Introduction
Essential Documents are those documents, which individually and collectively permit evaluation of the conduct of a study 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 regulatoryrequirements. Essential Documents also serve a number of other important purposes. Filingessential documents at the investigator/institution and sponsor sites in a timely manner cangreatly assist in the successful management of a study by the investigator, sponsor and monitor.These documents are also the ones which are usually audited by the sponsor's independentaudit function and inspected by the regulatory authority (ies) as part of the process to confirmthe validity of the study conduct and the integrity of data collected.
Instructions
This checklist can bebe used as a tool to identify which essential documents should be filed in Study Master File (TMF) and Investigator Site File, and also which documents are required for inclusion in the Sponsor file.
The essential documents listed below may not be applicable to all studies.
Where essential documents are missing or not applicable please document the reason for this, e.g. by including a note in the comments field.
Study Master Files and Investigator Site Files may contain additional documents that are not in this list but are relevant to the management of a study.
For some studies (e.g. single site) it may be appropriate to merge Study Master File and Investigator Site File. Please make a note if this is this case.
A description is given of the purpose of each document, and whether it should be filed ineither the investigator/institution or sponsor files, or both. It is acceptable to combine some ofthe documents, provided the individual elements are readily identifiable.
A StudyMaster File should be established at the beginning of the study. A final close-out of a study can only be done when a review of both the Investigator Site File and Study Master File has been performed to confirm 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 beavailable for, audit by the sponsor’s auditor and inspection by the regulatory authority(ies).
Upon request of the monitor, auditor, Ethics Committee, or regulatory authority, theinvestigator/institution should make available for direct access all requested study-relatedrecords according to Community and national legislation.
Note: the Essential documents checklist has all documents as listed in ICH GCP and the EU recommendation on the content of the Study Master File and Archiving. Document titles may be reworded e.g. to make them UK specific; any changes are highlighted in italics. This checklist also lists documents that are expected to be part of the Study Master File, and are based on UK specific requirements and/or University of Birmingham specific procedures; these are highlighted in grey. Documents are largely grouped on topic.
Essential documents checklist:
Title Of Document / Purpose / Investigator File / SMF / Sponsor File / CommentWhere applicable, any translations and back translations of essential documents / To clarify which documents have been translated, and to provide evidence that the translation was appropriate. / X / X (if related to documents kept in Sponsor File)
Risk assessment documentation / To document the process and outcome of risk assessment, and how this informed the study set up and management. / X / Where applicable
Any plans and guidelines, e.g. Monitor Plan, Communication Plan, Statistical Analysis Plan / To document the systems put in place to address study risks and to ensure quality data is generated and the subjects’ safety and wellbeing is safeguarded. / X / Where applicable
Signed Protocol and amendments, if any, and sample Case Report Form (CRF) and any revisions / To document investigator and sponsor agreement to the protocol/amendment(s) and CRF / X
(PI signed) / X
(PI and CI signed) / X
(unsigned)
Information given to study subject and any revisions thereof:
- Master Informed Consent Form / To document the informed consent / X / X / X
- 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 / X / X / X
- Advertisement for subject recruitment (if used) / To document that recruitment measures are appropriate and not coercive / X / X / X
Financial aspects of the study
(including funding application/award letter) / To document the financial agreement between the investigator/institution and the sponsor for the study / X / X (auto)
Insurance statement
(where required) / To document that compensation to subject(s) for study-related injury will be available / X / X / X (auto)
Signed Agreement between involved parties, e.g.:
-Investigator/Institution and Sponsor (Clinical Study Site Agreements) / To document agreements / X / X / X / Where applicable, directed by Sponsor
-Investigator/Institution and third parties, eg. Vendors, coordinating centre etc / To document agreements / X / X
(where required) / X / Where applicable
-Charter signed by Data Monitoring Committee members / To document expectations of both parties, e.g. via a charter / X
-Sponsor and Chief Investigator / To document expectations of both parties, e.g. via CI Declaration Form or CI Agreement / X / X
Letter of Sponsorship / To document that the Sponsor has agreed to take on Sponsorship responsibilities for the study / X / X / X(auto)
Dated, documented Favourable Opinion of Research Ethics Committee (REC) of the following including any revisions:
-Protocol and any amendments
-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
Along with REC composition for each Favourable Ethical Opinion / To document that the study has been subject to REC review and givenfavourable opinion. To identify the version number and date of the document(s).
