Templates of Letters Requesting Approval by mtb29869

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									                     TMF Reference Model                                                                                                  Version 1.0                                              4-Jun-10
Each artifact includes all approvals, versions, amendments and change summaries (change control), translations and certifications.
Paper TMF presented according to Trial, Country and Site levels. For single country, combine Trial and Country.                                                                                  Applied Metadata
Core = it must be in the TMF as dictated by either the ICH Guidelines, regulations, or the TMF Reference Model group (if applicable for the trial)
Recommended = this artifact does not have to be produced, but if it is created or collected, it is recommended to be in the TMF                                                                  Inherited Metadata
Core correspondence = document any agreements or significant discussions regarding trial administration, protocol violations, trial conduct, adverse event reporting etc.




                                                                                                                                                                                                       Core or
                                                                                                                                                                                                  Recommended for ICH
     TMF Zone                 Section                     Artifact name               Alternate names                                     Definition / Purpose                                        inclusion   Code
                                                                                   Project Management     To identify overall strategy for timelines, management and conduct of the trial and
1.0 Trial Management 1.1 Trial Oversight      Trial Management Plan                Plan                   typically makes reference to other artifacts.                                          Recommended          2.2

                                                                                                          To document which standard operating procedures (SOPs) were in effect for the
1.0 Trial Management 1.1 Trial Oversight      List of SOPs Current During Trial                           duration of the trial, and trial-specific procedures created for the trial.            Core                 5.1.1
                                                                                   Study Reference
                                                                                   Manual                 To describe trial-related processes not covered by formal standard operating
1.0 Trial Management 1.1 Trial Oversight      Operational Procedure Manual         Work Instruction       procedures.                                                                            Recommended          5.1.1
                                                                                                          To document the planned subject enrolment/recruitment goals during the trial,
1.0 Trial Management 1.1 Trial Oversight      Recruitment Plan                                            including contingency plans.                                                           Recommended          5.6

1.0 Trial Management 1.1 Trial Oversight      Communication Plan                                          To document communication strategy and plans between trial stakeholders.               Recommended
                                                                                                          To describe how monitoring will be implemented during the trial, including strategy
1.0 Trial Management 1.1 Trial Oversight      Monitoring Plan                      Monitoring Data Plan   for source data verification.                                                          Core                 5.18.3
                                                                                                          To describe how medical surveillance of trial subjects will be assured during the
1.0 Trial Management 1.1 Trial Oversight      Medical Monitoring Plan                                     trial.                                                                                 Core                 5.16
                                                                                   Records Management
                                                                                   Plan
                                                                                   File plan           To document how records for the trial will be managed and stored during and after
1.0 Trial Management 1.1 Trial Oversight      Trial Master File Plan               Filing instructions the trial, including procedure and documentation for destruction.                         Recommended          5.5.7
                                                                                                       To describe how trial results will be published if publication policy is not captured
1.0 Trial Management 1.1 Trial Oversight      Publication Plan                                         within the protocol.                                                                      Recommended          6.15
                                                                                                          To certify whether the applicant, or any of its principals, is currently debarred,
                                                                                                          suspended, proposed for debarment, or declared ineligible to receive federal
                                                                                                          awards; whether within the past three years the applicant, or any of its principals,
                                                                                                          has been convicted of or had a civil judgment rendered against it for, or been
                                                                                                          indicted for, commission of fraud or certain criminal offenses; and whether the
                                                                                                          applicant has had any federal award terminated for cause or default in the past
1.0 Trial Management 1.1 Trial Oversight      Debarment Statement                                         three years.                                                                           Recommended
                                                                                                                                                                                                 Core or
                                                                                                                                                                                            Recommended for ICH
     TMF Zone                 Section                  Artifact name            Alternate names                                     Definition / Purpose                                        inclusion   Code
                                                                                                    Routine trial status progress report generated by the sponsor or 3rd Party and                                5.18.4
1.0 Trial Management 1.1 Trial Oversight   Trial Status Report                                      distributed to trial stakeholders.                                                     Recommended            (g)

1.0 Trial Management 1.1 Trial Oversight   Audit Certificate                                        To document that an audit was performed. (Does not contain the audit report.)          Core                   8.4.4
                                                                              Note to File Master
1.0 Trial Management 1.1 Trial Oversight   Filenote Master List               List                  To provide a consolidated list/index of file notes generated during the trial.      Recommended
                                                                                                    Documents developed for the purpose of tracking activities during the course of the
1.0 Trial Management 1.1 Trial Oversight   Tracking Document                                        trial.                                                                              Recommended


                                                                              Trial Team Roles and
                                                                              Responsibilities     To define trial roles, contact details and structure of the trial team; may include
                                                                              Members List         organogram; optionally this may include full and initials-only signature of all team
                                                                              Team Structure       members.
                                                                              Signature Log                                                                                                                       2.8
1.0 Trial Management 1.2 Trial Team        Trial Team Details                 Team Roster                                                                                               Core                      5.7
                                                                                                   To document qualifications and eligibility of Trial Team Members, including sponsor
1.0 Trial Management 1.2 Trial Team        Trial Team Curriculum Vitae                             and 3rd Party.                                                                       Core                      2.8
                                                                              Signature Log
1.0 Trial Management 1.2 Trial Team        Trial Team Log                     Team Roster                                                                                               Recommended
                                                                              Data Safety
                                           Independent Data Monitoring        Monitoring Board      To describe the purpose and modus operandi of the Independent Data Monitoring
1.0 Trial Management 1.3 Committees        Committee Charter                  Charter               Committee (IDMC).                                                                      Core (if applicable)   5.5.2
                                                                              Data Safety
                                           Independent Data Monitoring        Monitoring Board
1.0 Trial Management 1.3 Committees        Committee Member List              Member List           To document the current composition of the IDMC.                                       Core (if applicable)   5.5.2
                                                                              Data Safety           To document any agreements or significant decisions regarding trial conduct,
                                                                              Monitoring Board      protocol violations, adverse event reporting, to include minutes, reports,
                                           Independent Data Monitoring        Correspondence        notifications, recommendations from the IDMC. Applicable to interim and final                                 1.25
1.0 Trial Management 1.3 Committees        Committee Correspondence           IDMC Data Package     analyzes.                                                                              Core (if applicable)   5.5.2
                                                                              End Point Committee   To describe in advance the decision-making process of the Committee that will
1.0 Trial Management 1.3 Committees        Adjudication Committee Document    Document              evaluate key trial events (e.g. endpoints).                                            Core (if applicable)   5.5.2

