Title: Essential Documents and the Study File (Trial Master
File/Investigator Site File)
SOP Number and Version: 8, V1
Effective Date: 26/09/2014
Review Date: 26/09/2017
Please check this is the latest version of the SOP on the Joint Research Office website:
www.ucl.ac.uk/jro.
Author:
Name: Patricia Galligan
Position: Quality Assurance Manager (Research Governance)
___________________________________
Signature
Date
Approved by:
Name: Suzanne Binks
Position: Quality Assurance Coordinator (Research Governance)
____________________________________
Signature
Date
Authorised by:
Name: Rajinder Sidhu
Position: Deputy Director of Research Support Centre
_______________________________________
Signature
Date
Essential Documents, SOP 8, V1, 18/08/14
Page 1 of 7
Revision Chronology:
Version
Number:
1
Effective
date:
26/09/2014
Reason for change:
Author:
Initial standardised SOP for use throughout UCLH.
This has superseded JRO RMG SOP 13 (Version 2).
Patricia
Galligan
ACRONYMS
ARSAC
CI
CRF
CTA
CTIMP
GCP
GTAC
HTA
ICH
ICF
IRAS
IRMER
ISF
JRO
LCRN
MHRA
MTA
NIHR
PI
PIS
REC
SAE
SSI
SOPs
TMF
Administration of Radioactive Substances Advisory Committee
Chief Investigator
Case Report Forms
Clinical Trial Agreement
Clinical Trial of an Investigational Medicinal Product
Good Clinical Practice
Gene Therapy Advisory Committee
Human Tissue Authority
International Conference on Harmonisation
Informed Consent Form
Integrated Research Application System
Ionising Radiation (Medicines Exposure) Regulation
Investigator Site File
Joint Research Office
Local Clinical Research Network
Medicines and Healthcare Products Regulatory Agency
Material Transfer Agreement
National Institute for Health Research
Principal Investigator
Patient Information Sheet
Research Ethics Committee
Serious Adverse Events
Site Specific Information
Standard Operating Procedures
Trial Master File
BACKGROUND
It is important to keep essential study documentation within a study file for quality control,
monitoring, audit and inspection purposes. The maintenance of a study file is necessary for
effective management of research studies during preparation, throughout the conduct and
after the study has ended. For clinical trials the essential documentation is kept within a
trial master file (TMF) or an investigator site file (ISF) with a dedicated individual assigned
the responsibility to maintain the documentation. The Sponsor should provide index
page(s) with the contents of the key study documents to be filed in accordance with their
SOPs and under the relevant legal requirements.
PURPOSE
Essential Documents, SOP 8, V1, 18/08/14
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This SOP ensures that essential study documentation is available within a study file
(TMF/ISF) as evidence that the data generated is complete, accurate, verifiable and
traceable. Maintenance of essential documentation demonstrates compliance with the
Clinical Trial Regulations including principles of ICH GCP and the Research Governance
Framework.
PROCEDURE
Responsib
le persons
(Who?)
Actions (When? How?)
1
2
3
4
5
6
7
8
Responsibility of Maintaining a Study File (TMF/ISF)
A study file (TMF/ISF) should be prepared at the beginning of a study and
updated throughout the lifetime of the study. The individual assigned the
responsibility for maintaining the file must be detailed in the delegation log and
authorised by the PI.
Investigator Site File Contents
The Sponsor is responsible for providing a template for site file contents page
to ensure the essential study documentation is maintained, organised and
complete. However, should the sponsor not be able to provide this the
template contents page in Appendix 1 can be used and modified as necessary
depending on the type of study involved. This template may also be used for
monitoring, auditing and inspection purposes.
Amendments
As documents are amended during the course of the trial it is important that
amendment chronologies (version control and version history logs) are
maintained and kept indicating the changes and the dates they are
implemented. Old documents must be retained and should be clearly marked
as superseded versions, and archived where possible.
Correspondence
All correspondence with the Sponsor should be printed and filed, along with
any other relevant correspondence in the investigator site file or trial master
file.
