Essential Documents Checklist – non-CTIMPs
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 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 study 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 study conduct and the integrity of data collected.
Instructions
This checklist can be be 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 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.
A Study Master 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 be available 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, the investigator/institution should make available for direct access all
requested study-related records 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
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Essential Documents Checklist – non-CTIMPs
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 SMF
File
To clarify which documents
Where applicable, any
translations and back translations have been translated, and to
provide evidence that the
of essential documents
X
Sponsor File
Comment
X (if related to
documents kept in
Sponsor File)
translation was appropriate.
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 X
sponsor agreement to the
(PI signed)
protocol/amendment(s) and
CRF
X
X
(PI and CI (unsigned)
signed)
Information given to study subject and any revisions thereof:
- Master Informed Consent Form To document the informed
X
X
X
To document that subjects will X
be given appropriate written
information (content and
wording) to support their ability
to give fully informed consent
X
X
consent
- Any other written information
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
Sponsor File
- Advertisement for subject
recruitment (if used)
To document that recruitment X
measures are appropriate and
not coercive
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
X
compensation to subject(s) for
study-related injury will be
available
X
X (auto)
Comment
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
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
To document that the Sponsor X
has agreed to take on
Sponsorship responsibilities
for the study
X
X(auto)
Letter of Sponsorship
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(where
required)
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
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
X
has been subject to REC
review and given favourable
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
NHS permissions (if applicable)
including application, approval
letter and correspondence
To document NHS permission X
was gained for an individual
NHS site to participate in the
study
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
X
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
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Investigator SMF
File
Sponsor File
Comment
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
Sponsor File
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
X
and eligibility to conduct study
and/or provide medical
supervision of subjects This
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 (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 X
been delegated by the site PI
to site staff. This may be
combined with the Signature
Sheet.
X
Where applicable, recommended
X
X
Where applicable
X
X
Where applicable
Interim or Annual Reports to REC Interim or annual reports
provided to REC in
and Authority(ies) (where
accordance with 4.10 (ICH
required)
Comment
GCP) and to authority(ies)
To document normal values
Normal value(s)/range(s) for
and/or ranges of the tests
medical/laboratory/technical
procedure(s) and/or test(s)
included in the Protocol, including
any updates
Medical/laboratory/technical
procedures/tests, including any
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To document competence of
facility to perform required
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
Sponsor File
Comment
test(s), and support reliability
updates
of results
- certification or
- accreditation or
- established quality control
and/or external quality
assessment or
- - other validation (where
required)
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 studyrelated 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 To document shipment dates, X
batch numbers and method of
materials and any updates*
X
Where applicable
To document identity, purity,
Certificate(s) of Analysis of
Investigational Product(s) shipped and strength of study materials
including Certificates of Analysis to be used in the study
for new batches
X
Where applicable
X
Where applicable
shipment of study-related
materials. Allows tracking of
product batch, review of
shipping conditions, and
accountability
Proof of storage condition
monitoring*
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To document that the required X
storage conditions of the study
materials are maintained at
site.
Note that this is especially
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
Sponsor File
Comment
important where storage
conditions vary from normal
practice, e.g. use of
refrigerator/freezer.
Investigational Product(s)
accountability at site *
To document that the study
X
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
Where applicable
Documentation of Investigational To document destruction of
X
X
unused material by sponsor or (if destroyed
Product destruction*
Where applicable
at site
Decoding procedures for blinded To document how, in case of
an emergency, identity of
studies
blinded investigational product
can be revealed without
breaking the blind for the
remaining subjects' treatment
Master Randomisation List
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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.
at site)
X
X
Where applicable
(third party if
applicable)
X
Where applicable
(third party if
applicable)
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
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
X
Where applicable
Final Study Close-Out Monitoring To document that all activities
required for study close-out
Report
Sponsor File
Comment
are completed, and copies of
essential documents are held
in the appropriate files
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 X
X
or significant discussions
(where required)
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.
Where applicable
Subject Screening Log
To document identification of
subjects who entered prestudy screening
Where applicable
Up to date Subject Identification
Code List
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X
To permit identification of all
X
subjects enrolled in the study
by investigator/institution in
case follow-up is required. List
X
(where
required)
Where applicable
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
Sponsor File
Comment
should be kept in a
confidential manner and for
agreed upon time.
Subject Enrolment Log
To document chronological
X
enrolment of subjects by study
number
Signed Informed Consent Forms To document that consent is
X
obtained in accordance with
GCP and protocol and dated
prior to participation of each
subject in study. Also to
document direct access
permission
Where applicable
X (where
applicable)
Source Documents
To document the existence of X
the subject and substantiate
integrity of study data
collected. To include original
documents related to the
study, to medical treatment,
and history of subject
Sample Case Report Forms and
any updates thereof
To record study related
observations.
Signed, dated and completed
Case Report Forms (CRF)
To document that the
X
investigator or authorised
(copy)
member of the investigator’s
staff confirms the observations
recorded
X
Documentation of CRF
corrections
To document all
X
changes/additions or
(copy)
corrections made to CRF after
initial data were recorded
X
Notification by originating
Notification by originating
investigator to sponsor of
X
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X
X
Where applicable
X
Where applicable
(original)
Where applicable
(original)
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Essential Documents Checklist – non-CTIMPs
Title Of Document
Purpose
Investigator SMF
File
Sponsor File
Comment
Investigator to Sponsor of Serious serious adverse events and
related reports
Adverse Events and related
reports
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 X
X
investigator, where applicable, (where required)
to regulatory authorities and
IRB(s)/IEC(s) of unexpected
serious adverse drug reactions
and of other safety information
Notification by sponsor to
Notification by Sponsor to
Investigators of safety information Investigator of safety
X
X
X
X
X
information.
Final report by Investigator to
REC where required, and where
applicable, to the Regulatory
Authority(ies)
To document completion of
the study
To document completion of
End of Study Declarations
submitted to Authority and REC at the study
the end of the study
Clinical Study Report
To document results and
interpretation of study
X
X
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.
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References
ICH GCP & EU Guideline available at http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf
(accessed: 15 August 2013)
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