Essential Documentation
Introduction
‘Essential documents are those
documents, which individually and
collectively permit evaluation of the
conduct of the trial and the quality of
the data produced.’
International Conference on Harmonisation (ICH)
Guidelines for Good Clinical Practice
Good Clinical Practice
‘These essential documents serve to
demonstrate the compliance of an
investigator, sponsor and monitor with
the standards of Good Clinical Practice
and with all regulatory requirements’
Maintaining Good Files
“Adhering to GCP is one thing, but proving
that this has been done is another. For a trial
to be credible in the eyes of the authorities,
investigators must be able to show that the
study is in compliance with GCP guidelines.
This means documenting every study-related
action” (Hutchinson 2009).
Hutchinson (20099) 12 Golden GCP Rules for Investigators.
Canary Publications, London.
ICH guideline for Good Clinical
Practice
Booklet produced by the ICH
Secretariat
Contains a list of Essential Documents
(Section 8)
Trial file
It is a good practice to dedicate a
member of the research staff for
maintenance and updating of the trial
file.
Filing of essential documents at the
investigator/institution and sponsor sites
in a timely manner can greatly assist in
the smooth running of the trial
Version Control
It is essential that all users of a controlled
document use the most up to date version in
order to ensure that accurate procedures
are being followed at all times
It is essential that an audit trail of version
controlled documents is made available
once a document is approved for use and
subsequently reviewed and/or changed
Version control
Once approved the final version is Version
1.0 with approval date
Minor administrative changes renumbered
using decimal point i.e. 1.1, 1.2 etc with date
change
If substantial amendments are made the
version number increases incrementally with
each change to Version 2.0, Version 3.0 etc
and dated
Version Control
Updated versions of the protocol,
information sheets and consent forms
will supersede previous documents. It
is a good idea to keep a table inside
the front cover of the site file listing the
current approved documents with their
version numbers and dates.
Three Sections
The various documents are grouped
in three sections according to the
stage of the trial
Three Stages
1. Before the trial commences
2. During the clinical conduct of the trial
3. After completion or termination of the trial
We are going to look at what the
investigator/researcher needs to document,
but you also need to be aware that the trial
Sponsor will also be obliged to keep a file.
Before the Trial
Investigator File (Trial Site File, TSF)
Standard in commercial trials
Need to produce own for academic
research / ‘in-house’ studies
Investigator File
File will contain:
Signed protocol or research proposal
Patient Information Sheet (blank)
Patient Consent Form (blank)
Advertisement for patient recruitment
Trust R&D approval documentation
Ethics approval documentation
Investigator File
CV of all researchers involved
Signature/Delegation log
Access to medical notes approval
Clinical Trial Agreement (if appropriate)
Investigator’s Brochure provided by
pharmaceutical sponsor detailing
relevant and current scientific
information about the investigational
product (or other supporting data)
Investigator File
Normal values for medical/laboratory
procedures and tests
Lab Accreditation certificates/CVs
Calibration certificates for technical
equipment
Instructions and documentation for the
handling/transporting of any trial
medication and related materials
Investigator File
Standard Operating Procedures
(SOPS)
Copies of questionnaires
Letters to patient’s GP/consultant
Decoding procedures for blinded trials
Master randomisation list
Trial initiation report for sponsored
studies
During the Trial
Any protocol amendments
Any updates to Investigator Brochure,
CRF, Ethics, R&D etc.
Signed patient consent forms
All relevant correspondence
Notification of serious adverse events
Interim reports
During the Trial
Subject Identification Log
Confidential - for researcher only
Each patient’s address, date of birth,
hospital number – they may need to be
identified at a later date
Subject Enrolment Log
Documents enrolment of subjects by
trial number, subject not identified
During the Trial
Drug Dispensing Log
Drug Accountability Log
These may be held in Trial Pharmacy file, along with
code breaks if appropriate
After completion of the Trial
Final close-out monitoring reports
Decoding documentation
Completed Subject ID code list
Drug Accountability and Returns
Audit Certificate
Final Report To Ethics and R&D
Clinical study report
Recording Data
Complete the CRF fully and legibly
Use a black pen
– Any corrections should be signed and
dated, with a comment (if necessary)
– Never use tippex. The corrected data
must be visible
– The first place you write down data is
the source document. Do not use
scraps of paper, paper towels, hands
etc
Trial Files and Archives
The investigator should set up study-
specific files in which all appropriate
documentation is filed
All study documents must be stored in a
safe, secure and confidential environment
Avoid leaving files lying around
Treat source documents like ‘gold’ and
ensure that they do not get lost or
destroyed prematurely. Keep for up to 15
years
Includes medical notes, X-rays, tissue
samples, CRFs
Data Quality
All trial data needs to be recorded
accurately in the CRFs, medical notes and
any questionnaires
The success of every clinical trial is
dependent on the reliability and quality of
the data collected and analysed
If this data is not documented accurately it
will affect all aspects of the research
Preparation
Labels on medical records
Inside cover; commercial and academic studies,
must include trial name and R&D number, name
of principal investigator and contact details
Label on outside cover (orange for UHW!):
medical records should not be digitised if patient
has been part of any research study
Pre-study preparation
Prepare all documentation prior to starting the
study, including making up all CRFs, having
storage for blood samples etc.
Archiving
Archiving in the context of clinical research
relates to the collection of essential
documents, which individually and
collectively permit the evaluation of the
conduct of the trial, and the quality of data
produced for long-term storage
CU ~ The Maltings
Cardiff & Vale UHB ~ Eltham Lewis
Associates, Newport
Archiving
It is the responsibility of the principal
investigator to arrange for the archiving of
research data
Where applicable, negotiate with the
commercial company a payment for the
archiving of site documents at a GCP
compliant facility
Once the study has ended, the investigator is
obliged to keep study-related documents for a
long period of time, often as long as 15 years
Good Clinical Practice
Compliance with ICH-GCP is
essential for both commercial and
in-house trials
And Finally…
Above all remember:
If it is not written down, it did not
happen!!!
If it is not documented, it doesn’t
exist.!!!
