The TMF Reference Model is managed under the Drug Information Association (DIA) Document and Records Management Community. The TMF Reference Model Provides Standardized Taxonomy and Metadata & outlines a reference definition of TMF content using standard Nomenclature.
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DIA Reference Model a Guidance for Good Document Management and eTMF
1. DIA Reference Model A Guidance For Good
Document Management And eTMF
Prepared By
Sagar V. Ghotekar Varsha J Sorate
Research Associate Atos Syntel Research Associate Atos Syntel
Vishal N Kushare Manmeet Singh Mandloi
Assistant Professor Research Associate TCS Ltd.
2. What is DIA Reference Model…?
The TMF Reference Model is managed under the Drug Information Association
(DIA) Document and Records Management Community. The TMF Reference
Model Provides Standardized Taxonomy and Metadata & outlines a reference
definition of TMF content using standard Nomenclature.
3. Essential Documents
Essential Documents are those documents which collectively and effectively
permits evaluation of conduct of trial and quality of data produced.
TMF
Is a collection of documentation that allows the conduct of clinical trial, the
integrity of trial data & the compliance of the trial with GCP to be evaluated.
5. March 2009
1st Meeting
June 2012:
V2.0
Device
Process-
based
Metadata
June 2010
V1.0
11 Zones
associated
with
artifacts
June 2015:
Release of
V3.0
TMF Reference Model
8. Rationales For Creation
Assessment
Required
Unmet drug
development
and medical
needs that
may be
addressed
with
processed
biomarker
Use for
Context
Proposed
use in drug
development
Biomarker
category
Benefits
Potential added
value to drug
development
Example:
Improved clinical
trial efficiency
Improved subject
safety
Risk
Anticipated
Consequences
If the biomarker is
unsuitable for its
intended use
Example:
Underpowered trial
Inappropriate
approval decision
Qualification
supporting
evidence
Including:
Biological
Rationale
Data supporting
relationship
between the
biomarker and
clinical trial
outcome of
interest
Analytical
performance
Informs the
type and level
of evidence
needed to
support
qualification
9. Rationale for the creation of a model
All companies and investigators conducting clinical trials in the
pharmaceutical/biotech industry maintain documentation for each clinical trial.
Each company has their own unique TMF structure as defined by their SOPs. No
comprehensive common model exists for managing TMF documents.
Investigators have the challenge of adapting to different formats and TMF
content organization with each clinical trial.
The burden is very high on smaller companies that usually have limited
document management expertise and limited financial resources.
10. Records and information exchange between collaborating companies is extremely
cumbersome, potentially preventing the joint venture or transfer of an
investigational product.
Regulators are challenged with varying terminology and file structures, creating
inefficiency and variability during audits.
12. DIA TMF Reference Model helps:
Companies meet the “essential documents” compliance requirements that have been
set by International Conference on Harmonization (ICH) in ICH GCP section 8.
Since the ICH GCP does not provide a comprehensive list of contents for the TMF,
the DIA TMF Reference Model provides a generally accepted structure for TMF-
related data, documents, artifacts, and activities.
The DIA TMF Reference Model allows organizations to effectively compile the
minimum list of essential documents that will serve to demonstrate the compliance
of the investigator, sponsor, and monitor with the standards of GCP
13. Who Benefits from a TMF Reference Model?
Sponsors
Investigators
Collaborators
Technical Vendors
Reg. Authorities
Including during mergers and joint
ventures
Who conduct trials
CROs and other vendors outsourced
by sponsors
System & TMF Application
developers
Consistency across sites and sponsors
would lead to more efficient, quicker
audits and approvals
15. Organization of the Model in Zones
• Trial Management
• Central Trial Documents
• Regulatory
• IRB/IEC and other Approvals
• Site Management
• IP and Trial Supplies
• Safety Reporting
• Centralized Testing
• Third Parties
• Data Management
• Statistics
16. Artifact name, Alternate names, Definition/Purpose
Artifact Name:
Document types that might be
found in the TMF. Could be
data files, documents, media,
digitalized content, etc. There
are more than 200 artifacts
defined in the model.
Alternate names: Other names that our
industry has used for the artifact.
