Practical application of the tmf reference model
- 1. Paragon Solutions, Inc. Proprietary and Confidential Practical Application of the TMF Reference Model Industry Webinar November 14, 2012 Fran Ross, Principal Consultant, Paragon Solutions Michael Agard, Senior Consultant, Paragon Solutions
- 2. Paragon Solutions, Inc. Proprietary and Confidential - 2 - 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
- 3. Paragon Solutions, Inc. Proprietary and Confidential - 3 - Paragon Solutions’ Introduction 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 Paragon is an enterprise information management solutions company that helps firms leverage information assets to achieve better business results.
- 4. Paragon Solutions, Inc. Proprietary and Confidential - 4 - 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
- 5. Other business records Why a TMF Reference Model? Supporting records generally outside TMF e.g. IP manufacturing records Other trial-related records that “permit evaluation of the conduct of the trial and quality of data produced” Minimum list of essential documents from ICH The Trial Master File e.g. safety monitoring, EDC, data mgmt, biostats • ICH GCP Section 8 identifies “The minimum list of essential documents....” • Does not provide the comprehensive contents required for TMF inspection e.g. protocol, ICF, MVR, drug shipment e.g. incorporation papers
- 6. Paragon Solutions, Inc. Proprietary and Confidential - 6 - 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 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…. Alternate names Definition / Purpose Core or Recommen ded ICH Code EDM RM Unique ID Number Sponsor Document Investigator Document 02 Central Trial Documents 02.01 Trial Documents 02.01.02 Protocol Clinical Investigation Plan (Devices) To describe the objective(s), design, methodology, statistical considerations, and organization of a trial..... Core 1.4.4 8.2.2 Full Protocol 032 X XG TMF Zone Section Artifact name
- 7. Paragon Solutions, Inc. Proprietary and Confidential - 7 - 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?
- 8. Paragon Solutions, Inc. Proprietary and Confidential - 8 - 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 Drug Information Association www.diahome.org Know thyself! Survey the landscape
- 9. Paragon Solutions, Inc. Proprietary and Confidential - 9 - 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 Survey the landscape Differentiate the Issues
- 10. Paragon Solutions, Inc. Proprietary and Confidential - 10 - 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??? Survey the landscape Differentiate the Issues Level the Playing Field
- 11. Paragon Solutions, Inc. Proprietary and Confidential - 11 - 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 Survey the landscape Differentiate the Issues Level the Playing Field Prepare the Tools
- 12. Paragon Solutions, Inc. Proprietary and Confidential - 12 - 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…” Survey the landscape Differentiate the Issues Level the Playing Field Prepare the Tools Get the Job Done
- 13. Paragon Solutions, Inc. Proprietary and Confidential - 13 - 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 Survey the landscape Differentiate the Issues Level the Playing Field Prepare the Tools Get the Job Done
- 14. Paragon Solutions, Inc. Proprietary and Confidential - 14 - 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
- 15. Paragon Solutions, Inc. Proprietary and Confidential - 15 - Core/ Recommended, Signatures, Versioning Definition / Purpose Core / Recommended Trial Oversight 01.01.08 Monitoring Plan To describe how monitoring will be implemented during the trial, including strategy for source data verification. Core Trial Oversight 01.01.09 Medical Monitoring Plan To describe how medical surveillance of trial subjects will be assured during the trial. Core Trial Oversight 01.01.10 Publication Policy To describe the policy for publishing the trial results if publication policy is not captured within the protocol. Recommended Section Artifact name Needed for Country or Site Startup Signature or Electronic Workflow? Version Control? Filter Optional
- 16. Paragon Solutions, Inc. Proprietary and Confidential - 16 - Document Lifecycle Management Where to File? Template Study Specific Country Specific Site Specific May expand the list of core documents required at a milestone
- 17. Paragon Solutions, Inc. Proprietary and Confidential - 17 - 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
- 18. Paragon Solutions, Inc. Proprietary and Confidential - 18 - 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
- 19. Paragon Solutions, Inc. Proprietary and Confidential - 19 - 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
- 20. Paragon Solutions, Inc. Proprietary and Confidential - 20 - Michael Agard, Senior Consultant, Paragon Solutions [email protected] Fran Ross, Principal Consultant, Paragon Solutions [email protected] Jeff Crawford, Director, Life Sciences, Paragon Solutions [email protected] 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 Questions and More Information