TRIAL MASTER FILE CHECKLIST

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TRIAL MASTER FILE CHECKLIST Powered By Docstoc
					The University of Dundee TCTU                                           Doc Ref: 004.EDCs
NHS Tayside
                                                                                Version:2.0

                                                                    Effective Date: 1/7/2009

           ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)
INSTRUCTIONS
1.This checklist should be used as a tool to identify which essential documents
should be filed in Trial Master Files (TMFs) and Investigator Site Files (ISFs), and
also which documents are required for inclusion in the Sponsor file.
2.It also serves as a file note to identify the location of essential documents for a trial.
Please complete the section at the top of page 2 to identify the location and contact
for TMFs and ISFs in Tayside, and:
a.         Send a copy for inclusion in the Sponsor file
b.         Keep a copy of this document in your TMF
3.If the location of, or contact for TMF or ISF in Tayside changes, please send an
updated copy of this checklist.

IMPORTANT NOTES
1.The essential documents listed below may not be applicable to all trials.
2.Where essential documents are missing a file note should be included to document
the reasons for this.
3.Trial Master Files and Investigator Site Files may contain additional documents that
are not in this list but are relevant to the management of a trial.
4.For some trials (e.g. single site) it may be appropriate to merge Trial Master Files
and Investigator Site Files. Please make a note if this is this case.

What are ‘Essential Documents’
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, and sponsor
with the principles of Good Clinical Practice and with all applicable regulatory
requirements. Essential Documents also serve a number of other important
purposes. For example: they can greatly assist in the successful management of a
trial by the investigators and sponsor, and they are also the ones which are usually
monitored by the sponsor and inspected by the regulatory authority(ies).

A minimum list of essential documents has been developed and is the basis of this
checklist. 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 each document, and
whether it should be filed in either the ISF, TMF and/or Sponsor file. It is acceptable
to combine some of the documents, provided the individual elements are readily
identifiable.

TMFs and ISFs should be established at the beginning of the trial, at the investigator
site and trial co-ordination site. Documents indicated for inclusion in the Sponsor file,
should be provided as they become available. Any or all of the documents
addressed in this guideline may be subject to, and should be available for inspection
by the sponsor’s monitors and regulatory authority(ies).

Trial Master File
Location:

Contact:


Investigator Site File Checklist (CTIMPs)                                       Page 1 of 7
The University of Dundee TCTU                                             Doc Ref: 004.EDCs
NHS Tayside
                                                                                  Version:2.0

                                                                      Effective Date: 1/7/2009

           ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)
Investigator Site File in Tayside
Location:

Contact:

Essential Document                           Document on File         Trial-
                                                      Sponso Phar specific
                                      TMF       ISF                   notes
                                                       r File m. file
Set-up phase (before the clinical phase of the trial commences): During this
phase the following documents should be generated & should be on file before
recruitment starts.
 Essential document checklist
                                        X                 X
Database systems validation
                                             X
Trial Management Systems Summary
Including composition and charter for
Project Management Group, Trial              X                 X
Steering Committee, Data Monitoring
Committee (where applicable)
List of relevant identifiers
e.g. funding ref, EUDRaCT no, CTA
                                             X        X        X            X
no, REC ref, Sponsor ref, R&D ref,
ISRCTN.
Letter of Sponsorship
                                             X        X        X
Investigator’s brochure
or                                           X        X        X            X
Summary Product Characteristics
Signed and dated protocol, and
amendments, if any, and sample case          X        X        X            X
report form(s)
Information to be given to trial subject,
eg. sample PILs, sample informed
                                             X        X
consent forms, advertisement for
subject recruitment
Translations and back-translations of
                                             X
trial material (where applicable)
Financial aspects of the trial (funding
application/award letter/R&D                 X        X        X
costings/UoD costings)
Insurance statement (where possible)
                                             X                 X
CI/PI declaration                            X         X       X
                                            (all)   (local)   (all)
Signed agreements between involved
parties (local and collaborating sites;      X                 X
suppliers)



Investigator Site File Checklist (CTIMPs)                                         Page 2 of 7
The University of Dundee TCTU                                                  Doc Ref: 004.EDCs
NHS Tayside
                                                                                       Version:2.0