Definition/Purpose: Text explaining the
content or the use of the artifact
16
17. Inclusion in TMF and ICH Code
Core: (if applicable to the study) must be in
the TMF as dictated by the ICH Guidelines,
regulations, or by the TMF Ref Model Team
Recommended: Does not have to be in the
TMF, but if it is collected or created, it is
recommended to be in the TMF
ICH Code: Reference to the ICH GCP
Guidelines. Notice that other sections
beyond E6 Section 8 are quoted.
18. TMF Zone Section Artifact name
Sponsor
Document
Investigator
Document
02 Central Trial Documents 02.01 Trial Documents 02.01.01 Investigator Brochure X XG
02 Central Trial Documents 02.01 Trial Documents 02.01.02 Protocol X XG
02 Central Trial Documents 02.01 Trial Documents 02.01.03 Protocol Synopsis X
NO-CS (if
applicable)
02 Central Trial Documents 02.01 Trial Documents 02.01.04 Protocol Amendment X
XG or XS (if
applicable)
02 Central Trial Documents 02.01 Trial Documents 02.01.05 Financial Disclosure Summary X NO
02 Central Trial Documents 02.01 Trial Documents 02.01.06 Insurance X XG (if applicable)
02 Central Trial Documents 02.01 Trial Documents 02.01.07 Sample Case Report Form X XG
02 Central Trial Documents 02.01 Trial Documents 02.01.10 Report of Prior Investigations NO NO
02 Central Trial Documents 02.02 Subject Documents 02.02.01 Subject Diary X XG (if applicable)
02 Central Trial Documents 02.02 Subject Documents 02.02.02 Subject Questionnaire X XG (if applicable)
Investigator Site File Artifacts
Investigator vs Sponsor Documents
• Assessing relevance of artifact to ISF
• XS refers to artifact specific for one site
• XG refers to general artifact for all sites
• NO-CS is generally not for ISF apart from for limited countries
DIA Key
21. Why Version 3.0
• Completely reviewed by 100’s of people
• Updated Artifacts
• Updated Zones : Reassessed for Artifact belonging
• Updated Definitions
• Sub-artifact Facilitation
• TMF Reference Model User Guide
22. 36%
31%
28%
9%
58%
54%
34%
28%
0% 10% 20% 30% 40% 50% 60% 70%
CLINICAL OPERATIONS
REGULATORY AUTHORITIES
DRUG SAFETY
DATA MANAGEMENT
2015 2018
Use of Paper in TMF Management
In each areas TMF documents are managed on paper at any point in their
lifecycle.
23. Updated Definitions
Artifact name
Alternate names
(artifact also
commonly known as)
Trial Master File Plan Records Management Plan
Central File Maintenance
Plan
Filing instructions
Filing and archive plan
To describe how records for the trial will be managed and stored
during and after the trial, including study-specific processes and
documentation for archiving and destruction. To include TMF filing
structure to be used. May include TMF content list, filing structure and
chain of custody records. Artifact can include any evidence of plan
execution including, but not limited to: plan, reports, checklists, etc.
Trial Management
Plan
Project Management Plan
Clinical Development Plan
To describe overall strategy for timelines, management and conduct of
the trial and typically makes reference to other artifacts. Artifact can
include details on contingency plan covering details for site start up
planning.
Quality Plan To describe the operational techniques and activities undertaken within
the quality management system to verify that the requirements for
quality of the trial-related activities have been fulfilled. Relevant parts
may include, but not be limited to, a plan written for internal oversight
of study quality management, an audit plan, data verification steps;
also includes escalation in the event of a quality issue being identified
and all corrective and preventative actions determined. Artifact can
Definition / Purpose
24. Sub-artifact Facilitation
Artifact name
Alternate names (artifact
also commonly known as)
Trial Master File Plan Records Management Plan
Central File Maintenance Plan
Filing instructions
Filing and archive plan
Core Document List
TMF Report
TMF Transmittal Form
TMF Setup Request
Trial Management Plan Project Management Plan
Clinical Development Plan
Site Selection Strategy
Quality Plan Quality Report
Sub-artifacts
(examples of document
types different from the
artifact provided, overwrite
with your company-specific
records)