Evidence of Training & Trial Meetings
Agendas, minutes and attendance sheets from specific trial meetings and
educational training sessions should be printed and filed, or referred to in the
file note to where these documents are stored centrally.
Use of File Notes
Where essential study documentation is not available, a file note should be
created with an explanation. Also where documents are stored elsewhere (e.g.
pharmacy site file), a file note should state the exact location of where these
documents can be found. All file notes should be signed and dated.
End of Study
Before the study can be closed a review of essential documents must be
carried out and written confirmation from the Sponsor will instruct how to
proceed. See UCLH SOP 9 Study Close Down.
Storage and Archiving
The site study file (TMF/ISF) should be stored for the timeframe specified in the
protocol and agreements as required by the Sponsor. It should be stored in a
safe and secure location with restricted access to staff personnel only , in
accordance with UCLH SOP 10 Archiving of Investigator Site File and
Pharmacy Site File (if applicable).
Essential Documents, SOP 8, V1, 18/08/14
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Delegated
individual,
PI
Sponsor or
Delegated
individual
Delegated
individual
Delegated
individual
and
sponsor
Delegated
individual
Delegated
individual
and
Pharmacy
Delegated
individual
and
Sponsor
Delegated
individual
and
sponsor,
pharmacy
REFERENCES
SOP 9 Study Close Down
SOP 10 Archiving Investigator Site File and Pharmacy Site File (if applicable)
Joint Research Office http://www.ucl.ac.uk/jro/standingoperatingprocedures
ICH GCP
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/St
ep4/E6_R1__Guideline.pdf
Essential Documents, SOP 8, V1, 18/08/14
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APPENDICES
Appendix 1 – Site File Contents Checklist
Title:
Protocol number:
EudraCT number:
REC number:
R&D number:
ISRCTN/Clintrial.Gov number:
Chief Investigator:
Principal Investigator:
Study
Type
TABLE OF CONTENTS
Y N N/A
Comments
Contacts List
1.0 CORRESPONDENCE
1.1 Emails/Letters/Telephone
Conversation/Meetings Minutes
2.0 SPONSORSHIP / R&D APPROVAL
2.1 Scientific Peer review
2.2 Risk Assessment
2.3 Feasibility
2.4 Insurance certificate / statement
2.5 Clinicaltrials.gov or ISRCTN registration
2.6 NIHR adoption letter
2.7 NHS R&D / SSI form(s)
2.8 NHS permission
2.9 Sponsor open to recruitment letter/Sponsors
approval letter if academic or other industry, i.e. funded
by industry but sponsored by University.
3.0 AGREEMENTS AND FINANCE
3.1 Finance and costings budget template
3.2 Grant application and award letter
3.3 Signed agreements (e.g. CI, CTA/CTSA, lab,
supply, MTA)
3.4 LCRN funding letters
3.5 Invoices and payments
3.6 Reports to funder
4.0 REGULATORY APPROVALS
4.1 IRAS applications
4.2 REC Letters (provisional and favourable opinion)
4.3 MHRA Notice of Acceptance Letter OR
Email confirmation that study does not fall under the
Clinical Trial Regulations.