                                                                                                    To document any agreements or significant discussions regarding trial
                                           Other (non-IDMC) Trial Committee                         administration, protocol violations, trial conduct, adverse event reporting from
1.0 Trial Management 1.3 Committees        Document                                                 committees other than IDMC. To include charter, member list and correspondence. Core (if applicable)
                                                                              Boot-up Meeting       Agenda, presentation materials and other documentation made available for
1.0 Trial Management 1.4 Meetings          Kick-off Meeting Material          Material              attendees of the trial kick-off meeting.                                         Core
                                                                                                    Trial-relevant training, including use of specialized systems, to provide evidence
                                                                                                    that trial team have appropriate qualifications and experience to conduct the trial,
1.0 Trial Management 1.4 Meetings          Trial Team Training Material                             includes evidence of training and includes all training.                               Core                   5.4.1
                                                                                                    Agenda, presentation materials and other documentation made available for                                     4.1.2
1.0 Trial Management 1.4 Meetings          Investigators Meeting Material                           attendees of the investigator meeting(s).                                              Core (if applicable)   4.2.4
                                                                                                                                                                                                Core or
                                                                                                                                                                                           Recommended for ICH
      TMF Zone              Section                     Artifact name           Alternate names                                   Definition / Purpose                                         inclusion   Code
                                                                                                  Agenda, presentation materials and other documentation generated during a trial-
                                                                                                  related meeting which documents any agreements or significant discussions
1.0 Trial Management 1.4 Meetings           Other Meeting Material                                regarding any aspect of trial management.                                               Core (if applicable)

                                                                                                  To document any agreements or significant discussions regarding the management
                                                                                                  of the trial or containing relevant information about the trial management, but not
                                                                                                  specifically listed in this Reference Model. Types of correspondence may include,
1.0 Trial Management 1.5 Communications     Correspondence                                        but not limited to: letters, memo, emails, telephone contacts.                      Core                       8.3.11



                                                                                                  To provide relevant and current clinical and non-clinical data on the investigational                          7.1
2.0 Central Trial                                                                                 product(s) that is relevant to the study of the product(s) in human subjects.                                  8.2.1
Documents            2.1 Trial Documents    Investigator Brochure          IB                     Provided to the investigator and others involved in the trial.                          Core                   8.3.1

                                                                                                  To describe the objective(s), design, methodology, statistical considerations, and
2.0 Central Trial                                                                                 organization of a trial. Usually also gives the background and rationale for the trial,                        1.4.4
Documents            2.1 Trial Documents    Protocol                                              but these could also be provided in other protocol referenced documents.                Core                   8.2.2
2.0 Central Trial                                                          Protocol Summary
Documents            2.1 Trial Documents    Protocol Synopsis              Protocol Profile       A summary of the pertinent points of the protocol.                                      Recommended
                                                                                                  To describe description of change(s) to or formal clarification of a protocol.
2.0 Central Trial                                                                                 Includes justification for a non-substantial amendment, such as administrative                                 1.4.5
Documents            2.1 Trial Documents    Summary of Protocol Changes    Protocol Amendment     changes.                                                                                Core (if applicable)   8.3.2
2.0 Central Trial                                                                                                                                                                                                8.2.2
Documents            2.1 Trial Documents    Sample Case Report Form        CRF                    Template to capture the data points of the protocol.                                    Core                   8.3.2

2.0 Central Trial                                                                                 Summary documentation of compliance with financial disclosure reporting
Documents            2.1 Trial Documents    Financial Disclosure Summary                          requirements. May include summaries, lists, other reports.                              Recommended
2.0 Central Trial
Documents            2.1 Trial Documents    Insurance                                             To document that compensation to subject(s) for trial-related injury will be available. Core                   8.2.5
2.0 Central Trial
Documents            2.2 Subject Documents Subject Diary                                          To document subject data captured away from the site.                                   Core (if applicable)
2.0 Central Trial
Documents            2.2 Subject Documents Subject Questionnaire                                  To capture specific subject related information through a series of questions.          Core (if applicable)
2.0 Central Trial                                                                                 To document that subjects will be given appropriate written information (content                               8.2.3
Documents            2.2 Subject Documents Informed Consent Form                                  and wording) to support their ability to give fully informed consent.                   Core                   8.3.2
2.0 Central Trial                                                                                 The appropriate written information (content and wording) provided to the subject                              8.2.3
Documents            2.2 Subject Documents Subject Information Sheet                              regarding the trial.                                                                    Core                   8.3.2
2.0 Central Trial                                                                                                                                                                                                8.2.3
Documents            2.2 Subject Documents Subject Participation Card                             To be provided to the subject to carry to document trial participation.                 Core (if applicable)   8.3.2
                                                                                                  To document recruitment materials used to locate subjects for participation in a
2.0 Central Trial                          Advertisements for Subject                             clinical trial; approved by the IRB/IEC to ensure measures are appropriate and not                             8.2.3
Documents            2.2 Subject Documents Recruitment                                            coercive.                                                                               Core (if applicable)   8.3.2
                                                                                                                                                                                                         Core or
                                                                                                                                                                                                    Recommended for ICH
      TMF Zone             Section                      Artifact name                Alternate names                                       Definition / Purpose                                         inclusion   Code
2.0 Central Trial                         Other Written Information Given to                               To be provided to the subject to further assist with understanding the trial                                   8.2.3
Documents           2.2 Subject Documents Subjects                                                         requirements or concepts; may include memory aids.                                      Core (if applicable)   8.3.2
                                                                                                           To describe the results and interpretation of trial of any therapeutic, prophylactic, or
                                                                                                           diagnostic agent conducted in human subjects, in which the clinical and statistical
2.0 Central Trial                                                                  Integrated Clinical &   description, presentations, and analyses are fully integrated into a single report;                            1.13
Documents           2.3 Reports             Clinical Study Report                  Statistical Report      contains data listings and summaries.                                                    Core                  8.4.8
2.0 Central Trial                                                                                          To describe in a shortened version the results and interpretation of the trial. (See
Documents           2.3 Reports             Abbreviated Clinical Study Report                              definition for Clinical Study Report)                                                    Recommended

