Practical Application of the TMF Reference Model

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Practical Application of theTMF Reference Model
Industry Webinar
November 14, 2012
Fran Ross, Principal Consultant, Paragon
SolutionsMichael Agard, Senior Consultant,
Paragon Solutions
Paragon Solutions, Inc. Proprietary and
Confidential
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Agenda
Introductions
TMF Reference Model
What is it and why do I need it?
Where can I find the model and related
information?
How do I get involved?
Applying the Model
Practical steps to implementation at your
organization
Content Considerations
Specific content type considerations for your
eTMF improvements
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Paragon Solutions Introduction
Paragon is an enterprise information
managementsolutions company that helps firms
leverage
information assets to achieve better
businessresults.
Corporate Facts
Privately owned, 30-year history
Professional Services and Solutions Divisions
US-Based, NJ
Headquarters
- 8 domestic and
international offices
- Overseas development
center
Dual-shore Delivery
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Polling Question 1
1A. Level of involvement in TMF Reference Model?
a) Active member
b) Interested follower
c) Know a little
d) News to me
1B. Is your organization using the TMF Reference
Model?
a) Yes, fully adopted
b) Working on it
c) Wishful thinking
d) Not likely
e) Don't yet know
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Why a TMF Reference Model?
ICH GCP Section 8 identifies The minimum list
of essential documents
Does not provide the comprehensive contents
required for TMF inspection
Minimum list of essentialdocuments from ICH
The TrialMaster File
e.g. protocol, ICF, MVR,drug shipment
Other trial-relatedrecords that permit
Supporting recordsgenerally outside TMF
evaluation of the conductof the trial and
quality ofdata produced
e.g. IP manufacturingrecords
e.g. safety monitoring, EDC, datamgmt, biostats
Other business records
e.g. incorporation papers
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TMF Reference Model background
Industry-wide effort (via DIA EDM SIAC) on
content required for TMF inspection
More than 150 companies and 250 individuals
No agency endorsement or requirement, reviewed
with positive feedback
Offers standard content, structure, naming,
definitions and metadata
Core or
Recommen
ICH
Unique ID
Sponsor
Investigator
TMF Zone
Section
Artifact name
Alternate names
Definition / Purpose
ded
Code
EDM RM
Number
Document
Document
To describe the objective(s), design,
Central Trial
Trial
Clinical Investigation
methodology, statistical considerations,
1.4.4
Full
02
Documents
02.01
Documents
02.01.02
Protocol
Plan (Devices)
and organization of a trial
Core
8.2.2
Protocol
032
X
XG
Thoroughly detailed and fairly complex
By the numbers 244 artifact rows, 30 columns
Organized by Zones and Sections
Covers trial files for biopharm and device
sponsors, sites, IIS
Details include ICH, EDM, trial process, file
level, more.
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TMF Success Strategies - Information Architecture
Robust TMF information architecture base is
mission critical
Delivers many faceted dividends, and is
foundational for both paper and electronic TMF
inspection readiness
Generates do it better ideation,
comprehension and enthusiasm
Robust TMF information architecture base is hard
work

