TRAINING 7-2010 Good Clinical Practice

8/9/2019 TRAINING 7-2010 Good Clinical Practice

1/32


2/32

Agenday History

y ICH E6

y Good Clinical Practice

y FDA Guidelines

y References

2Confidential, 7/19/2010


3/32

THE NUREMBERG CODEy In 1947 the War Crimes Tribunal meeting at Nuremberg

convicted 23 German defendants, most of whom were

physicians, of performing criminal experiments onhuman subjects. The Tribunal propounded ten

standards to guide physicians in carrying out

experiments on human subjects in the future.

y Resulted in the requirement of Informed Consent,among other requirements



4/32

Declaration of Helsinki - 1964y The World Medical Association (WMA) has developed

the Declaration of Helsinki as a statement of ethical

principles for medical research involving humansubjects, including research on identifiable human

material and data.

y Wide adoption of the principles set forth in the

Nuremberg Code.



5/32

Declaration of HelsinkiWORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI

Ethical Principles for Medical Research Involving Human Subjects

y Adopted by the18th WMA General Assembly Helsinki, Finland,

June 1964

y and amended by the

y 29th WMA General Assembly, Tokyo, Japan, October 1975

y 35th WMA General Assembly, Venice, Italy, October 1983

y

41st WMA General Assembly, Hong Kong, September 1989y 48th WMA General Assembly, Somerset West, Republic of

South Africa, October 1996

y 52nd WMA General Assembly, Edinburgh, Scotland, October

2000



6/32

The Belmont Report - 1979y Ethical Principles and Guidelines for the protection of Human

Subjects of Research (The National Commission for the Protection

of Human Subjects of Biomedical and Behavioral Research)

y Three basic ethical principles, applied through:

y Informed Consent

y Systematic assessment of Risks and Benefits

y Fair procedures and outcomes in selection of subjects



7/32

Good Clinical Practice: ICH E6 (1996)

y Good Clinical Practice Guideline (ICH E6) includes protection of

human rights for subjects in clinical trial.

y

It also provides assurance of the safety and efficacy of the newlydeveloped compounds or medical devices (includes IVDs).

y Good Clinical Practice Guidelines include standards on how

clinical trials should be conducted, define the roles and

responsibilities of clinical trial sponsors, clinical research

investigators, and monitors (clinical research associates).



8/32

ICH GCP E6 - Sectionsy IRB/Ethics Committee

y Investigator

y

Sponsory Clinical Trial Protocol

y Investigators Brochure

y Essential Documents for the Conduct of a Clinical Trial



9/32

Principles of ICH E6 GCPy Clinical trials should be conducted in accordance with the ethical

principles that have their origin in the Declaration of Helsinki.

y Risks should be weighed against potential benefits.

y Rights, safety and well being of the trial subjects are the most

important considerations.

y Available clinical and nonclinical information on the investigational

product should be adequate to support the clinical trial.

y Clinical trials should be scientifically sound and described in a

clear, detailed protocol



10/32

Principles of ICH E6 GCPy The trial should be conducted in compliance with a protocol that

has received prior institutional review board (IRB) approval.

y

The medical care and medical decisions made on behalf ofsubjects should always be the responsibility of a qualified

physician.

y Each individual involved in conducting a trial should be qualified

by education, training and experience.

y

Freely given informed consent should be obtained from everysubject prior to participation in a clinical trial.



11/32

Principles of ICH E6 GCPy All clinical trial information should be recorded, handled and

stored in a way that allows accurate reporting, interpretation and

verification

y The confidentiality of records that could identify subjects should

be protected. Confidentiality must be maintained according to

applicable regulations.

y Investigational product should be manufactured, handled and

stored according to good manufacturing practice (GMP) and used

according to the approved protocol.

y Systems with procedures that assure the quality of the trial should

be implemented (SOPs).



12/32

IRB Responsibilitiesy To safeguard the rights, safety and well-being of all trial subjects



13/32

Investigator Responsibilitesy Qualified by education, training and experience

y Familiar with appropriate use of the investigational product

y Aware of and able to comply with GCP

y Have adequate resources to complete the trial

y Provide appropriate medical care for trial subjects

y Run the trial with IRB/EC approval. This includes informed consent of trial

subjects

y

Comply with the protocol, including appropriate subject enrollment, accuratedata entry, and reporting of deviations and adverse events

y Have source documentation available for monitoring and audits as needed

y Submit a final report to the Sponsor and IRB at the conclusion of the trial



14/32

Sponsor Responsibilitiesy QA/QC

y Implement and maintain written SOPs.

y Secure written agreements from all involved parties to ensuredirect access to all trial-related source data, documents and

reports for monitoring and audits.

y Apply QC to each stage of data handling to ensure data

integrity.



15/32

Sponsor Responsibilityy Medical Expertise

y Designate appropriately qualified medical personnel to advise

on trial-related medical questions or problems.

y Trial Design

y Utilize qualified personnel as appropriate through all stages of

the trial process (protocol and CRF design, analyses planning,

interim and final reports).



16/32

Sponsor Responsibilityy Trial Management/Data Handling/Recordkeeping

y Utilize appropriately qualified individuals to supervise

y Overall conduct

y Handle data

y Verify data

y Conduct statistical analyses

y Prepare trial reports

y If using electronic data capture, ensure the system isvalidated and SOPs are in place.



