practical application of the tmf reference model

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

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


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.


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

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


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

02Central 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..... Core1.4.48.2.2

Full Protocol 032 X XG

TMF Zone Section Artifact name


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?


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!



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


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???





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




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…”




Prepare the Tools

Get the Job Done


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




Prepare the Tools

Get the Job Done


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


Core/ Recommended, Signatures, Versioning

Definition / PurposeCore /

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


Document Lifecycle Management

Where to File?

Template

Study Specific

Country Specific

Site Specific

May expand the list of core documents required at a milestone


Specific Artifact Considerations

Artifact Phase II-IV Exploratory

IVRS-IWRS Training Documentation Yes NoOperational Procedure Manual Yes NoQuality Plan Yes NoAdjudication 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


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


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


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

mailto:[email protected]



http://tmfrefmodel.blogspot.com/

http://www.linkedin.com/groups?gid=2663204&trk=hb_side_g

http://www.diahome.org/en/News-and-Publications/Publications-and-Research/EDM-Corner.aspx