2.0 Central Trial                                                                                          To present & summarize the relevant top line findings of the pharma-preclinical
Documents           2.3 Reports             Pharmacokinetics Report                PK Report               aspects of the final analysis. May be appended to the clinical study report (CSR).      Recommended

2.0 Central Trial                                                                  Abstract                To document a summary of the outcome of a trial, often to those outside of the
Documents           2.3 Reports             External Presentation of Data          Manuscript              sponsor company, such as at professional meetings or in professional journals.      Recommended
2.0 Central Trial                                                                                          Documents developed for the purpose of tracking activities during the course of the
Documents           2.4 Communication       Tracking Document                                              trial.                                                                              Recommended


                                                                                                           To document any agreements or significant discussions regarding the central trial
                                                                                                           documents or containing relevant information about the trial documents, but not
2.0 Central Trial                                                                                          specifically listed in this Reference Model. Types of correspondence may include,
Documents           2.4 Communication       Correspondence                                                 but not limited to: letters, memo, emails, telephone contacts.                          Core                   8.3.11
2.0 Central Trial                                                                                          To document any decision or to clarify any information relating to the central trial
Documents           2.4 Communication       Filenote                                                       documents.                                                                              Core (if applicable)



                                                                                                           A set of documents containing the initial Clinical Trial Protocol along with required
                                                                                                           regulatory forms and documents, submitted to one or more regulatory agencies
                                                                                                           requesting approval to conduct the trial, or a set of documents, along with required
                                                                                                           regulatory forms, submitted to one or more regulatory agencies for the purpose of                              8.2.9
3.0 Regulatory      3.1 Protocol Approval   CTA Submission                         IND Submission          notification, or approval of changes to the trial documents.                            Recommended            8.3.4
                                                                                                           A document received from a regulatory authority stating that the Submission has                                8.2.9
3.0 Regulatory      3.1 Protocol Approval   CTA Approval                           IND Approval            been received and approved.                                                             Core                   8.3.4
                                                                                                           Document identifying unique ID number used to uniquely identify the trial in that
                                                                                                           region, assigned by a regulatory agency – i.e., EU = EudraCT Number, FDA = IND
3.0 Regulatory      3.1 Protocol Approval   Notification of Regulatory ID Number                           Number.                                                                                 Core
                    3.2 Investigational                                                                    An application made to one or more regulatory agencies requesting a license to
3.0 Regulatory      Medicinal Product       Import License Application                                     import the investigational product and clinical supplies.                               Core (if applicable)
                    3.2 Investigational                                                                    A document issued by a national government authorizing the importation of certain
3.0 Regulatory      Medicinal Product       Import License                                                 goods into its territory.                                                               Core (if applicable)
                                                                                                                                                                                                             Core or
                                                                                                                                                                                                        Recommended for ICH
     TMF Zone                  Section                     Artifact name                   Alternate names                                      Definition / Purpose                                        inclusion   Code


                                                                                                                To assure regulatory agencies are promptly notified of all findings (new, important
                                                                                                                information on serious adverse events and or safety concerns) that could adversely
                                                                                                                affect the safety of subjects, impact the conduct of the trial or alter the regulatory
                                                                                                                authority's approval/favorable opinion to continue the trial. Notifications may include
                                               Notification to Regulatory Authority of                          but are not limited to Quarterly line listings, SUSARs, CIOMS, MedWatch, Analysis
3.0 Regulatory          3.3 Safety             Safety Information                                               of Similar Events, cover letters and/or country-specific reporting forms.               Core                  8.3.17
                                                                                                                Reports filed with Regulatory Authorities across the conduct of or at the termination
3.0 Regulatory          3.4 Communication      Report                                                           of a trial; i.e., Periodic Report, Interim Report, Annual Report.                       Core



                                                                                                                Document detailing the termination of a trial – whether upon completion or                                    4.12,
3.0 Regulatory          3.4 Communication      Notification of Trial Termination                                premature termination.                                                                 Core                   5.21
                                                                                                                To document any agreements or significant discussions with Regulatory bodies or
                                                                                                                containing relevant information about the Regulatory aspects, but not specifically
                                                                                                                listed in this Reference Model. Types of correspondence may include, but not
3.0 Regulatory          3.4 Communication      Correspondence                                                   limited to: letters, memo, emails, telephone contacts.                              Core                      8.3.11
                                                                                                                Documents developed for the purpose of tracking activities during the course of the
3.0 Regulatory          3.4 Communication      Tracking Document                                                trial.                                                                              Recommended

                                                                                                                Agenda, presentation materials and other documentation generated during an
                                                                                                                internal or external trial-related meeting which documents any agreements or
3.0 Regulatory          3.4 Communication      Meeting Material                                                 significant discussions regarding any Regulatory aspects of the trial.                 Recommended
                                                                                                                To document any decision or to clarify any information relating to the Regulatory
3.0 Regulatory          3.4 Communication      Filenote                                                         aspects of the trial.                                                                  Core (if applicable)


4.0 IRB/IEC and other   4.1 IRB/IEC Protocol                                                                    A set of documents describing the trial or changes/updates to the trial submitted to                          8.2.7
Approvals               Approval               IRB/IEC Submission                                               an IRB/IEC for approval.                                                               Recommended            8.3.3
4.0 IRB/IEC and other   4.1 IRB/IEC Protocol                                                                    Documentation received from IRB/IEC in response to submission indicating                                      8.2.7
Approvals               Approval               IRB/IEC Submission Approval                                      approval of trial and any specifications or modifications.                             Core                   8.3.3
                                                                                         Reviewer Participant
                                                                                         List                   Documentation that the IRB/IEC consists of a reasonable number of members, who
4.0 IRB/IEC and other   4.1 IRB/IEC Protocol                                             Membership List        collectively have the qualifications and experience to review and evaluate the
Approvals               Approval               IRB/IEC Composition                       Assurance Number       science, medical aspects, and ethics of the proposed trial.                      Core                         8.2.8
4.0 IRB/IEC and other   4.1 IRB/IEC Protocol   IRB/IEC Documentation of Non-Voting                              Documentation verifying non-voting members of the IRB/IEC if the investigator or
Approvals               Approval               Status                                                           sub-investigator is on the IRB/IEC.                                              Core (if applicable)         3.2.1
                                                                                                                Documentation that the IRB/IEC is performing its function according to written
4.0 IRB/IEC and other 4.1 IRB/IEC Protocol                                                                      operating procedures and is in compliance with GCP and applicable regulatory
Approvals             Approval                 IRB/IEC GCP Compliance Statement Attestation Form                requirements.                                                                          Core                   3.2.2
                                                                                                                                                                                                    Core or
                                                                                                                                                                                               Recommended for ICH
     TMF Zone                Section                     Artifact name             Alternate names                                    Definition / Purpose                                         inclusion   Code