17/32

Investigator Selectiony Investigators qualified by training and experience

y Must have adequate resources

y Must agree to conduct the trial according to GCP

y Must agree to comply with the protocol, data reporting

y Must agree to permit monitoring, auditing

y Must agree to retain essential documents

y Should sign the protocol (or alternate document) to confirm

agreement



18/32

Confirmation of review by IRBy Sponsor must obtain from the investigator

y Name/address of the institutions IRB

y Documented approval of IRB approval of the protocol, current

informed consent and any other written information provided

to the subjects

y If any modifications are made to the protocol, updated

approvals from the IRB must be obtained.



19/32

Investigational Producty Investigational product must be manufactured, packaged and

labeled according to applicable GMP.

y Sufficient safety and efficacy data must be available to support the

current clinical trial.

y The sponsor is responsible for maintaining records documenting

shipment, receipt, disposition, return and destruction of

investigational product.



20/32

Monitoringy Monitoring ensures:

y The rights and well-being of subjects are protected

y Reported trial data are accurate, complete and verifiable

y Conduct of the trial is in compliance with the currently

approved protocol, and in compliance with GCP

y Sponsor is responsible for ensuring the trial is adequately

monitored



21/32

Monitorsy Monitors should be appropriately trained

y Scientific and/or clinical knowledge to monitor the trial

adequately.

y A monitors qualifications should be documented

y Monitors should be familiar with the product, protocol,

informed consent, SOPs, GCP



22/32

Monitorsy Monitors responsibilities

y Ensure and verify proper conduct and documentation of the

trial

y Verify investigator qualifications and resources

y Verify proper informed consent procedures

y Ensure all site personnel are informed about the trial and

any updates

y Verify data entry on CRFs is consistent with source

documentation

y Verify that adverse events are reported in accordance with

the protocol and within time periods required by GCP

y Verify that the investigator is maintaining the essential

documents



23/32

Monitoring Reporty There should be an established monitoring SOP

y Monitoring reports should be completed after each monitoring visit

y

Date, site, name of monitor, site personnel visitedy Summary of what was reviewed, significant findings,

deviations and deficiencies, actions to be taken to secure

compliance



24/32

Auditsy Independent and separate from monitoring

y Evaluate trial conduct and compliance with the protocol, SOPs,

GCP

y Auditors are independent of the clinical trial

y Qualified by training and experience, documented

y Written audit SOP

y What, how, frequency, content of audit reports

y Audit plany Audit report



25/32


26/32

Clinical Trial Protocoly Contents include:

y Protocol title, number, date, amendment

y

Name and address of sponsor and monitory Name and title of person authorized to sign the protocol and

amendments for the sponsor

y Name and title of the investigator(s), contact information of the

sites (may be in a separate document)

y

Clinical laboratory information and other medical/technicaldepartments involved in the trial



27/32

Clinical Trial Protocoly Background information

y Trial objectives and purpose

y Trial Design

y Specific statement of the primary and secondary endpoints

y Type/design of trial to be conducted and schematic diagram

of trial design, procedures and stages

y Description of measures taken to avoid bias

y

Expected duration of subject participation, includingdiscontinuation criteria



28/32

Clinical Trial Protocoly Selection and withdrawal of subjects

y Inclusion/exclusion criteria

y Any withdrawal criteria

y Treatment of subjects

y Treatment to be administered

y Assessment of efficacy and safety

y Specification of efficacy and safety parameters

y Procedures for recording and reporting adverse events



29/32

Clinical Trial Protocoly Statistics

y Description of the statistical methods to be employed

y Number of subjects to be enrolled, including number at each

site for multi-site trialsy Criteria for termination of a trial

y Procedure for accounting for missing, unused and unverified

data



30/32

Essential Documentsy Documents that individually and collectively permit evaluation of a

trial and the quality of the data produced.

y Demonstrate the compliance of the investigator, sponsor and

monitor with the standards of GCPy Essential documents are audited by independent auditors and

inspected by regulatory authorities (i.e., FDA) to confirm the

validity of trial conduct and integrity of data collection

y Trial Master Files should be established at the beginning of the

trial, and confirmed at the monitors close-out visit



31/32

FDA Guideline for the Monitoring of Clinical Investigations

y Monitors must be appropriately trained and qualified

y Written monitoring procedures must be in place

y A sponsor is responsible for assuring, through personal contact

between the monitor and each investigator, that the investigatorclearly understands and accepts the obligations incurred inundertaking the clinical investigation

y Prior to the initiation of a clinical trial, the sponsor shouldconduct a pre-assessment visit

y A sponsor is responsible for assuring, through personal contactbetween the monitor and each investigator, that the investigator

clearly understands and accepts the obligations incurred inundertaking the clinical investigation

y The sponsor is responsible for assuring the data submitted to theFDA are accurate and complete.

y The monitor or sponsor must maintain a record of each on-site visit(monitoring reports)



32/32

Referencesy The Nuremburg Code

y The Declaration of Helsinki

y The Belmont Report

y International Conference on Harmonization E6 - Good Clinical

Practice Guidelines

y http://www.fda.gov/ScienceResearch/SpecialTopics/Running

ClinicalTrials/GuidancesInformationSheetsandNotices/defau

lt.htm

y FDA Guideline for the Monitoring of Clinical Investigations

y http://www.fda.gov/RegulatoryInformation/Guidances/ucm12

6400.htm


Date post:	30-May-2018
Category:	Documents
Upload:	aclark1029
View:	221 times
Download:	0 times