                                                                           Effective Date: 1/7/2009

            ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)
Dated, documented approval of
Research Ethics Committee (REC),
including application form, reports &             X        X        X           X*
correspondence, and REC
composition
Site specific approvals (where
                                                  X         X       X
relevant) including applications,                                               X*
                                                 (all)   (local)   (all)
approvals, and correspondence
Clinical Trial Authorisation, including
application form, approval letter and             X        X        X           X*
correspondence
NHS R&D approval (if applicable)
                                                  X         X       X
including application, approval letter                                          X*
                                                 (all)   (local)   (all)
and correspondence
Other relevant approvals e.g. ASRAC,
PIAG, GTAC. Including application
forms, approval letters and                       X        X        X           X*
correspondence

Signed/dated CV and other
documents evidencing qualifications               X         X       X
of Investigators and Sub-Investigators           (all)   (local)   (all)
(local and collaborating sites)
Normal values/ranges for medical/lab              X         X
tests included in the protocol                   (all)   (local)
Medical/lab/technical
procedures/tests. Certification or                X         X
accreditation; established quality               (all)   (local)
control; other validation
Sample of labels attached to
medicinal products                                X        X                     X

Instructions for handling of
investigational products and trial-
related materials
Many non-commercial trials use pharmacy
supplies of
medicinal products that have a marketing
authorisation and the storage and                 X        X                     X
dispensing instructions will be part of the
pharmacy’s standard operating procedures
for handling clinical trial materials. If this
applies, provided the pharmacy SOP
conforms to the applicable legislation and
guidance, including retention of records, it
may be noted in the TMF and ISF.




Investigator Site File Checklist (CTIMPs)                                              Page 3 of 7
The University of Dundee TCTU                                    Doc Ref: 004.EDCs
NHS Tayside
                                                                         Version:2.0

                                                             Effective Date: 1/7/2009

            ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)
Documentation and Shipping records
for investigational product(s)
Many non-commercial trials use pharmacy
supplies of
medicinal products that have a marketing
authorisation and so the tracking of
product batches, shipping conditions and
                                                 X   X             X
accountability will be part of the
pharmacy’s standard operating procedures
for clinical trials. If this applies, provided
the pharmacy SOP conforms to the
applicable legislation and guidance,
including retention of records, this may be
noted in the TMF and ISF
Certificate of analysis of
investigational product(s) shipped; QP           X   X             X
release
Decoding procedures for blinded trials
                                                 X   X            X**
Master Randomisation List.
This may be a programme rather than a
list, and may be held by the trial
statistician. However, a file note should        X
document the name and contact details of
the trial statistician, and the parameters of
the randomisation.
Risk assessments and monitoring
plan                                             X   X   X

Pre-trial monitoring report
Some non-commercial trials involve
investigators and sites that the sponsor
judges that a pre-trial monitoring visit to
be unnecessary to some or all of the sites.
This should be recorded in the Sponsor           X       X
and Trial Master File. Signed
confirmation/agreement letters can also
be used to verify that a site has suitable
facilities to carry out the trial and should
be kept in the Trial Master File.




    * (previous page) Approval letter only required (not applications and
    correspondence)
** Pharmacy should hold a copy of the emergency code-break or be informed
as to the 24-hour availability of an alternative procedure
 Essential Document                     Document on File
                                                                         Trial-
                                                        Spon            specific
                                                                Phar
                                          TMF      ISF   sor             notes
                                                               m. file
                                                         file
During conduct of the trial


Investigator Site File Checklist (CTIMPs)                                Page 4 of 7
The University of Dundee TCTU                                                  Doc Ref: 004.EDCs
NHS Tayside
                                                                                       Version:2.0

                                                                           Effective Date: 1/7/2009

            ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)
Site initiation details
In some cases investigator training
meetings are held prior to the trial starting,
so a trial initiation visit may not be
necessary. Signed confirmation/agreement          X         X
letters can also be used toverify that trial     (all)   (local)
procedures have been understood. Details
and records of these should be included in
the Trial Master File.

