|
Journal of Postgraduate Medicine, Vol. 47, Issue 4, 2001 pp.264-267 ICH Harmonised Tripartite Guideline: Guideline For Good Clinical Practice Code Number: jp01077 8. Essential Documents for The Conduct of a Clinical Trial8.1 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. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements. Essential Documents also serve a number of other important purposes. Filing essential documents at the investigator/institution and sponsor sites in a timely manner can greatly assist in the successful management of a trial by the investigator, sponsor and monitor. These documents are also the ones which are usually audited by the sponsors independent audit function and inspected by the regulatory authority (ies) as part of the process to confirm the validity of the trial conduct and the integrity of data collected. 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/institutions site and at the sponsors 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. Any or all of the documents addressed in this guideline may be subject to, and should be available for, audit by the sponsors auditor and inspection by the regulatory authority(ies). 8.2
Before the Clinical Phase of the Trial Commences
During this planning stage the following documents should be generated and
should be on file before the trial formally starts Title
of Document Purpose Located in Files of
Investigator/
Institution
Sponsor
8.2.1 Investigators pochure 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 Any, And Sample Case Report Form (CRF) To document investigator and sponsor
agreement to the protocol/amendment(s) and CRF
8.2.3 Information Given To Trial
Subject - Informed Consent Form (including all applicable translations) To document
the informed consent
-
Any Other Written Information To document that subjects will be given appropriate
written information (content and wording) to support their ability to give fully
informed consent
-
Advertisement For Subject Recruitment (if used) 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
Parties, e.g.:
-investigator/institution and sponsor
-
investigator/institution and CRO
-
sponsor and CRO
-
investigator/institution and authority(ies) (where required)
To
document agreements (where required)
8.2.7 Dated, Documented Approval/Favourable
Opinion Of Institutional Review Board (IRB) /Independent Ethics Committee (IEC)
Of The Following:
-
protocol and any amendments
-
CRF (if applicable)
-
informed consent form(s)
-
any other written information to be provided to the subject(s)
-
advertisement for subject recruitment (if used)
-
subject compensation (if any)
-
any other documents given approval/ favourable opinion
To
document that the trial has been subject to IRB/IEC review and given approval/favourable
opinion. To identify the version number and date of the document(s) 8.2.8 Institutional
Review Board/Independent Ethics Committee Composition To document that the IRB/IEC
is constituted in agreement with GCP (where required)
8.2.9 Regulatory Authority(Ies)
Authorisation/Approval/ Notification Of Protocol (where required)
To document appropriate authorisation/approval/notification
by the 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
Relevant Documents Evidencing Qualifications Of Investigator(S) And Sub-Investigator(S)
To document qualifications and eligibility to conduct trial and/or provide medical
supervision of subjects
8.2.11 Normal Value(S)/Range(S)
For Medical/ Laboratory/Technical Procedure(S) And/Or Test(S) Included In The
Protocol To document normal values and/or ranges of the tests
8.2.12 Medical/Laboratory/Technical
Procedures /Tests
-certification
or
-
accreditation or
-
established quality control and/or external quality assessment
or
-
other validation (where required)
To
document competence of facility to perform required test(s), and support reliability
of results (where required)
8.2.13 Sample Of Label(S) Attached
To Investigational Product Container(S) To document compliance with applicable
labelling regulations and appropriateness of instructions provided to the subjects
8.2.14 Instructions For Handling
Of Investigational Product(S) And Trial-Related Materials (if not included in
protocol or Investigators pochure) To document instructions needed to ensure
proper storage, packaging, dispensing and disposition of investigational products
and trial-related materials
8.2.15 Shipping Records For Investigational
Product(S) And Trial-Related Materials To document shipment dates, batch numbers
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 Investigational Product(S) Shipped To document identity, purity, and strength
of investigational product(s) to be used in the trial
8.2.17 Decoding Procedures For Blinded
Trials To document how, in case of an emergency, 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 Randomisation List
To document method for randomisation 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 investigators 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 during
the trial as evidence that all new relevant information is documented as it
becomes available
8.3.1 Investigators pochure Updates
To document that investigator is informed in a timely manner of relevant information
as it becomes available
8.3.2 Any Revision To:
-
protocol/amendment(s) and CRF
-
informed consent form
-
any other written information provided to subjects
-
advertisement for subject recruitment (if used)
To
document revisions of these trial related documents that take effect during
trial
8.3.3 Dated, Documented Approval/Favourable
Opinion Of Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
Of The Following:
-
protocol amendment(s)
-
revision(s) of:
-
informed consent form
-
any other written information to be provided to the subject
-
advertisement for subject recruitment (if used)
-
any other documents given approval/favourable opinion
-
continuing review of trial (where required)
To
document that the amendment(s) and/or revision(s) have been subject to IRB/IEC
review and were given approval/favourable opinion. To identify the version number
and date of the document(s).
