ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL

The documents which individually and collectively allow the evaluation of the conduct of a study and the quality of the data generated. These documents demonstrate the compliance (or otherwise) of the Investigator, Sponsor and Monitor with the GCP and with other applicable regulatory requirements.

Essential Documents are needed for Sponsor’s independent audit function and inspection by the Regulatory Authority.
The various Essential Documents needed for different stages of the study are classified under three groups:

1. before the clinical phase of the study commences,
2. during the clinical conduct of the study, and
3. after completion or termination of the study.
The documents may be combined but their individual elements should be readily identifiable.
Master files containing all documents pertaining to the study should be created at the beginning of the study, at the Investigator / Institution site, Sponsor’s office, Ethics committee’s office and the CRO’s office.

Abbreviation: I- Investigator / Institute, S - Sponsor,C - CRO, E – IEC

Before the Clinical Phase of the Trial Commences :Investigators, CRO,Sponsor, IEC should have a copy of all the documents listed below.
Investigator’s brochure ( To document that relevant and current scientific information about the investigational product has been provided to the investigator )
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
Information given to trial subject ( informed consent form)

Any other written information (To document that subjects will be given appropriate information (content and wording) to support their ability to give fully informed consent )

Advertisement for subject recruitment (To document that recruitment measures are appropriate and not coercive )

Financial aspects of the trial(To document the financial agreement between the investigator/institution and the sponsor for the trial )

Insurance statement (To document that compensation to subject(s) for trial-related injury will be available
Dated, documented approval / favourable opinion of 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, Subject compensation, any other documents given approval / favourable opinion

Independent ethics committee composition( To document that the IEC is constituted in agreement with GCP)
Regulatory authority(ies) authorisation / approval / notification of protocol(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))
Curriculum vitae and/or other relevant documents evidencing qualifications of Investigator(s) and Co-Investigator / Sub-Investigator(s)
Normal value(s) / range(s) for medical / laboratory / technical procedure(s) and/or test(s) included in the protocol

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 )- I,E,C,S.
Instructions for handling of investigational product(s) and trial-related materials(To document instructions needed to ensure proper storage, packaging, dispensing and disposition of investigational products and trial-related materials)

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)
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)
Decoding procedures for blinded trials( in case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subject’s treatment )

Master randomisation list
Pre-trial monitoring report ( To document that the site is suitable for trial (may be combined with Trial initiation monitoring report)
Trial initiation monitoring report (To document that the trial procedures were reviewed with the investigator and the investigator’s trial staff ).

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.

Investigator’s brochure updates

Any revision to: protocol amendment(s) and CRF , informed consent form, any other written information provided to subjects, advertisement for subject recruitment.

Dated, documented approval / favourable opinion of Independent ethics committee (IEC) of the following: protocol amendment(s), revision(s) of: informed consent form, any other written

information provided to subject advertisement for subject recruitment(if used) any other documents given approval / favourable opinion,continuing review of trial.

Regulatory authority(ies) authorisations / approvals / notifications where required for: protocol amendment(s) and other documents -I,S,C,E

Curriculum vitae for new investigator(s) and / or sub- investigator(s) -I,S,C,E

Updates to normal value(s) / range(s) for medical / laboratory / technical procedure(s) / test(s) included in the protocol-I,S,C

Medical / laboratory / technical procedures / tests- certification or accreditation or established quality control and / or external quality assessment or other validation-I,S,C

Documentation of investigational product(s) and trial-related material shipment -I,S,C

Certificate(s) of analysis for new batches of investigational products -S,C

Monitoring visit reports -S,C

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 -I,C

Signed informed consent forms – I(Original), S& C(Copy)

Source documents – I(Original), S& C(Copy)

Signed, dated and completed case report forms (CRF) – I,E,C (Copy)

Documentation of CRF corrections- I(Original), S& C(Copy)

Notification by originating investigator to sponsor of serious adverse events and related reports- I,E,C,S

Notification by sponsor and/or investigator, where applicable, to regulatory authority(ies) and IEC(s) of unexpected serious adverse drug reactions and of other- I,E,C,S

Notification by sponsor to investigators of safety information-I,E,C,S

Interim or annual reports to IEC and authority(ies)-I,E,C,S

Subject screening log -I,E,C,S

Subject identification code list-I,E,C,S

Subject enrolment log -I,E,C,S

Investigational products accountability at the site -I,E,C,S

Signature sheet -I,E,C,S

Record of retained body fluids/ tissue samples -I,E,C,S


After Completion or Termination of the Trial :

After completion or termination of the trial, all of the documents identified should be in the file together with the following :

Investigational product(s) accountability at site- I,C,S

Documentation of investigational product destruction-I,C,S

Completed subject identification code list-I,C,S

Audit certificate- C,S

Final trial close-out monitoring report- C,S

Treatment allocation and decoding documentation(Returned to sponsor to document any decoding that may have occurred )- C,S

Final report by investigator to IEC where required, and where applicable, to the regulatory authority(ies) – I,E,C,S

Clinical study report – I,E,C,S