                                                                                                     A set of documents describing the trial or changes/updates to the trial submitted to
                                                                                                     a committee other than the IRB/IEC for approval. Examples include Scientific,
4.0 IRB/IEC and other                        Other Approval Committee                                Financial, Data Protection, Biobank, Hospital Management, Health Authority. To
Approvals             4.2 Other Committees   Submission                                              include: Submissions, Correspondence and Approvals                                   Recommended
4.0 IRB/IEC and other                                                                                Documentation received from the Approval Committee in response to submission
Approvals             4.2 Other Committees   Other Approval Committee Approval                       indicating approval of trial specifications or modifications.                        Core (if applicable)
4.0 IRB/IEC and other                                                                                Reports issued to the IRB/IEC by the sponsor/3rd Party and/or investigator e.g. Line
Approvals             4.3 Communications     IRB/IEC Report                                          Listings, SUSARs, Interim Reports or Final Reports.                                  Core                       8.3.19


                                                                                                     To assure the IRB/IEC are promptly notified of all findings (new, important
                                                                                                     information on serious adverse events and or safety concerns) that could adversely
                                                                                                     affect the safety of subjects, impact the conduct of the trial or alter the IRB/IEC's
                                                                                                     approval/favorable opinion to continue the trial. Notifications may include but are
4.0 IRB/IEC and other                        Notification to IRB/IEC of Safety                       not limited to Quarterly line listings, SUSARs, CIOMS, MedWatch, Analysis of
Approvals             4.3 Communications     Information                                             Similar Events, cover letters and/or IRB/IEC-specific reporting forms.                Core                      8.3.17
4.0 IRB/IEC and other                        IRB/IEC Notification of Trial                           Document detailing the termination of a trial – whether upon completion or                                      4.12,
Approvals             4.3 Communications     Termination                                             premature termination.                                                                Core                      5.21
                                                                                                     To document any agreements or significant discussions with IRB/RECs or
                                                                                                     containing relevant information about the IRB/REC aspects, but not specifically
4.0 IRB/IEC and other                                                                                listed in this Reference Model. Types of correspondence may include, but not
Approvals             4.3 Communications     Correspondence                                          limited to: letters, memo, emails, telephone contacts.                              Core                        8.3.11
4.0 IRB/IEC and other                                                                                Documents developed for the purpose of tracking activities during the course of the
Approvals             4.3 Communications     Tracking Document                                       trial.                                                                              Recommended

                                                                                                     Agenda, presentation materials and other documentation generated during an
4.0 IRB/IEC and other                                                                                internal or external trial-related meeting which documents any agreements or
Approvals             4.3 Communications     Meeting Material                                        significant discussions regarding any IEC / IRB aspects of the trial                     Recommended
4.0 IRB/IEC and other                                                                                To document any decision or to clarify any information relating to the IRB/IEC
Approvals             4.3 Communications     Filenote                                                aspects of the trial.                                                                    Core (if applicable)




                                                                                                     To document contact information for primary points of contact at the site (e.g.
5.0 Site Management 5.1 Site Selection       Site Contact Details                                    Principal Investigator, Institution Name, Trial Coordinator, Contracts, etc).            Recommended
                                                                                                     A document between the sponsor and an outside party (Investigator or Institution)
                                                                                                     that defines the terms and basic criteria to assure that the party (or parties)
                                                                                                     receiving confidential information will maintain confidentiality and will not use that
                                                                                                     information for any purpose other than that described in the Agreement. May also
5.0 Site Management 5.1 Site Selection       Confidentiality Agreement                               be present in the Clinical Trial Agreement                                               Core                   1.16
                                                                                 Site Selection
5.0 Site Management 5.1 Site Selection       Feasibility Documentation           Documentation       To document site feasibility for the given protocol.                                     Recommended
                                                                                                                                                                                                           Core or
                                                                                                                                                                                                      Recommended for ICH
     TMF Zone                Section                 Artifact name                   Alternate names                                        Definition / Purpose                                          inclusion   Code


                                                                                   Pre-Study Visit Report
                                                                                   Site Evaluation Visit
5.0 Site Management 5.1 Site Selection   Pre Trial Monitoring Report               Report                 To document onsite visit to determine qualification of site to participate in the trial.   Core                   8.2.19

5.0 Site Management 5.1 Site Selection   Sites Evaluated but not Selected          Investigators not used Documentation related to sites evaluated but not selected for the trial.                   Recommended
                    5.2 Site Set-up                                                IB Receipt
5.0 Site Management Documentation        Acceptance of Investigator Brochure       Confirmation           To document that IB was sent and received.                                                 Recommended
                    5.2 Site Set-up
5.0 Site Management Documentation        Protocol Signature Page                                           To document investigator and sponsor agreement to the protocol.                           Core                   8.2.2
                    5.2 Site Set-up
5.0 Site Management Documentation        Protocol Amendment Signature Page                                 To document investigator and sponsor agreement to protocol amendment(s).                  Core (if applicable)   8.2.2
                    5.2 Site Set-up                                                                        To document qualifications and eligibility of the Principal Investigator to conduct                              8.2.10
5.0 Site Management Documentation        Principal Investigator Curriculum Vitae                           trial and/or provide medical supervision of subjects.                                     Core                   8.3.5

