ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice

8. Essential Documents for the Conduct of a Clinical Trial

8.1 Introduction

Essential Documents are those documents which individually and collectively permit
evaluation of the conduct of a trial and the quality of the data produced

The minimum list of essential documents which has been developed follows. The various
documents are grouped in three sections according to the stage of the trial during which
they will normally be generated: 1) before the clinical phase of the trial commences, 2)
during the clinical conduct of the trial, and 3) after completion or termination of the trial.

A description is given of the purpose of each document, and whether it should be filed in
either the investigator/institution or sponsor files, or both. It is acceptable to combine some
of the documents, provided the individual elements are readily identifiable

Trial master files should be established at the beginning of the trial, both at the investigator/
institution’s site and at the sponsor’s office. A final close-out of a trial can only be done
when the monitor has reviewed both investigator/institution and sponsor files and
confirmed that all necessary documents are in the appropriate files

8.2 Before the Clinical Phase of the Trial Commences

Document Description
8.2.1 Investigator’s brochure To document that relevant and current
scientific information about the
investigational product has been provided to
the investigator

8.2.2 Signed Protocol and Amendments, If To document investigator and sponsor

Any, And Sample Case Report Form (CRF) agreement to the protocol/amendment(s) and
CRF

8.2.3 Information Given To Trial Subject –

a. Informed Consent Form a. To document the informed consent
b. Patient Information Sheet b. to support their ability to give fully
informed consent
c. Advertisement c. to document that recruitment
measures are appropriate and not coercive
8.2.4 Financial Aspects of the Trial To document the financial agreement
between the investigator/institution and the
sponsor for the trial.
8.2.5 Insurance Statement (where required) To document that compensation to
subject(s) for trial-related injury will be
available.
8.2.6 Signed Agreement between Involved To document agreements (where required)
Parties
8.2.7 Dated, Documented To document that the trial has been subject
Approval/Favorable Opinion Of IRB/IEC. to IRB/IEC review and given
approval/favorable opinion.
To identify the version number and date of
the document(s)
8.2.8 I RB/IEC Composition To document that the IRB/IEC is constituted
in agreement with GCP (where required)
8.2.9 Regulatory Authority (ies) To document appropriate
Authorization/Approval/ Notification of authorization/approval/notification by the
Protocol (where required) regulatory authority (ies) has been obtained
prior to initiation of the trial in compliance
with the applicable regulatory
requirement(s) (where required)
8.2.10 Curriculum Vitae And/Or Other To document qualifications and eligibility to
Relevant Documents Evidencing conduct trial and/or provide medical
Qualifications Of Investigator(S) And Sub- supervision of subjects
Investigator(S)
8.2.11 Normal Value(S)/Range(S) For To document normal values and/or ranges of
Medical/ Laboratory/Technical the tests
Procedure(S) And/Or Test(S) Included In
The Protocol
8.2.12 Medical/Laboratory/Technical To document competence of facility to
Procedures /Tests perform required test(s), and support
reliability of results (where required)
8.2.13 Sample of Label (S) Attached to To document compliance with applicable
Investigational Product Container (S) labelling regulations and appropriateness of
instructions provided to the subjects
8.2.14 Instructions For Handling Of To document instructions needed to ensure
Investigational Product(S) And Trial- proper storage, packaging, dispensing and
Related Materials disposition of investigational products and
trial-related materials
8.2.15 Shipping Records for Investigational To document shipment dates, batch numbers
Product (S) And Trial-Related Materials and method of shipment of investigational
product(s) and trial-related materials.
Allows tracking of product batch, review of
shipping conditions, and accountability
8.2.16 Certificate(S) Of Analysis of To document identity, purity, and strength
Investigational Product (S) shipped of investigational product(s) to be used in
the trial
8.2.17 Decoding Procedures for Blinded to document how, in case of an emergency,
Trials identity of blinded investigational product
can be revealed without peaking the blind
for the remaining subjects’ treatment (third
party if applicable)
8.2.18 Master Randomization List To document method for randomization of
trial population (third party if applicable)
8.2.19 Pre-Trial Monitoring Report To document that the site is suitable for the
trial (may be combined with 8.2.20)
8.2.20 Trial Initiation Monitoring Report To document that trial procedures were
reviewed with the investigator and the
investigator’s trial staff (may be combined
with 8.2.19)

8.3 During the Clinical Conduct of the Trial

In addition to having on file the above documents, the following should be added to the
files.

