The document discusses clinical trials and good clinical practice (GCP) guidelines. It provides definitions and explanations of key concepts. Specifically, it defines a clinical trial as an investigation in human subjects to discover or verify the effects of an investigational product. It describes GCP as international standards for clinical trial conduct that ensure data credibility and protect subject rights. The guidelines aim to harmonize standards across regions through organizations like the International Council for Harmonization. The document then outlines investigator responsibilities in areas like trial preparation, conduct, and closure to ensure compliance with GCP standards and protect subject safety and data integrity.

2. Clinical Trials is any investigation in human subjects intended to discover
or verify the clinical, pharmacological and/or other pharmacodynamic
effects of an investigational product(s), and/or to identify any adverse
reactions to an investigational product(s), and/or to study absorption,
distribution, metabolism, and excretion of an investigational product(s) with
the object of ascertaining its safety and/or efficacy. The terms clinical trial
and clinical study are synonymous.
What are Clinical Trials?
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3. What is GCP ?
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GCP (Good Clinical Practice) is a standard for the design, conduct,
performance, monitoring, auditing, recording, analyses, and reporting of
clinical trials that provides assurance that the data and reported results are
credible and accurate, and that the rights, integrity, and confidentiality of
trial subjects are protected.

4. Why GCP?
GOOD CLINICAL PRACTICE
International
Cooperation
Possibility of
publications
Protection of
rights, safety
and well-being
of trial subjects
Protection against
unreasonable
legal proceedings
Eligible data for
Healthcare
Authorities
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5. 5
Why ICH-GCP?
The birth of ICH* took place at a meeting in April 1990, hosted by EFPIA in
Brussels. Representatives of the regulatory agencies and industry
associations of Europe, Japan and the US met, primarily, to plan an
International Conference but the meeting also discussed the wider implications
and terms of reference of ICH.
At the first ICH Steering Committee (SC) meeting of ICH the Terms of
Reference were agreed and it was decided that the Topics selected for
harmonization would be divided into Safety, Quality and Efficacy to reflect the
three criteria which are the basis for approving and authorizing new medicinal
products.
*(at that time - the International Conference on Harmonization, nowadays - the
International Council for Harmonization)

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Why ICH-GCP under E6?
“E” heading means Efficacy and is concerned with the design, conduct, safety
and reporting of clinical trials.
As of November 2005, With the new codification revisions to an ICH Guideline are shown as (R1), (R2),
(R3) depending on the number of revisions. Annexes or Addenda to Guidelines have now been
incorporated into the core Guidelines and are indicated as revisions to the core Guideline (e.g., R1).

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When was ICH-GCP published? Any Addendum?
• The tripartite harmonized ICH Guideline was finalized under
Step 4 in May 1996.
This Good Clinical Practices document describes the responsibilities and
expectations of all participants in the conduct of clinical trials, including
investigators, monitors, sponsors and IRBs.
• The E6(R2) Integrated Addendum has reached Step 2 of the ICH process in
June 2015.
To complement the harmonized ICH E6 Guideline, which was finalized in May
1996, this Addendum is proposed to modernize ICH E6 to enable
implementation of innovative approaches to clinical trial design, management,
oversight, conduct, documentation, and reporting that will better ensure human
subject protection and data quality.