                    5.2 Site Set-up                                                                        To document qualifications and eligibility of personnel other than the Principal
5.0 Site Management Documentation        Other Curriculum Vitae                                            Investigator to conduct trial and/or provide medical supervision of subjects.             Core (if applicable)   8.2.10
                    5.2 Site Set-up
5.0 Site Management Documentation        Medical License                                                   To document medical qualifications of the investigators.                                  Recommended
                    5.2 Site Set-up                                                                        For IND trial, 1572 must be completed globally for FDA submission. For IDE
5.0 Site Management Documentation        Form FDA1572                                                      studies, the Investigator Agreement applies.                                              Core (if applicable)   8.2.6

                                                                                                           A regulatory statement from the investigator required by certain health authorities
                    5.2 Site Set-up                                                                        e.g. includes but is not limited to „Qualified Investigator Undertaking‟ form and
5.0 Site Management Documentation        Investigator Regulatory Agreement                                 „Clinical Trial Site Information‟ form required by Health Canada                          Core (if applicable)   8.2.6
                                                                                                           To certify that no financial arrangements with an investigator have been made
                                                                                                           where study outcome could affect compensation; that the investigator has no
                                                                                                           proprietary interest in the tested product; that the investigator does not have a
                                                                                                           significant equity interest in the sponsor of the covered study; and that the
                                                                                                           investigator has not received significant payments of other sorts; and/or disclosure
                    5.2 Site Set-up                                                                        of specified financial arrangements and any steps taken to minimize the potential
5.0 Site Management Documentation        Financial Disclosure Form                                         for bias.                                                                                 Core (if applicable)   8.2.4
                    5.2 Site Set-up                                                Personal Data           To document agreement between Sponsor and Site Staff (EU); often contained in
5.0 Site Management Documentation        Data Privacy Agreement                    Consent                 Clinical Trial Agreement                                                                  Recommended


                                                                                   Clinical Trial
                                                                                   Agreement,
                                                                                   Clinical Study
                                                                                   Agreement,
                    5.2 Site Set-up                                                Investigator Financial To document agreement of trial requirements between sponsor or 3rd Party and                                      8.2.4
5.0 Site Management Documentation        Clinical Trial Agreement                  Agreement.             site/ PI. Includes indemnity unless separate document created.                             Core                   8.2.6
                                                                                                                                                                                                         Core or
                                                                                                                                                                                                    Recommended for ICH
     TMF Zone                 Section                   Artifact name             Alternate names                                          Definition / Purpose                                         inclusion   Code


                    5.2 Site Set-up                                                                       To provide legal protection in the event of an unforeseen adverse circumstance                                  8.2.4
5.0 Site Management Documentation         Indemnity                                                       arising during the course of a clinical trial. May be in Clinical Trial Agreement        Core (if applicable)   8.2.6
                                                                                                          To document agreement of trial requirements between other parties involved in the
                    5.2 Site Set-up                                                                       conduct of the trial. Includes indemnity unless separate document created. e.g.                                 8.2.4
5.0 Site Management Documentation         Other Financial Agreement                                       Pharmacy agreement, other department agreement.                                   Recommended                   8.2.6
                                                                                                          To document recognition and approval by an authorized accrediting body applying
                    5.2 Site Set-up       Laboratory Certification or                                     known acceptable standards, that the facility is competent to perform required                                  8.2.12
5.0 Site Management Documentation         Accreditation                        Qualifications             test(s), and support reliability of results.                                             Core (if applicable)   8.3.7
                                                                                                          To define acceptable limits (where 95% of the population that a laboratory serves
                    5.2 Site Set-up                                                                       will fall) for comparative interpretation that allow for medical decisions to be made;                          8.2.11
5.0 Site Management Documentation         Laboratory Normal Ranges             Reference Ranges           may be included in User Manual.                                                          Core (if applicable)   8.3.6


                                                                               Drug Release
                                                                               Document
                    5.2 Site Set-up                                            Authorization to Ship      To document approval for sites to receive drug supply / investigational medicinal
5.0 Site Management Documentation         IP Site Release Documentation        Clinical Trial Materials   product.                                                                                Recommended             5.14.2
                    5.2 Site Set-up                                            Delegation of              To document delegation by the Principal Investigator of trial specific responsibilities                         4.1.5
5.0 Site Management Documentation         Site Signature Sheet                 Authority                  to site personnel conducting the trial.                                                 Core                    8.3.24
                                                                                                          To document visit to initiate site and confirm requirements have been met to begin
                                                                               Site Initiation Visit      trial participation, and that trial procedures were reviewed with the investigator and
5.0 Site Management 5.3 Site Initiation   Trial Initiation Monitoring Report   Report                     trial personnel at the site.                                                             Core                   8.2.20

5.0 Site Management 5.3 Site Initiation   Site Training Material                                          To demonstrate material used to train sites.                                             Core (if applicable)   4.1.1
                                                                               Training completion
5.0 Site Management 5.3 Site Initiation   Site Training Documentation          documentation              To document completion of site training, including attendance and certification.         Core (if applicable)   4.1.1
                                                                                                                                                                                                                          8.3.20
5.0 Site Management 5.4 Site Management   Subject Log                                                     To anonymously list all subjects including screened, screen failures and enrolled        Core                   8.3.22
                                                                                                          To document site visits evaluating trial conduct and compliance of the site, may
5.0 Site Management 5.4 Site Management   Monitoring Visit Report                                         include follow-up letter.                                                                Core                   8.3.10

5.0 Site Management 5.4 Site Management   Visit Log                                                       To document monitoring visit dates and attendees.                                        Core

5.0 Site Management 5.4 Site Management   Investigator Newsletter                                         To inform investigative staff of the progress of the trial.                              Recommended
                                                                               Protocol Deviation
                                                                               Report                                                                                                                                     3.3.8
5.0 Site Management 5.4 Site Management   Protocol Deviations                  Deviation Log              To document non-compliance/ deviations to the protocol.                                  Core                   5.18.4
                                          Final Trial Close Out Monitoring
5.0 Site Management 5.4 Site Management   Report                                                          To document trial activities are completed for site closure prior to trial completion.   Core                   8.4.5
                                                                                                                                                                                                             Core or
                                                                                                                                                                                                        Recommended for ICH
      TMF Zone             Section                     Artifact name                   Alternate names                                          Definition / Purpose                                        inclusion   Code