Invest the time nailing the content,
classifications, metadata

Include and align with all content creators,
content stewards, trial and
senior management
Robust TMF information architecture is worth it
Ensure your TMF is accurate, robust
inspection ready
Mitigate the TMF effort in MA, partnerships,
outsourcing
Enable team focus on trial completion, not
wheel reinvention or post-study scramble
OK! Im ready.now what?
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Survey the landscape
Survey the
landscape
Set the table
Sell project to sr. mgmt, secure one exec
sponsor
Gather the team - represent all roles involved
in trial processes
Harvest the materials
Collect all SOPs and instructions on trial
processes
Identify your companys TMF issues
Artifact handoff confusion
Two or more original filing locations
Issues with TMF audits / inspections
Record retention clarity
Know thyself!
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Drug Information Association www.diahome.org
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Differentiate the issues
Survey the
Differentiate
landscape
the Issues
Can do!
Avoid black holes
Artifact source
- Turf wars
Content definition
- Creationism
Filing responsibility
- Legal holds
Timing requirements
- System revamps
SOP identification
- Other improvement initiatives
Other metadata
Regions of space
from which nothing,
not even light, can escape
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Level the Playing Field
Survey the
Differentiate
Level the
landscape
the Issues
Playing Field
Get the buy-in
What are we doing and why?
Dont assume TMF comprehension or standard
vocabulary
Standards and definitions - template, final,
index, artifact
TMF 101s for all participants
Respect the learning curve
Ramp up time for model comprehension and
ingestion
WIIFM???
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Prepare the Tools
Survey the
Differentiate
Level the
Prepare the
landscape
the Issues
Playing Field
Tools
Copy TMF RM for Master TMF Index, adjust columns
Rename headers and add additional columns
Lock unique number column for mapping
Create work plan, meeting schedule and
deliverablesPrepare all participants for
rigorous discussionAgree on scope and conflict
resolution
Content lifecycle final document filing, not
creation or destruction
Predetermine where the buck stops
Process for resolving disagreements
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Get the Job Done
Survey the
Differentiate
Level the
Prepare the
Get the Job
landscape
the Issues
Playing Field
Tools
Done
Be vigilant for squirrels and black holes
Structure / buckets / containers do not
matter, dont let it break the stride
Agree to and use the parking lot (outdated
SOPs, immature/broken processes)
Keep inspection readiness at forefront
Laser focus is it required for a future
inspection? Do our SOPs say we
produce it? If requested, who would be
responsible and where would theyhave it?
Make it personal If youre in the room with
an inspector
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Get the Job Done
Survey the
Differentiate
Level the
Prepare the
Get the Job
landscape
the Issues
Playing Field
Tools
Done
Work through the model trust but verify
Complete the index grid, row by row
Quick wins, reiterations, subgroups for
problem areas
Carefully consider recommended, GCP codes and
your regional regs.
Keep sr. mgmt. and executive sponsor apprised
of progress / problems / success
Apply the new standard
New TMFs Update TMF SOPs, WI, manual, apply
to electronic systems
Current TMFs Risk-based approach -
inspection, duration
Hold mapping sessions with partners/vendors
Maintain new TMF index
Safeguard the output for reuse and future
considerations, partnerships and MA
C-E-L-E-B-R-A-T-E, spread the word and thank all
participants
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Polling Question 2
2. What is the status of your organizations
eTMF?
a) We currently use eTMF
b) Actively building / implementing
c) Evaluating
d) Not considering
e) Unknown / not applicable
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Core/ Recommended, Signatures, Versioning
Signature or
ElectronicWorkflow?
Needed forCountry or Site
Filter
VersionControl?
Startup
Core /Recommended
Definition / Purpose
Section
Artifact name
Trial
To describe how monitoring will be implemented
during
Oversight
01.01.08
Monitoring Plan
the trial, including strategy for source data
verification.
Core
Trial
To describe how medical surveillance of trial
subjects
Oversight
01.01.09
Medical Monitoring Plan
will be assured during the trial.
Core
Trial
To describe the policy for publishing the trial
results if
Oversight
01.01.10
Publication Policy
publication policy is not captured within the
protocol.
Optional
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Document Lifecycle Management
Where to
File?
Country
May expandthe list of coredocumentsrequired at
amilestone
Template
Specific
StudySpecific
SiteSpecific
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Specific Artifact Considerations
Artifact
Phase II-IV
Exploratory
IVRS-IWRS Training Documentation
Yes
No
Operational Procedure Manual
Yes
No
Quality Plan
Yes
No
Adjudication Committee Document
Yes
No
Other Considerations and Examples
Therapeutic Area Specific - Oncology Database
Lock
Patient Population - Pediatric Informed
Consent Form
Country Specific - Investigator Medical
License
Controlled Substance Tracking - DEA Form 222
Company specific - Translation Explanation or
Approval
Vendor Specific - Central Lab Normals
Enhanced Access Control - Contracts
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Suggested Additions to the TMF Reference Model
Accountability - chain of custody, audit trail
File locations - central, local, site
SOP and Template relationships
Documents requiring translation and
relationship oftranslated document to the
original
Which date(s) and formats are required /
optional /system generated
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Metadata Madness
Metadata Functions
Creation Considerations

Search
- User Entry

Filter
- Look up fields

Sort
- System generated / auto-fill

Labels
- CTMS Interface

Reports
- Mandatory / Optional
Examples

Study and Protocol Data

Country and Site Data

Site Personnel Names and Roles - CVs, FDA Form
1572,

Text to differentiate the same artifact received
multiple times - Protocol Signature Pages

Creation, Approval and Revision Dates

Vendor Name and Role

IRB/EC Name

Lab Name

Financial Disclosure Form
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Questions and More Information
Michael Agard, Senior Consultant, Paragon
Solutions
magard_at_consultparagon.com
Fran Ross, Principal Consultant, Paragon
Solutions
fross_at_consultparagon.com
Jeff Crawford, Director, Life Sciences, Paragon
Solutions
jcrawford_at_consultparagon.com
TMF Reference Model links
Follow the blog - http//tmfrefmodel.blogspot.com/

LinkedIn discussion group - TMF Reference Model
Get V2.0 of the Model / In-depth Overview / Join
the Team
www.diahome.org/en/News-and-Publications/Publicati
ons-and-Research/EDM-Corner.aspx
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