8. GCP requirements
•Patients’ well-being is the priority
•Clinical trials must be conducted in compliance with the scientifically well-
grounded protocols
•Preliminary Ethical Expert Review by independent ethics committees
•Patients’ Informed Consent
•High quality eligible source records and secondary data
•Safety reporting
•Study Drug Accountability
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9. Investigator’s Responsibilities
E6 Good Clinical Practice: Consolidated Guidance
4. Investigator
21 CFR Part 312: Investigational New Drug Application
(These regulations, which resemble GCP guidelines, are enforceable in the United States.)
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For studies conducted outside of the U.S.
but in ICH regions, compliance with the
provisions of GCP Guidelines ICH E6
ensures that that the studies will be
accepted for review by FDA as non-U.S.,
non-IND studies (under FDA regulations for
accepting such non-U.S., non-IND studies).
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10. Investigator’s Responsibilities according to GCP
•Responsibilities in the preparation for clinical trials
•Responsibilities during clinical trials start-up
•Responsibilities within clinical trials conduct
•Responsibilities after study closure
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11. The investigator(s) should be qualified by education, training, and
experience to assume responsibility for the proper conduct of the trial,
should meet all the qualifications specified by the applicable regulatory
requirement(s).
(GCP Guideline, 4.1.1)
Responsibilities in the preparation for clinical trials
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12. •The investigator should be thoroughly familiar with the appropriate use of the
investigational product(s), as described in the protocol, in the current
Investigator's Brochure, in the product information and in other information
sources provided by the sponsor.
•The investigator should maintain a list of appropriately qualified persons to
whom the investigator has delegated significant trial-related duties (they should
know the study protocol, the appropriate use of the investigational product(s)
and be aware of their responsibilities within the clinical trial).
(GCP Guidelines, 4.1, 4.2, 4.4)
Responsibilities in the preparation for clinical trials
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13. •Inclusion / Exclusion criteria
•Study Flowchart (describing study procedures)
Protocol Review/Assessment
Responsibilities in the preparation for clinical trials
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14. Responsibilities in the preparation for clinical trials
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15. Assess inclusion/exclusion criteria
Review Informed Consent Form
Check annual statistics records
Think how the patients would perceive the study information
Evaluate risk–benefit ratio for the patients
The investigator should be able to demonstrate (e.g., based on retrospective data)
a potential for recruiting the required number of suitable subjects within the
agreed recruitment period. (GCP Guideline, 4.2.1)
Responsibilities in the preparation for clinical trials
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16. Responsibilities during clinical trials start-up
The investigator should provide evidence of such qualifications through
up-to-date curriculum vitae and/or other relevant documentation
requested by the sponsor, the IRB/IEC, and/or the regulatory authority(ies).
(GCP Guideline, 4.1.1)
Documents to be Provided:
Curricula Vitae of the Principal Investigator and his/her Study Team
Signature (Delegation of Responsibilities) Log
FDA 1572 Form (21 CFR, 312.53)
Financial Disclosure Form (21 CFR, Part 54)
The investigator should maintain a list of appropriately qualified persons
to whom the investigator has delegated significant trial-related duties.
(GCP Guideline, 4.1.5)
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17. Responsibilities in the preparation for clinical trials
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18. Responsibilities in the preparation for clinical trials
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19. Responsibilities in the preparation for clinical trials
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20. The financial aspects of the trial should be documented in an agreement
between the sponsor and the investigator/institution.
(GCP Guidelines, 4.9.6, 8.2.4)
Study Agreement between Sponsor and:
Hospital
Principal Investigator
Responsibilities during clinical trials start-up
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21. –Responsibilities before the patients
–Responsibilities in regards to the study protocol
–Responsibilities before the Ethics Committee
–Responsibilities before the Sponsor
–Responsibility of the Medical Institution
Responsibilities within clinical trials conduct
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22. Responsibilities within clinical trials conduct
•Prior to a subject’s participation in the trial, the written informed consent
form should be signed and personally dated by the subject or by the subject's
legally acceptable representative, and by the person who conducted
the informed consent discussion.
•Neither the investigator, nor the trial staff, should coerce or unduly influence
a subject to participate or to continue to participate in a trial.
(GCP Guidelines, 4.8.8, 4.8.3)
1. Responsibilities before the patients
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23. Responsibilities within clinical trials conduct
•The investigator/institution should inform a subject when medical care is
needed for intercurrent illness(es) of which the investigator becomes aware.
•It is recommended that the investigator 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.
(GCP Guidelines, 4.3.2, 4.3.3)
1. Responsibilities before the patients
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24. Responsibilities within clinical trials conduct
1. Responsibilities before the patients
•Although a subject is not obliged to give his/her reason(s) for withdrawing
prematurely from a trial, the investigator should make a reasonable effort to
ascertain the reason(s), while fully respecting the subject's rights.
(GCP Guideline, 4.3.4)
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25. 2. Responsibilities in regards to the study protocol
Responsibilities within clinical trials conduct
•The investigator/institution should conduct the trial in compliance with the
protocol.
•The investigator should not implement any deviation from, or changes of the
protocol without agreement by the sponsor and prior review and documented
approval/favourable opinion from the IRB/IEC of an amendment, except where
necessary to eliminate an immediate hazard(s) to trial subjects, or when the
change(s) involves only logistical or administrative aspects of the trial (e.g.,
change in monitor(s), change of telephone number(s)).
(GCP Guidelines, 4.5.1, 4.5.2)
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26. Responsibilities within clinical trials conduct
2. Responsibilities in regards to the study protocol
•The investigator, or person designated by the investigator, should document
and explain any deviation from the approved protocol.
•The investigator may implement a deviation from, or a change of, the protocol
to eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC
approval/favourable opinion.
(GCP Guidelines, 4.5.3, 4.5.4)
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27. Responsibilities within clinical trials conduct
2. Responsibilities in regards to the study protocol
•As soon as possible, the implemented deviation or change, the reasons for it,
and, if appropriate, the proposed protocol amendment(s) should be submitted:
 (a) to the IRB/IEC for review and approval/favourable opinion,
 (b) to the sponsor for agreement and, if required,
 (c) to the regulatory authority(ies).
(GCP Guideline, 4.5.4)
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28. Responsibilities within clinical trials conduct
3. Responsibilities before the Ethics Committee
The investigator should promptly report to the IRB/IEC:
 (a) Deviations from, or changes of, the protocol to eliminate immediate hazards
to the trial subjects (see 3.3.7, 4.5.2, 4.5.4).
 (b) Changes increasing the risk to subjects and/or affecting significantly the
conduct of the trial (see 4.10.2).
 (c) All adverse drug reactions (ADRs) that are both serious and unexpected.
 (d) New information that may affect adversely the safety of the subjects or the
conduct of the trial.
(ICH E6, 3.3.8; 4.10.2; 4.11)
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29. Responsibilities within clinical trials conduct
3. Responsibilities before the Ethics Committee
The investigator should provide the following documents to the IRB/IEC:
 a current copy of the Investigator's Brochure or, if the Investigator's Brochure
is updated during the trial, a copy of the updated Investigator’s Brochure.
 written summaries of the trial status - annually, or more frequently, if requested
by the IRB/IEC.
 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).
(GCP Guidelines, 4.4.2; 4.10.1; 4.11.3) 29