                                                                                                               To assure investigators are promptly notified of all findings (new, important
                                                                                                               information on serious adverse events and or safety concerns) that could adversely
                                                                                     Dear Doctor               affect the safety of subjects, impact the conduct of the trial or alter their IRB/IEC's                        5.16.2
                                                                                     Dear Health Care          approval/favorable opinion to continue the trial. Notifications may include but are                            5.17
                                           Notification to Investigators of Safety   Provider Letter           not limited to Quarterly line listings, SUSARs, CIOMS, MedWatch, Analysis of                                   8.3.17-
5.0 Site Management 5.5 Communications     Information                               Safety Letter             Similar Events, cover letters and/or country-specific reporting forms.                  Core (if applicable)   18


                                                                                                               To document any agreements or significant discussions with investigator sites or
                                                                                                               containing relevant information about the investigator sites, but not specifically
                                                                                                               listed in this Reference Model. Types of correspondence may include, but not
5.0 Site Management 5.5 Communications     Correspondence                                                      limited to: letters, memo, emails, telephone contacts.                              Core                       8.3.11
                                                                                                               Documents developed for the purpose of tracking activities during the course of the
5.0 Site Management 5.5 Communications     Tracking Document                                                   trial.                                                                              Recommended
                                                                                                               To document any decision or to clarify any information relating to the site
5.0 Site Management 5.5 Communications     Filenote                                                            management aspects of the trial                                                     Core (if applicable)



                                                                                                               To document, minimally, written procedures which define the following as they
                                                                                                               pertain to the IP: 1) quantity of active, placebo, and/or comparator supplies needed
                                                                                     Trial Medication Plan     to fulfill the requirements of the trial protocol over the life of the trial, and 2)
6.0 IP and Trial                                                                     Clinical Trial Material   acceptable storage temperatures and conditions, storage times, reconstitution                                  2.13
Supplies            6.1 IP Documentation   IP Supply Plan                            Distribution Plan         fluids and procedures, and devices for product infusion.                             Recommended               5.13.3
                                                                                                               To instruct on how the IP should be handled during transit and stored upon arrival
                                                                                                               at the distribution center, depot, and/or trial site. The content should address
                                                                                                               expectations for adequate and safe receipt, handling, storage, dispensing, retrieval
                                                                                                               of unused product from subjects, and return of unused IP to the sponsor (or their                              5.13.2
6.0 IP and Trial                                                                                               delegate) If appropriate to the trial, includes preparation of the IP leading to                               5.14.3
Supplies            6.1 IP Documentation   IP Instructions for Handling              Pharmacy Manual           administration.                                                                      Core                      8.2.14

                                                                                                               A sample of each IP label type (for every pack and every language) to be used in
6.0 IP and Trial                                                                                               the trial; approval status must be clear; translation certificates are to be included.                         5.13.1
Supplies            6.1 IP Documentation   IP Sample Label                                                     All stages of label text development are included within this artifact.                  Core                  8.2.13
                                                                                                                                                                                                                              2.12
                                                                                                               To document identity, purity, and strength of the IP(s) to be used trial, in                                   5.13.5
6.0 IP and Trial                                                                                               accordance with the specifications of the IP, including the acceptance limits and the                          8.2.16
Supplies            6.1 IP Documentation   Certificate of Analysis                                             actual results of the tests.                                                          Core                     8.3.9
6.0 IP and Trial                                                                                               To confirm that the IP has been manufactured in accordance with the regulatory                                 2.12
Supplies            6.1 IP Documentation   GMP Certification                         QP Release                requirements of GMP.                                                                  Core                     5.13.1
                                                                                                               To confirm that any IP from another country has been manufactured and checked in
6.0 IP and Trial                           QP (Qualified Person) Certification of Regulatory Release           accordance with standards of GMP at least equivalent to those laid down in                                     2.12
Supplies            6.1 IP Documentation   Import                                 Documentation                Directive 91/356/EEC.                                                            Core (if applicable)          5.13.1
                                                                                                                                                                                                   Core or
                                                                                                                                                                                              Recommended for ICH
      TMF Zone            Section                      Artifact name            Alternate names                                     Definition / Purpose                                          inclusion   Code
6.0 IP and Trial                                                                                                                                                                                                    2.12
Supplies           6.1 IP Documentation   IP Release Documentation                                 To document all GMP technical and regulatory IP release.                                 Core                    5.14.5
                                                                                                   To document the confirmation that the IP either has been manufactured of
                                                                                                   materials of non-animal origin or if it is, is it certified that all measures have been
6.0 IP and Trial                                                                                   taken to minimize the risk of transmitting transmissible spongiform encephalopathy                               8.2.15
Supplies           6.1 IP Documentation   TSE Statement                                            (TSE) via medicinal products.                                                           Core (if applicable)     8.3.8
                                                                                                                                                                                                                    5.14.4
6.0 IP and Trial                          IP Documentation of Shipment and                         To detail inventories of shipment receipts and returns to a distribution center, depot,                          8.2.15
Supplies           6.1 IP Documentation   Return                                                   and/or trial site.                                                                      Core                     8.3.8
6.0 IP and Trial                                                                                   To document the transfer of IP between depots and sites (within or across
Supplies           6.1 IP Documentation   IP Documentation of Transfer                             protocols).                                                                             Core (if applicable)     5.14.4

6.0 IP and Trial                                                                                   To document the well described plan for the re-labeling process to occur at the
Supplies           6.1 IP Documentation   Re-labeling Documentation                                depot and/or site and confirmation records that the re-labeling occurred.                Core (if applicable)    5.14.4
                                                                                                   To document the well described plan for the recall process for the IP to occur at a
6.0 IP and Trial                                                                                   distribution center, depot and/or site; will include confirmation records that the recall
Supplies           6.1 IP Documentation   IP Recall Documentation                                  occurred.                                                                                 Core (if applicable)   5.14.4



