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
- 6. Volunteers & Reviewers • Biopharma • Venders • Consultants • CRO • Investigators Site • Device
- 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.
- 11. Collaboration of data from multiple sources
- 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
- 19. TMF Layout V1.0
- 20. eTMF Layout
- 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)
- 27. References 1. https://www.diaglobal.org/ 2. https://en.wikipedia.org/wiki/Electronic_trial_master_file 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326906/ 4. https://extranet.who.int/prequal/sites/default/files/documents/Good_ Documentation_Practices.pdf 5. https://ichgcp.net/8-essential-documents-for-the-conduct-of-a- clinical-trial/ 6. https://tmfrefmodel.com/ 7. http://www.ich.org/products/guidelines/efficacy/efficacy- single/article/good-clinical-practice.html