GCP training updates; trial-specific
                                                  X         X
training
                                                 (all)   (local)
Monitoring reports, and revisions to              X         X       X
monitoring plans                                 (all)   (local)   (all)
Project Management Group, Trial
Steering Committee, Data Monitoring
Committee meeting agendas, minutes                X
and changes to composition, and/or
charter. (where applicable)
Investigator’s brochure updates
                                                  X        X        X
Any revision to:
       Protocol/amendment(s)
       CRF                                       X        X        X
       Informed consent form
       Patient information leaflets
Dated, documented approval of
independent ethical committee of :
      Protocol amendment(s)
      Revisions of Informed consent              X        X        X
        form and/or Patient/Parent
        Information Sheets
      Any other documents where
        approval required.
Regulatory authorities approvals for
                                                  X        X        X
amendments where required
Curriculum vitae for new investigator
                                                  X         X       X
(s) and sub-investigator(s) (local and
                                                 (all)   (local)   (all)
collaborating)
Updates to normal values/ranges                   X         X
                                                 (all)   (local)
Updates of medical/lab/technical                  X         X
procedures/tests                                 (all)   (local)
Documentation of investigational
product                                           X         X
                                                                                X*
(including shipments and new QP                  (all)   (local)
documents)



Investigator Site File Checklist (CTIMPs)                                              Page 5 of 7
The University of Dundee TCTU                                         Doc Ref: 004.EDCs
NHS Tayside
                                                                              Version:2.0

                                                                  Effective Date: 1/7/2009

           ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)
 Documentation to show monitoring of
storage conditions of investigational                                  X*
product(s)

Relevant communication other than
site visits, eg. DMC, TSC, PMG
membership, terms of reference,              X         X
minutes. Letters inc printed emails,        (all)   (local)
meeting reports, notes of telephone
calls
Signed informed consent forms
                                                      X
Notification by originating investigator
to sponsor of serious adverse events         X        X       X
and related reports
Notification by sponsor and/or
investigator, where applicable, to
regulatory authorities of unexpected         X        X       X
serious adverse drug reactions and of
other safety information
Notification by sponsor to investigators
                                             X        X       X
of safety information
Interim or annual reports to
independent ethics committees (where
                                             X                X
required)

Subject screening log (where
required).                                            X

Delegation log
                                              X       X
Sample log (Record of retained body
                                                      X
fluids/tissue samples) (if any)


*Where investigator elects to store and dispense IMP, these documents must
be in the TMF/ISF.




Investigator Site File Checklist (CTIMPs)                                     Page 6 of 7
The University of Dundee TCTU                                                   Doc Ref: 004.EDCs
NHS Tayside
                                                                                         Version:2.0

                                                                            Effective Date: 1/7/2009

            ESSENTIAL DOCUMENT CHECKLIST (CTIMPs)

    Details                                        Document on File
                                                                     Sp           Ph       Trial-
                                                                     on            ar     specific
                                                  TMF        ISF                           notes
                                                                     sor          m.
                                                                     file         file
At end of trial

Close-out monitoring visit report
(where applicable)
Confirmation/agreement letters can be
signed to verify that all activities related to    X         X       X
trial close-out are completed and that
                                                  (all)   (local)   (all)
copies of essential documents are held in
the appropriate files and that a site visit is
not required. If this applies, it should be
noted in the Sponsor and Trial Master File.
Investigational product(s)
                                                   X         X
accountability at site                                                           X*
                                                  (all)   (local)
Documentation of investigational
products destruction
If this applies, provided the pharmacy SOP
conforms to the applicable legislation and
guidance, including retention of records, it
may be noted in the Trial Master File. For         X         X
                                                                                 X*
some trials the need for reconciliation           (all)   (local)
between medicinal products supplied, used
and returned before destruction will require
specific detailed recording if not covered by
the pharmacy
SOP.
Final report by investigator to
Independent ethics committee where
                                                   X                 X
required.

Reports to funding bodies
                                                   X                 X
Records of dissemination activity (e.g.
                                                   X
publications, presentations, posters)
Archiving arrangements
           - at sites                              X                 X
           - co-ordinating office

*Where investigator elects to store and dispense IMP, these documents must
be in the TMF/ISF.




Investigator Site File Checklist (CTIMPs)                                                Page 7 of 7

				
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