ืืื ืืืกืืื ืืืคืก
ืื ืืงืืืืื ืืกืขืืคืืืืกืืืืื โข ืกืขืืคืื ืืืืื ืื ืืืืืง ื ืืชื ืืืืจืืฉื โข ืืืืงืจ ืืืืจืืืช ืืื ื ืืืกืืื ืืืคืกืืืืฉืจ โข ืืืกืืื ืืืคืก ืขื ืืขืืืจ ืืืืืื ืืืืืช ืืช ืืฉ ืืืืงืจ
ืืืชืืืืืจื โข ืืืฉืื ืืจืคืืื ืื ืืกืื ืขื ืืืืข ืืืฉืชืชืฃ ืืืชื ืืืืงืจ ืืืืช
ืืืื ืช ืืืฉืคื
ืืืื ืื ืืกืื ืขื ืืืืข
ืืืืื โข ืฉื ืืืืงืจื ืืืืคื ืขื ืืกืืจืืืืงืจ โข ืืืจืชืืืฉืชืชืคืืช โข ืชืงืืคืช ืืฉืืืฉืื ืื โข ืืืืืืื ืชืืืจโข) ืคืืฆืื ) ืืจืืืช ืืืืงืจ ืืืจืืขืืช ืืืช ืืื ืืืืืื ืืกืืืื ืฆืืืืืฆืคืืืื โข ืืืชืจืื ืืช ืชืืืืจืืืคืฉืจืืื / โข ื ืืืืช ืื ืืกืืืื ืื ืชืืืืจืืืืคืืื โข ืืืคืืืื ืขื ืืกืืจืืืืงืจ โข ืืืกืืจืช ืฉืืืกืคื ืื ืชืื ืื ืืืกืืื ืืืื ืืฆืืจืืืืืื โข ืฉืืืจืข ืืืื ืขืช ืืื ืืืืกืืื ืืกืืช ืืคืฉืจืืช ืืชื
ืืืืืคืื
ืืืขืช ืืกืืื ืืืืฉื ืืฉืืขืืช ?ืื
ืืืืืข โข ืื ืืช ืงืืื ืืืืื ืื ืืืืื ืืืืคื ืขืืืืฉืืืช ืืืืื ืืงืื ืื ืช ืขื ืื ืืืจืืฉ ืืจืคืืื
ืื ืฉืืืฆืข ืืืืคืื ืืืืจโข : ืื ืฉืฆืคืื ืืจืคืืื ืืืืื ืืช ืืืื ืืืืื ืืืืืคื ืขื
, ืืงืืืืืช, ืืืืืืจื ืืืืืช ืกืืืื ืื ืชืืขืืชื ืืฉืืืืชืื ืืืืคืื
ืืืงืืืช - ืืืขืช ืืกืืื
ืืืชื โข ืืืืืคื ืฉื ืืืขืช ืืกืืื ืืงืื ืืืคื ืฉื ืืืืชื . ืจืคืืื ืืืคืื
โข ) ืืืืื ) ืื ืืชื ืืคืงืืืืช ืืืงืื ืจืืฉืืช ืืืงืืงื ืืืืกืกืช ืื ืืืื . ) ืืืืื ) ืืืืืืช ืืืืง ืืชืงื ืืช ืฆืืืื ืืฉื ื ืืืงืืงืช ืื ืขืืื
Informed Consent-Summaryโข Forms must be approved by ethics committeeโข Patient must sign prior to any study procedures being
performedโข A signed copy of the ICF must be given to the patientโข The ICF process must be documented in each patientโs
source document/patient chartโข Informed consent was freely given and reviewed with the subjectโข The subject was given ample time and opportunity to inquire about details of
the trialโข Prior to participating in the trial, the written ICF was signed and personally
dated by the subject and by the person who conducted the informed consent discussion
โข A copy of the signed informed consent form was given to the subject
ืืืกืืื ืืืคืก ืขื ืขื ืืืชืื ืืืืื ืืืงืจืื ืืืืื? ืขืฆืื ืื ืืืง ืืืงืื
ืื 1( .16ื ืขืจ)2. ืืืืฃ ืืืงื ืืคืืืจืืคืืก ืื ืฉืืฉ ืืื)3. ืขืืืจืืช ืงืืจื ืื ืืืืจ ืฉืื ืืืืขืืืืจ.4(ืื ืืืคืืช.5(
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
Adverse events (AEs)- Definition
โข Any adverse change from the patientโs baseline (pretreatment) condition that occurs during the course of the clinical study after the patients has started therapy, whether considered drug related or not.