To document that the favourable opinion is maintained throughout the study. Documents include the application form and correspondence. / X / X / X
NHS permissions (if applicable) including application, approval letter and correspondence / To document NHS permission was gained for an individual NHS site to participate in the study / X / X / X
Other relevant approvals, e.g. ARSAC, HBRC including maintaining approval following changes to the study. application forms, approval letters and correspondence,
(where required) / To document any other appropriate approvals has been obtained prior to initiation, and to document that the authorisation is maintained throughout the study. Documents include the application form and correspondence. / X / X / X
Interim or Annual Reports to REC and Authority(ies) (where required) / Interim or annual reports provided to REC in accordance with 4.10 (ICH GCP) and to authority(ies) / X / X / X
Curriculum Vitae and/or other relevant documents evidencing qualifications of Investigator(s) and Sub-Investigator(s) including any revisions and Curriculum Vitae for new Investigators / To document qualifications and eligibility to conduct study and/or provide medical supervision of subjectsThis includes GCP training. It is recommended that you sign and date the documents as this will allow the reviewer to assess how recent the information is. / X / X / X (CI only)
Signature Sheet / To document signatures and initials of all persons authorised to make entries and/or corrections on CRFs
This may be combined with the delegation of responsibilities log. / X / X / Where applicable, recommended
Delegation of responsibilities log / To document what duties have been delegated by the site PI to site staff. This may be combined with the Signature Sheet. / X / X / Where applicable, recommended
Normal value(s)/range(s) for medical/laboratory/technical procedure(s) and/or test(s) included in the Protocol, including any updates / To document normal values and/or ranges of the tests / X / X / Where applicable
Medical/laboratory/technical procedures/tests, including any updates
-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 / X / X / Where applicable
Record of retained body fluids/ tissue samples (if any) / To document location and identification of retained samples if assays need to be repeated / X / X / Where applicable
Instructions for handling study-related materials and any updates
(If not included in Protocol) / To document instructions needed to ensure proper storage, packaging, dispensing and disposition of study-related materials / X / X / Where applicable
Shipping records for study-related materials and any updates* / To document shipment dates, batch numbers and method of shipment of study-related materials. Allows tracking of product batch, review of shipping conditions, and accountability / X / X / Where applicable
Certificate(s) of Analysis of Investigational Product(s) shipped including Certificates of Analysis for new batches / To document identity, purity, and strength of study materialsto be used in the study / X / Where applicable
Proof of storage condition monitoring* / To document that the required storage conditions of the study materials are maintained at site.
Note that this is especially important where storage conditions vary from normal practice, e.g. use of refrigerator/freezer. / X / X / Where applicable
Investigational Product(s) accountability at site * / To document that thestudy materials have been used according to the protocol. To documents the final accounting of material received at the site, dispensed to subjects, returned by the subjects, and returned to sponsor / X / X / Where applicable
Documentation of Investigational Product destruction* / To document destruction of unused material by sponsor or at site / X
(if destroyed at site) / X / Where applicable
Decoding procedures for blinded studies / 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 / X / X
(third party if applicable) / Where applicable
Master Randomisation List / To document method for randomisation of study population
Note this may be a programme rather than a list, and may be held by the Study Statistician. In this case, a Note to File should be added to the TMF, document the name and contact details of the Study Statistician, and the parameters of the randomisation. / X
(third party if applicable) / Where applicable
Treatment allocation and
decoding documentation / Returned to sponsor to document any decoding that may have occurred / X / Where applicable
Monitoring Visit Reports / To document site visits by, and findings of, the monitor / X / Where applicable
Final Study Close-Out Monitoring Report / To document that all activities required for study close-out are completed, and copies of essential documents are held in the appropriate files / X / Where applicable
Audit Certificate (if available) / To document that audit was performed / X / Where applicable
Relevant communications other than site visits
-Letters
-Meeting notes
- Notes of telephone calls / To document any agreements or significant discussions regarding study administration, protocol violations, study conduct, adverse event (AE) reporting.
Note this may include communications amongst the Study Management Group members, between Study Management Group and Data Monitoring Committee etceteras, including meeting minutes. / X
(where required) / X / Where applicable
Subject Screening Log / To document identification of subjects who entered pre-study screening / X / X
(where required) / Where applicable
Up to date Subject Identification Code List / To permit identification of all subjects enrolled in the study by investigator/institution in case follow-up is required. List should be kept in a confidential manner and for agreed upon time. / X / Where applicable
Subject Enrolment Log / To document chronological enrolment of subjects by study number / X / Where applicable
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 study. Also to document direct access permission / X / X (where applicable)
Source Documents / To document the existence of the subject and substantiate integrity of study data collected. To include original documents related to the study, to medical treatment, and history of subject / X / Where applicable
Sample Case Report Forms and any updates thereof / To record study related observations. / X / X
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 / X
(copy) / X
(original) / Where applicable
Documentation of CRF corrections / To document all changes/additions or corrections made to CRF after initial data were recorded / X
(copy) / X
(original) / Where applicable
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 / X / X
Notification by Sponsor and/or Investigator, where applicable, to Regulatory Authority(ies) and REC(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 and of other safety information / X
(where required) / X / X
Notification by Sponsor to Investigators of safety information / Notification by sponsor to Investigator of safety information. / X / X
Final report by Investigator to REC where required, and where applicable, to the Regulatory Authority(ies) / To document completion of the study / X / X
End of Study Declarations submitted to Authority and REC at the end of the study / To document completion of the study / X / X
Clinical Study Report / To document results and interpretation of study / X (if applicable) / X / X
Notes:
Columns marked‘X (auto)’: the underlying processes are dealt with by the UoB central offices (Research Governance Team, Research Finance Office) and the information will be automatically captured in the Sponsor Files.
References
ICH GCP & EU Guideline available at (accessed: 15 August 2013)
Essential Document Checklist non-CTIMPs v 1.0 / Page 1 of 11