4.4 MHRA No objection for a clinical investigation
CTIMP
Medical
devices
4.5 HTA certificate
4.6 ARSAC research certificate / IRMER approval
Tissue
4.7 GTAC favourable opinion
Gene
therapy
Radiation
4.8 Amendment notifications
4.9 Amendment acknowledgement / approval letters
4.10 REC Annual Progress Reports
5.0 PROTOCOL
5.1 Current approved signed protocol
5.2 All previously approved versions of protocol
Essential Documents, SOP 8, V1, 18/08/14
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Or file note to where
located
5.3 Version History Log
5.4 Protocol amendments
5.5 Log of (Protocol or GCP) Deviations / Violations /
Potential Serious Breaches / Serious Breaches / Urgent
Safety Measures
5.6 Sample protocol violation and deviation form
6.0 PARTICIPANT INFORMATION
6.1 Patient Information Sheet(s)
6.2 Consent Form(s)
6.3 GP letter(s)
6.4 Patient Contact Card(s)
6.5 Patient Diary Card(s)
6.6 Signed consent forms
6.7 Version History Log
6.8 All previously approved versions of PIS, ICF and
GP letters
6.9 Patient Screening and Enrolment Log
6.10 Identification Code List
6.11 Randomisation code (if applicable)
6.12 Registration/Randomisation faxes (if applicable)
6.13 Sent GP letters
7.0 RESEARCH TEAM
7.1 Delegation Log (signed and dated)
7.2 CV / GCP certificates (signed and dated)
Or file note to where
located
Or file note to where
located
Or file note to where
located
Or file note to where
located
7.3 Staff Training Records
7.4 Research Passport(s) and issued Honorary
Research Contract(s) and/or Letter(s) of Access
8.0 PHARMACOVIGILANCE / SERIOUS ADVERSE
EVENT
8.1 SAE reporting guidelines
8.2 SUSAR/SAE Log
8.3 Sample SAE form
8.4 Completed SAE forms
8.5 24 hour contact card (if applicable)
8.6 Sponsor SOPs
8.7 Emergency Un-blinding details (if applicable)
8.8 Correspondence to Sponsor reporting SAEs
8.9 Development Safety Update Reports (annual
safety reports)
8.10 Drug company safety reports
8.11 DSMC terms of reference
8.12 DSMC meeting minutes / emails
8.13 Safety meeting minutes / emails
9.0 MONITORING AND AUDIT
9.1 Monitoring plan
9.2 Site Initiation Visit
9.3 Log of Monitoring Visits
9.3 Monitoring reports
9.4 Study close-out visit report
9.5 Audit reports / certificate
9.6 Inspection Findings
10.0 STANDARD OPERATING PROCEDURES
CTIMP
CTIMP
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10.1 Relevant SOP and applicable policies
11.0 TREATMENT RELATED DOCUMENTS
11.1 Investigator Brochure (IB)
11.2 Summary of Product Characteristics (SPC)
CTIMP
Medical
devices
CTIMP
11.3 Version History Log
11.4 Previous versions
Or file note to where
located
11.5 IMP Dossier
11.6 Sample labels
11.7 Ordering and shipping records
CTIMP
11.8 QP release
CTIMP
CTIMP
11.9 Accountability Log
11.10 Destruction Log
11.11 Pharmacy Site File
CTIMP
11.12 Essential requirements checklist
11.13 CE-mark certificate(s) and confirmation from
manufacturer the device will be used within specification
11.14 Declaration of Conformity
11.15 Technical Dossier
Medical
devices
Medical
devices
Medical
devices
Medical
devices
12.0 DATA MANAGEMENT (COLLECTION, HANDLING
& STORAGE)
12.1 Data management plan
12.2 Statistics plan
12.3 Current template CRF/data collection tool
12.4 Previous versions of CRF
12.5 Instructions for CRF completion
12.6 Copies of Completed CRFs
13.0 LABORATORY RELATED DOCUMENTS – IF
APPLICABLE
13.1 List of Labs used with contact details
13.2 List of Study specific equipment used
13.3 Lab technical procedure/test certification of
accreditation
13.4 Normal Lab reference ranges for any tests or
medical procedures in the protocol
13.5 Calibration records for technical equipment
13.6 Arrangements for collection, storage and
shipment of blood and tumour tissue specimens
13.7 Record of collected body fluids/tissue samples
13.8 Record of retained body fluids/tissue samples
13.9 Example letter requesting pathology sample
Or file note to where
located
CTIMP
CTIMP
Tissue
Tissue
Tissue
Tissue
14.0 STUDY CLOSURE AND ARCHIVING
14.1 Declaration of the End of Study
14.2 Archiving arrangements
14.3 Summary of study findings
15.0 MISCELLANEOUS
Essential Documents, SOP 8, V1, 18/08/14
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Or file note to where
located
Or file note to where
located
Or file note to where
located