8.3.4 Regulatory Authority(Ies)
Authorisations/Approvals/Notificati Ons Where Required For:
-
protocol amendment(s) and other documents
To
document compliance with applicable regulatory requirements (where required)
8.3.5 Curriculum Vitae For New Investigator(S)
And/Or Sub-Investigator(S) (see 8.2.10)
8.3.6 Updates To Normal Value(S)/Range(S)
For Medical/ Laboratory/ Technical Procedure(S)/Test(S) Included In The Protocol
To document normal values and ranges that are revised during the trial (see
8.2.11)
8.3.7 Updates Of Medical/Laboratory/Technical
Procedures/Tests
-
certification or
-
accreditation or
-
established quality control and/or external quality assessment
or
-
other validation (where required)
-
To document that tests remain adequate throughout the trial period (see 8.2.12)
(where required)
8.3.8 Documentation Of Investigational
Product(S) And Trial-Related Materials Shipment (see 8.2.15.)
8.3.9 Certificate(S) Of Analysis
For New Batches Of Investigational Products (see 8.2.16)
8.3.10 Monitoring Visit Reports
To document site visits by, and findings of, the monitor
8.3.11 Relevant Communications Other
Than Site Visits
-
letters
-
meeting notes
-
notes of telephone calls
To
document any agreements or significant discussions regarding trial administration,
protocol violations, trial conduct, adverse 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 (see 8.2.3)
8.3.13 Source Documents To document
the existence of the subject and substantiate integrity of trial data collected.
To include original documents related to the trial, to medical treatment, and
history of subject
8.3.14 Signed, Dated And Completed
Case Report Forms (CRF) To document that the investigator or authorised member
of the investigators 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 Serious Adverse Events And Related Reports Notification
by originating investigator to sponsor of serious adverse events and related
reports in accordance with 4.11
8.3.17 Notification By Sponsor And/Or
Investigator, Where Applicable, To Regulatory Authority(IES) And IRB(S)/IEC(S)
Of Unexpected Serious Adverse Drug Reactions And Of Other Safety Information
Notification by sponsor and/or investigator, where applicable, to regulatory
authorities and IRB(s)/IEC(s) of unexpected serious adverse drug reactions in
accordance with 5.17 and 4.11.1 and of other safety information in accordance
with 5.16.2 and 4.11.2 (where required)
8.3.18 Notification By Sponsor To
Investigators Of Safety Information Notification by sponsor to investigators
of safety information in accordance with 5.16.2
8.3.19 Interim Or Annual Reports
To Irb/Iec And Authority(IES) Interim or annual reports provided to IRB/IEC
in accordance with 4.10 and to authority(ies) in accordance with 5.17.3 (where
required)
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
Accountability At The Site To document that investigational product(s) have
been used according to the protocol
8.3.24 Signature Sheet To document
signatures and initials of all persons authorised to make entries and/or corrections
on CRFs
8.3.25 Record Of Retained Body Fluids/
Tissue Samples (If Any) To document location and identification of 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)
Accountability At Site To document that the investigational 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
Product Destruction To document destruction of unused investigational products
by sponsor or at site (if destroyed at site)
8.4.3 Completed Subject Identification
Code List To permit identification of all subjects enrolled in the trial in
case follow-up is required. List should be kept in a confidential manner and
for agreed upon time
8.4.4 Audit Certificate (if available)
To document that audit was performed
8.4.5 Final Trial Close-Out Monitoring
Report To document that all activities required for trial close-out are completed,
and copies of essential documents are held in the appropriate files
8.4.6 Treatment Allocation And Decoding
Documentation Returned to sponsor to document any decoding that may have occurred
8.4.7 Final report by investigator
to IRB/IEC where required, and where applicable, to the regulatory authority
(IES) To document completion of the trial
8.4.8 Clinical Study Report To document
results and interpretation of trial (if applicable) This article is also
available in full-text from http://www.jpgmonline.com/
© Copyright 2001 - Journal of
Postgraduate Medicine |
|