6.0 IP and Trial
Supplies           6.1 IP Documentation   Product Quality Complaint Form                           To document or record a product complaint.                                               Core (if applicable)    5.14.4
6.0 IP and Trial                                                                                   To document transportation authorization. May include commercial invoice for
Supplies           6.1 IP Documentation   Pro forma Invoice                   Commercial Invoice   distribution.                                                                            Core                    5.14.4
                                                                                                                                                                                                                    5.14.4
6.0 IP and Trial                                                              Inventory            To document records of the dispensing IP to/from the subject and the reconciliation                              8.3.23
Supplies           6.1 IP Documentation   Accountability Documentation        Documentation        of IP prior to return to the sponsor.                                               Core                         8.4.1
                                                                                                   To document the unique storage conditions of the IP and other trial supplies at the
6.0 IP and Trial                                                                                   sponsor (if sponsor is distributing), distribution center, depot, and trial site, if
Supplies           6.1 IP Documentation   Storage Condition Documentation                          required by the available stability requirements of the IP.                              Core (if applicable)    5.14.4
                                                                                                   To record excursions for IP and other trial supplies from the acceptable pre-defined
6.0 IP and Trial                          Storage Condition Excursion                              condition range either during transit or storage at a distribution center, depot, and/or
Supplies           6.1 IP Documentation   Documentation                                            trial site.                                                                              Core (if applicable)    5.14.4
6.0 IP and Trial                                                              Certificate of       To document the confirmation of destruction of IP at the end of a trial at a
Supplies           6.1 IP Documentation   Documentation of Destruction        Destruction          distribution center, depot, and/or site .                                                Core                    5.14.4
                                                                                                   To document the randomization allocation for each subject. Used if urgent
                                                                                                   unblinding is needed, or when interim or final unblinding occurs. Treatment
6.0 IP and Trial                          Treatment Allocation and Decoding   Randomization        unblinding may be controlled by interactive response technology (IRT) and or
Supplies           6.1 IP Documentation   Documentation                       envelopes            manually using code break envelopes.                                                     Core                    5.13.4
                                                                                                                                                                                                                    5.13.4
6.0 IP and Trial                                                                                   To document the procedure to be taken should the action of breaking the blind for                                8.2.17
Supplies           6.1 IP Documentation   Unblinding Plan                                          an individual subject be urgently needed, or when interim or final unblinding occurs. Core                       8.4.3
6.0 IP and Trial                                                                                   To document the action of breaking the blind for an individual subject, urgently if                              5.13.4
Supplies           6.1 IP Documentation   Code Break                          Unblinding           needed, or when interim or final unblinding occurs.                                   Core                       8.4.6
                                                                                                                                                                                                Core or
                                                                                                                                                                                           Recommended for ICH
      TMF Zone            Section                    Artifact name              Alternate names                                     Definition / Purpose                                       inclusion   Code

                                                                                                    An agreed upon plan which defines the quantity of non-IP drug and other supplies
                                                                                                    needed to fulfill the trial protocol requirements over the life of the trial. This may
                                                                                                    include but is not limited to rescue medication, supplementary medication, pre-
6.0 IP and Trial   6.2 Non-IP                                                                       treatment, other prophylactic therapies, drug delivery supplies (IV tubing, syringes),
Supplies           Documentation         Non-IP Supply Plan                                         thermometers, and respirometers.                                                       Recommended
                                                                                                    To inventory the shipment and any returns of non-IP drug and other supplies
6.0 IP and Trial   6.2 Non-IP                                                                       needed to fulfill the trial protocol requirements to a distribution center, depot, and/or
Supplies           Documentation         Non-IP Shipment Documentation                              site.                                                                                     Recommended
6.0 IP and Trial   6.2 Non-IP            Comparator / Additional Drug                                                                                                                                            2.12
Supplies           Documentation         Information                                                To provide information on the comparator or rescue medication used in a trial.        Core (if applicable)   5.12.1


                                                                                                    To document end user requirements from design and capabilities of the interactive
                                                                                                    response technology (IRT) such as IVRS or IWRS, included by not limited to
6.0 IP and Trial   6.3 Interactive                                                                  screening, randomization, drug allocation, submitted to the vendor for analysis.
Supplies           Response Technology   IRT User Requirement Specification                         May also include technical aspects of the system development.                         Core (if applicable)   5.5.3

6.0 IP and Trial   6.3 Interactive
Supplies           Response Technology   IRT Validation Certification                               To confirm the validation status of the interactive response technology (IRT).        Core (if applicable)   5.5.3
                                                                                                    To document the acceptability of the series of assessments of the interactive
                                                                                                    response technology (IRT) performed by key users of the system that are designed
                                                                                                    to show that the IRT has been correctly programmed and meets the requirements
6.0 IP and Trial   6.3 Interactive                                            IRT UAT Scripts and   of the URS. Minimally the signature page and may include validation or other
Supplies           Response Technology   IRT UAT Certification                Sign Off              documentation.                                                                   Core (if applicable)        5.5.3

6.0 IP and Trial   6.3 Interactive                                                                  To provide instructions and define the operational instructions for the interactive
Supplies           Response Technology   IRT User Manual                                            response technology (IRT) for the user.                                               Core (if applicable)


                                                                                                    To document any agreements or significant discussions regarding trial supplies or
                                                                                                    containing relevant information about trial supplies, but not specifically listed in this
6.0 IP and Trial                                                                                    Reference Model. Types of correspondence may include, but not limited to: letters,
Supplies           6.4 Communications    Correspondence                                             memo, emails, telephone contacts.                                                         Core               8.3.11
6.0 IP and Trial                                                                                    Documents developed for the purpose of tracking activities during the course of the
Supplies           6.4 Communications    Tracking Document                                          trial.                                                                                    Recommended

                                                                                                    Agenda, presentation materials and other documentation generated during an
6.0 IP and Trial                                                                                    internal or external trial-related meeting which documents any agreements or
Supplies           6.4 Communications    Meeting Material                                           significant discussions regarding any IP and trial supplies for the trial.            Recommended
6.0 IP and Trial                                                                                    To document any decision or to clarify any information relating to the IP and trial
Supplies           6.4 Communications    Filenote                                                   supplies aspects of the trial.                                                        Core (if applicable)
                                                                                                                                                                                                    Core or
                                                                                                                                                                                               Recommended for ICH
     TMF Zone                 Section                    Artifact name           Alternate names                                       Definition / Purpose                                        inclusion   Code

