Practical Application of the TMF Reference Model Industry Webinar November 14, 2012
Fran Ross, Principal Consultant, Paragon Solutions Michael Agard, Senior Consultant, Paragon Solutions
Paragon Solutions, Inc. Proprietary and Confidential
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
Corporate Facts
Paragon is an enterprise information management solutions company that helps firms leverage information assets to achieve better business results.
• 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 essential documents from ICH e.g. protocol, ICF, MVR, drug shipment
Other trial-related records that “permit evaluation of the conduct of the trial and quality of data produced”
The Trial Master File
Supporting records generally outside TMF e.g. IP manufacturing records
e.g. safety monitoring, EDC, data mgmt, biostats
Other business records e.g. incorporation papers
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 TMF Zone
Section
Central Trial 02 Documents 02.01
Artifact name
Trial Documents 02.01.02
Protocol
Alternate names
Definition / Purpose
Clinical Investigation Plan (Devices)
To describe the objective(s), design, methodology, statistical considerations, and organization of a trial.....
Core or Recommen ICH Code ded
EDM RM
Unique ID Number
1.4.4 8.2.2
Full Protocol
032
Core
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…. Paragon Solutions, Inc. Proprietary and Confidential -6-
Sponsor Investigator Document Document
X
XG
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 M&A, partnerships, outsourcing • Enable team focus on trial completion, not wheel reinvention or post-study scramble OK! I’m 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 company’s 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
Differentiate the issues Survey the landscape
Differentiate the Issues
Can do! • Artifact source • Content definition • Filing responsibility • Timing requirements • SOP identification • Other metadata
•
Avoid black holes – Turf wars – Creationism – Legal holds – System revamps – Other improvement initiatives
Regions of space from which nothing, not even light, can escape
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Level the Playing Field Survey the landscape
Differentiate the Issues
Level the Playing Field
Get the buy-in • What are we doing and why? Don’t 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??? Paragon Solutions, Inc. Proprietary and Confidential - 10 -
Prepare the Tools Survey the landscape
Differentiate the Issues
Level the Playing Field
Prepare the 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 deliverables Prepare all participants for rigorous discussion Agree 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 landscape
Differentiate the Issues
Level the Playing Field
Prepare the Tools
Get the Job Done
Be vigilant for squirrels and black holes •
Structure / buckets / containers do not matter, don’t 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 they have it? • Make it personal: “If you’re in the room with an inspector…”
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Get the Job Done Survey the landscape
Differentiate the Issues
Level the Playing Field
Prepare the Tools
Get the Job 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 M&A 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 organization’s 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 Electronic Workflow?
Filter
Section Trial Oversight Trial Oversight Trial Oversight
Artifact name
Version Control?
Needed for Country or Site Startup Core / Recommended
Definition / Purpose
To describe how monitoring will be implemented during the trial, including strategy for source data verification. Core
01.01.08
Monitoring Plan
01.01.09
To describe how medical surveillance of trial subjects Medical Monitoring Plan will be assured during the trial.
01.01.10
To describe the policy for publishing the trial results if publication policy is not captured within the protocol.
Publication Policy
Core
Recommended
Optional
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Document Lifecycle Management Where to File?
Country Specific
Template
Study Specific
May expand the list of core documents required at a milestone
Site Specific Paragon Solutions, Inc. Proprietary and Confidential - 16 -
Specific Artifact Considerations Artifact
IVRS-IWRS Training Documentation Operational Procedure Manual Quality Plan Adjudication Committee Document
Phase II-IV Exploratory
Yes Yes Yes Yes
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 Paragon Solutions, Inc. Proprietary and Confidential - 17 -
No No No No
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 of translated document to the original • Which date(s) and formats are required / optional / system generated
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Metadata Madness Metadata Functions: • Search • Filter • Sort • Labels • Reports
Creation Considerations: - User Entry - Look up fields - System generated / auto-fill - CTMS Interface - 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@consultparagon.com Fran Ross, Principal Consultant, Paragon Solutions fross@consultparagon.com Jeff Crawford, Director, Life Sciences, Paragon Solutions jcrawford@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/Publications-and-Research/EDM-Corner.aspx
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