โข Any diagnosis, syndrome, symptom or lab abnormality that is a new finding (not documented in the patientโs history).
โข Any pre-existing condition that has worsened or recurred during the study.
Adverse events (AEs)โข All AE must be reported to sponsor.
โข All AE reports should include:
1. Start date and time
2. Severity: mild, moderate, severe.
3. Investigator judgment of relation to study drug: possible, probable, etc.
4. Result: recovered, continue, death etc.
5. Stop date and time.
Adverse events (AEs)- Definition-Cont.
โข AEโs โ Adverse eventsโข SAEโs โ Serious adverse eventsโข SUSARโs โ Serious Unexpected Severe Adverse Reaction )s(
Serious adverse events
Any adverse event that meets one or more of the following Regulatory requirements:
1. Death
2. Life-threatening )immediately(
3. Inpatient hospitalization, or prolonged hospitalization
4. Persistent or significant disability/incapacity
5. Congenital anomaly/birth defect
6. Important medical event
ืฉื SAEืื ืืืืืจื ?Severeืืืื ืืื1(ื ืืื 2( ืื
ืฉื AEืื ืืืืืจื ืืื Severeืฉืืื?SAEืืืืจื
ื ืืื3(ื ืืื 4( ืื
Expected adverse events
โข Events that are specifically mentioned in the investigatorโs brochure as being possible side effects
โข Unexpected adverse eventsโข adverse events which have not been described in
the current investigatorโs brochure or package insert before with this drug
โข If occur, must be reported to Authorities
Non-listed events
โข hospitalizations for pre-existing/non-worsening conditions
โข elective proceduresโข diagnostic proceduresโข baseline discoveriesโข laboratory abnormalitiesโข events occurring after tracking time
Lecture Plan:
โข Definition and purpose of GCP
โข A little bit of history- world wide and in Israel
โข Roles and responsibility: investigator, sponsor, ethic
committee
โข Informed Consent=IC
โข Adverse Events=AE
โข Conclusion
ืืื ) ืืืืช ืืื ื ืจืคืืื ืืืืงืจ (1ืืืฉืชืชืฃ
ืืืืงืจ โข ืืืฉืชืชืฃ ืฉื ืืืืืชื ืืืืื ืืืืงืจ ืืจืืคืืืืืจื โข ืืืืช ืืจืืืช ืืืจ ืื ืืข ืืื ืงืืืืช ืืืืืคื ืืืืช
ืืืืข ืืืืืฉืชืชืฃ โข ืฉื ืืืืืืืชื ืืจืืืืชื ืขื ืืืื ืืืจืื ืืืืงืจ
ืืกืืืชื ื ืชื ืื ืื ืืืืงืจืืกืืืื โข ืขื ืืืืจืช ืืืืงืจ ืืชืืขืืช ืื ืืืืื ืืืืงืจ
ืืืฉืืขืจ ืฉืื / / โข ืืื ื ืืง ืกืืืื ืืฉืืคื ืืืืขืจ ืขืืื
ืืื ) ืืืืช ืืื ื ืจืคืืื ืืืืงืจ (2ืืืฉืชืชืฃ
ืืืืจื โข ืืืืื ืืืฉืชืชืฃ ืืฉืชืชืคืืช ืืช ืืคืกืืง ืืืืงืจื ืืง
ืจืืืฉื โข ืืืืืืืกืื ืืืงืจ ืืืืฆืืข ืืืื ืข ืืืืงืจืืจืืชื ืชืืช ืื ืืฆืืช
ืืื โข ืืืืฉืจ ืื ืจืง ืืื ืืื ื ื ืืกืื ืืขืจืื ืืืืงืจืืืืชืืืืืืืื ืืืชืืงื ืืืื ืืช ืฉืืื ืืืืืจ
ืืืืงืจ ืืืืฆืืข ืืงืฉืืจืืืืื โข ืืืฉืชืชืฃ ืขื ืกืืืจ ืื ืืืฅ ืืืคืขืืช ืืืื ืข ืืืืงืจ
ืจืืื ืืื ืื ืืืืคืื ืืืืืช ืืช ืืืฉืชืชืคืืช ืืชื ื
โข(," ืจืคืืืืช " ืืชืืงื ืืกืคืจ , ืืชืื ืจืืก' ืืืื ืืขื (2010ืคืจืืค
ืืืืื ื ืขื ืชืืื[email protected]