8.3.1 Investigator’s brochure Updates To document that investigator is informed in

a timely manner of relevant information as it
becomes available
8.3.2 Any Revision To: To document revisions of these trial related
- Protocol/amendment and CRF documents that take effect during trial
- Informed consent form
- Any other written information provided to
subjects
- Advertisement for subject recruitment (if
used)
8.3.3 Dated, Documented -To document that the amendment(s) and/or
Approval/Favorable Opinion Of IRB/IEC of revision(s) have been subject to IRB/IEC
The Following: review and were given approval/favorable
- Protocol amendment(s) opinion. To identify the version number
- Revision of: And date of the document(s).
- Informed consent form
- Any other written information to be
provided to the subject
- Advertisement for subject recruitment (if
used)
- Any other documents given
approval/favorable opinion
- continuing review of trial (where required)
8.3.4 Regulatory Authority (ies) To document compliance with applicable
Authorizations/Approvals/Notifications regulatory requirements (where required)
Where Required For:
- Protocol amendment(s) and other
documents

8.3.5 Curriculum Vitae for New see 8.2.10

Investigator(S) And/Or Sub-Investigator(S)
8.3.6 Updates to Normal Value(S) To document normal values and ranges that
/Range(S) For Medical/ Laboratory/ are revised during the trial (see 8.2.11)
Technical Procedure(S)/Test(S) Included in
the Protocol
8.3.7 Updates of Medical /Laboratory / To document that tests remain adequate
Technical Procedures/Tests throughout the trial period
8.3.8 Documentation of Investigational see 8.2.15
Product(S) And Trial-Related Materials
Shipment
8.3.9 Certificate(S) Of Analysis for New see 8.2.16
Batches of Investigational Products
8.3.10 Monitoring Visit Reports To document site visits by and findings of,
the monitor
8.3.11 Relevant Communications Other To document any agreements or significant
Than Site Visits discussions regarding trial administration,
- Letters - meeting notes protocol violations, trial conduct, adverse
- Notes of telephone calls event (AE) reporting
8.3.12 Signed Informed Consent Forms To document that consent is obtained in
accordance with GCP and protocol and
dated prior to participation of each subject
in trial. Also to document direct access
permission
8.3.13 Source Documents To document the existence of the subject
and substantiate integrity of trial data
collected.
8.3.14 Signed, Dated and Completed Case To document that the investigator or
Report Forms (CRF) authorized member of the investigator’s
staff confirms the observations recorded
(copy and original)
8.3.15 Documentation of CRF Corrections To document all changes/additions or
corrections made to CRF after initial data
were recorded (copy and original)
8.3.16 Notification By Originating
Investigator to Sponsor Of SAE And
Related Reports
8.3.17 Notification By Sponsor And/Or
Investigator, Where Applicable, To RA
(IES) And IRB(S)/IEC(S) Of Unexpected
Serious ADR And Of Other Safety
Information
8.3.18 Notification by Sponsor to
Investigators of Safety Information
8.3.19 Interim or Annual Reports to
IRB/IEC and Authority (IES)
8.3.20 Subject Screening Log To document identification of subjects who
entered pre-trial screening (where required)
8.3.21 Subject Identification Code List To document that investigator/institution
 keeps a confidential list of names of all
subjects allocated to trial numbers on
enrolling in the trial. Allows investigator/
institution to reveal identity of any subject
8.3.22 Subject Enrolment Log To document chronological enrolment of
subjects by trial number
8.3.23 Investigational Products To document that investigational product(s)
Accountability at the Site have been used according to the protocol
8.3.24 Signature Sheet To document signatures and initials of all
persons authorized to make entries and/or
corrections on CRFs
8.3.25 Record Of Retained Body Fluids/ To document location and identification of
Tissue Samples (If Any) retained samples if assays need to be
repeated
8.4 After Completion or Termination of the Trial
After completion or termination of the trial, all of the documents identified in sections 8.2
and 8.3 should be in the file together with the following
8.4.1 Investigational Product(S) To document that the investigational
Accountability at Site product(s) have been used according to the
protocol.
To documents the final accounting of
investigational product(s) received at the
site, dispensed to subjects, returned by the
subjects, and returned to sponsor
8.4.2 Documentation of Investigational To document destruction of unused
Product Destruction investigational products by sponsor or at site
(if destroyed at site)
8.4.3 Completed Subject Identification Code to permit identification of all subjects
List enrolled in the trial in case follow-up is
required
8.4.4 Audit Certificate (if available) To document that audit was performed
8.4.5 Final Trial Close-Out Monitoring to document that all activities required for
Report trial close-out are completed, and copies of
essential documents are held in the
appropriate files
8.4.6 Treatment Allocation and Decoding To document any decoding that may have
Documentation Returned to sponsor occurred
8.4.7 Final report by investigator to to document completion of the trial
IRB/IEC where required, and where
applicable, to the regulatory authority (IES)
8.4.8 Clinical Study Report To document results and interpretation of
trial