HIV Vaccine Trial: Essential Documents for The Conduct of a Clinical Trial

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The following document may be of interest to all the parties involved im HIV

vaccine Trial in India. [Moderator]

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CH Harmonised Tripartite Guideline: Guideline For Good Clinical

Practice

(J Postgrad Med 2001; 47(4):264-267)

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. 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 sponsor's 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/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. Any or all of the documents addressed in this

guideline may be subject to, and should be available for, audit by

the sponsor's 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 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 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

Investigator's Brochure) 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 breaking 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 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 during the trial as evidence that all

new relevant information is documented as it becomes available

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:

- 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

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 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)

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