2. 2
Responsibilities of an Investigator
Qualification and
Agreements
Adequate
Resources
Medical Care of
Trial Subjects
Communication
With IRB/ ERC
Compliance with
Protocol
Drug
Accountability
Randomization &
Blinding
Informed
Consents
Records &
Reports
Safety Reporting Final Reports
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
3. 3
Investigator: Qualification & Agreements
An investigator should be:
• Qualified by education, training, and experience
• Familiar with the appropriate use of the investigational product(s),
as described in
• the protocol
• the current Investigator's Brochure
• product information
• Aware of, and complies with, GCP and the applicable regulatory
requirements.
• Able to permit monitoring/auditing by the sponsor or inspection
by the regulatory authority.
• Maintaining a list of qualified persons to whom he/she delegates
significant trial-related duties.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
4. 4
Investigator: Adequate Resources
An Investigator should:
• Demonstrate a potential for recruiting the required number of
suitable subjects within the agreed recruitment period.
• Have time to properly conduct and complete the trial within the
agreed trial period.
• Have available an adequate number of qualified staff and
adequate facilities for the foreseen duration of the trial to conduct
the trial properly and safely.
• Ensure that all persons assisting with the trial are adequately
informed about the
• Protocol
• Investigational product(s), and
• Their trial-related duties and functions
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
5. 5
Investigator: Medical Care of Trial Subjects
The investigator should:
• Be responsible for all trial-related medical decisions
• Ensure that adequate medical care is provided to a subject for any
adverse events, including clinically significant laboratory values,
related to the trial
• Advise a subject when medical care is needed for intercurrent
illness
• Inform the subject's primary physician about the subject's
participation in the trial if the subject has a primary physician and if
the subject agrees to the primary physician being informed
• Make a reasonable effort to ascertain the reason for a subject to
withdraw prematurely from a trial while fully respecting the
subject's rights.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
6. 6
Investigator: Communication with IRB
The investigator should achieve the following:
• Written and dated approval from the IRB/IEC for the trial
• Protocol or its amendments
• Informed consent form and its updates
• Subject recruitment procedures (e.g., advertisements) and
• Other written information to be provided to subjects
• Investigator should provide with a current copy of the
Investigator's Brochure
• Any updates on the Investigator's Brochure should also be
provided to the IRB/IEC.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
7. 7
Investigator: Compliance with Protocol
The investigator should:
• Conduct the trial in compliance with the protocol
• Sign the protocol, or a contract, to confirm agreement with the
sponsor
• Not deviate from, or change the protocol without agreement by the
sponsor unless:
• to eliminate an immediate risk to trial subjects
• changes involve logistical or administrative aspects of the trial
• e.g., change in monitor, change of telephone number
• Document and explain any deviation from the approved protocol
• Obtain sponsor/designee approval, as appropriate, for recruitment
or continuation of a recruited subject, when a significant protocol
deviation is observed
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
8. 8
Investigator: Medical Care of Trial Subjects
The investigator should:
• Be responsible for all trial-related medical decisions
• Ensure that adequate medical care is provided to a subject for any
adverse events, including clinically significant laboratory values,
related to the trial
• Inform a subject when medical care is needed for intercurrent
illness
• Inform the subject's primary physician about the subject's
participation in the trial if the subject has a primary physician and
if the subject agrees to the primary physician being informed
• Make a reasonable effort to ascertain the reason for a subject to
withdraw prematurely from a trial while fully respecting the
subject's rights.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
9. 9
Investigator: Investigational Product
• Responsibility for investigational product accountability at the site rests with the
investigator
• Assign duties for drug accountability to a staff under the supervision of the
investigator
• Maintain records for the investigational product at the site for:
• delivery
• inventory
• storage
• use by each subject
• product reconciliation
• return to the sponsor or alternative disposition of unused/damaged product
• Records should include dates, quantities, batch/serial numbers, expiry dates and
the unique code numbers assigned to the product and trial subjects.
• Explain the correct use of the investigational product to each subject and ensure
drug compliance.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
10. 10
Investigator: Informed Consent
• Obtain IRB/IEC approval for the Informed Consent and its
revisions
• Ensure simple language that is comprehensible by lay men
• Elaborate all aspects of the trial, its foreseeable risks to the
subject and compensations
• Allow time for the subject to make a conscious and an
informed decision
• Do not coerce or unduly influence a subject to participate or
to continue to participate in a trial
• Ensure patient privacy and confidentiality
• Legally acceptable attendants of a subject can sign on patients
behalf when the subject is a child (<7y), mentally retarded,
illiterate, etc.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
11. 11
Investigator: Records & Reports
• Ensure the accuracy, completeness, legibility, and timeliness of the data
• Data reported on the CRF, should be consistent with the source
documents
• Changes or correction to a CRF should be dated, initialed and explained
• Essential documents kept for at least 2 years after marketing approval
• The financial agreement between the sponsor and the investigator
• For monitoring or audit, all trial related records should be allowed free
access to
• Submit written summaries of the trial status to the IRB/IEC and the
sponsor
• Report any changes affecting the conduct of the trial, and/or increasing
the risk to subjects.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
12. 12
Investigator: Safety Reporting
• All serious adverse events (SAEs) should be reported immediately
• The immediate reports should be followed promptly by detailed,
written reports.
• Avoid breaching subject privacy by using unique identification
codes
• Comply with the applicable regulatory requirement related to the
reporting of unexpected serious adverse drug reactions to the
regulatory authority and the IRB/IEC.
• Adverse events and/or laboratory abnormalities identified in the
protocol as critical to safety evaluations should be reported to the
sponsor
• For reported deaths, the investigator should supply the sponsor
and the IRB/IEC with any additional requested information (e.g.,
autopsy reports and terminal medical reports.
Guidelines for Good Clinical Practice 2002
ICH Harmonised Tripartite Guideline, CPMP/ICH/135/95