30. Responsibilities within clinical trials conduct
4. Responsibilities before the Sponsor
• The investigator should ensure the accuracy, completeness, legibility, and
timeliness of the data reported to the sponsor in the CRFs and in all required
reports.
• Any change or correction to a CRF should be dated, initialed, and explained
(if necessary) and should not obscure the original entry (i.e. an audit trail should
be maintained).
• Data reported on the CRF, that are derived from source documents, should be
consistent with the source documents or the discrepancies should be
explained.
Upon request of the monitor, auditor, IRB/IEC, or regulatory authority, the
investigator/institution should make available for direct access all requested trial-
related records.
(GCP Guidelines, 4.9.1, 4.9.2, 4.9.3, 4.9.7)
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31. •Responsibility for investigational product(s) accountability at the trial site(s) rests
with the investigator/institution.
•The investigator should ensure that the investigational product(s) are used only
in accordance with the approved protocol.
•The investigator, or a person designated by the investigator/institution, should
explain the correct use of the investigational product(s) to each subject and
should check, at intervals appropriate for the trial, that each subject is following the
instructions properly.
(GCP Guidelines, 4.6.1, 4.6.5, 4.6.6)
Responsibilities within clinical trials conduct
4. Responsibilities before the Sponsor
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32. Responsibilities after study closure
1. Completion of the Trial
• Upon completion of the trial, the investigator, where applicable, should inform
the institution; the investigator/institution should provide the IRB/IEC with
a summary of the trial’s outcome, and the regulatory authority(ies) with any
reports required.
(GCP Guidelines, 4.13)
• The investigator/institution should maintain the trial documents as specified
in Essential Documents for the Conduct of a Clinical Trial (see 8.) and as required
by the applicable regulatory requirement(s). The investigator/institution should
take measures to prevent accidental or premature destruction of these
documents.
(GCP Guidelines, 4.9.4)
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33. Responsibilities after study closure
2. Premature Termination or Suspension of a Trial
• If the sponsor terminates or suspends a trial (see 5.21), the investigator should
promptly inform the IRB/IEC and provide the IRB/IEC a detailed written explanation
of the termination or suspension.
• If the IRB/IEC terminates or suspends its approval/favourable opinion of a trial
(see 3.1.2 and 3.3.9), the investigator/institution should promptly notify the sponsor
and provide the sponsor with a detailed written explanation of the termination
or suspension.
(GCP Guideline, 4.12)
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