                                                                                                     To clearly define the end-to-end process for the ongoing evaluation of safety;
                                                                                                     includes data to be collected, reporting objectives, and processes for a clinical trial.
                                                                                                     Plan may include but is not limited to associated documents for quality
                       7.1 Safety                                                                    management, safety database entry specifications and templates, and/or coding                                  2.2
7.0 Safety Reporting   Documentation        Safety Management Plan             Safety Reporting Plan guidelines.                                                                              Core                  5.16.1
                                                                                                                                                                                                                    5.16.1
                       7.1 Safety           Pharmacovigiliance Database Line                           To organize of a collection of data used for a variety of evaluative purposes (e.g.                          5.17.3
7.0 Safety Reporting   Documentation        Listing                            Periodic Line Listing   SAE case listings, database line listings, etc.).                                     Core                   8.3.17


                                                                               CIOMS Report            To assure notification by the sponsor of unexpected serious adverse drug reactions                           5.16.2
                                                                               Medwatch                and other safety information; submitted to regulatory authorities and IRBs/IECs.                             5.17
                                                                               IND Safety Report       Reports may include but are not limited to CIOMS, MedWatch, E2B Reports,                                     8.3.17-
7.0 Safety Reporting   7.2 Reports          Expedited Safety Report            SUSAR                   Analysis of Similar Events, cover letters, and/or country-specific reporting forms. Core (if applicable)     18


                                                                                                       To organize critical data around a serious adverse event, adverse event, and/or a
                                                                                                       laboratory abnormality as identified in the protocol. Reports may include but are not
                                                                                                       limited to specific regulatory forms and supporting data, reporter correspondence,
                                                                                                       associated note-to-files, source documentation, case logs, narratives, case                                  4.11
7.0 Safety Reporting   7.2 Reports          SAE Report                                                 unblinding forms, and/or safety database case printouts.                              Core (if applicable)   8.3.16


                                                                                                       To organize critical data around a pregnancy that occurred whilst either the male or
                                                                                                       the female subject was participating in a clinical trial. Reporting forms and
                                                                                                       supporting data collected for pregnancy cases. Reports may include but are not
                                                                                                       limited to specific regulatory forms, reporter correspondence, associated note-to-
                                                                                                       files, source documentation, case logs, case unblinding form, narratives, and/or                             4.11
7.0 Safety Reporting   7.2 Reports          Pregnancy Report                                           safety database case printouts.                                                      Core (if applicable)    8.3.16


                                                                                                       To organize critical data around a special event of interest, one that is of scientific
                                                                                                       and medical concern specific to the product or program. Usually requested by or
                                                                                                       submitted to Regulatory Agencies. Reports may include but are not limited to
                                                                                                       specific regulatory forms and supporting data, reporter correspondence, associated
                                                                               Medical Events of       note-to-files, source documentation, case logs, narratives, case unblinding forms,
7.0 Safety Reporting   7.2 Reports          Special Events of Interest         Interest                and/or safety database case printouts.                                                  Recommended


                                                                                                       To document any agreements or significant discussions regarding safety aspects of
                                                                                                       the trial or containing relevant information about safety aspects, but not specifically
                                                                                                       listed in this Reference Model. Types of correspondence may include, but not
7.0 Safety Reporting   7.3 Communications   Correspondence                                             limited to: letters, memo, emails, telephone contacts.                                  Core                 8.3.11


                                                                                                       To track information for the purposes of providing oversight of a process or specific
7.0 Safety Reporting   7.3 Communications   Tracking Document                                          data, case data in Safety Reporting zone (e.g. Intake logs).                          Recommended
                                                                                                                                                                                                      Core or
                                                                                                                                                                                                 Recommended for ICH
     TMF Zone                 Section                   Artifact name                 Alternate names                                   Definition / Purpose                                         inclusion   Code


                                                                                                        Agenda, presentation materials and other documentation generated during an
                                                                                                        internal or external trial-related meeting which documents any agreements or
7.0 Safety Reporting   7.3 Communications   Meeting Material                                            significant discussions regarding any safety aspects of the trial                       Recommended
                                                                                                        To document a specific situation with intention to provide additional information or
                                                                                                        clarification. Note-to-files should not be associated with specific Serious Adverse
7.0 Safety Reporting   7.3 Communications   Filenote                                                    Event cases.                                                                            Core (if applicable)


                                                                                                        To document recognition and approval by an authorized accrediting body applying
8.0 Centralized        8.1 Facility                                                                     known acceptable standards, that the facility is competent to perform required                                 8.2.12
Testing                Documentation        Certification or Accreditation          Qualifications      test(s), and support reliability of results; if applicable.                             Core                   8.3.7


                                                                                                        To document through use of control data that a non-accredited / non-certified
                                                                                                        laboratory can consistently and reproducibly report results that are reliable; may
                                                                                                        include but is not limited to reporting of results for a research test, antibody or
8.0 Centralized        8.1 Facility                                                                     pharmacokinetic testing that may be performed by an internal lab; required if                                  8.2.12
Testing                Documentation        Bioanalytical Documentation                                 certification or accreditation is not available.                                        Core (if applicable)   8.3.7
                                                                                                        To define acceptable limits (where 95% of the population that a facility serves will
8.0 Centralized        8.1 Facility                                                                     fall) for comparative interpretation that allow for medical decisions to be made; may                          8.2.11
Testing                Documentation        Normal Ranges                           Reference Ranges    be included in User Manual.                                                             Core                   8.3.6
8.0 Centralized        8.1 Facility                                                 Facility Manual     To outline the procedures to be followed in the collection, handling and shipping of
Testing                Documentation        User Manual                             Facility Handbook   samples; may not be available for local facilities.                                     Recommended            8.2.14
8.0 Centralized        8.1 Facility                                                                     To provide the necessary documentation required per country to allow for                                       8.2.15
Testing                Documentation        Supply Import Documentation                                 importation of supplies.                                                                Core (if applicable)   8.3.8
8.0 Centralized        8.1 Facility                                                                     To provide the necessary documentation required per country to allow for                                       8.2.15
Testing                Documentation        Sample Export Documentation                                 exportation of biological samples.                                                      Core (if applicable)   8.3.8
8.0 Centralized        8.1 Facility         Record of Retained Body Fluids /                            To document location and identification of samples being held for possible future
Testing                Documentation        Tissue Samples                                              (re)testing; to include destruction records, when and if this occurs.                   Core (if applicable)   8.3.25
                                                                                                        To verify that the Head of Facility is suitably qualified to lead and oversee the
8.0 Centralized        8.1 Facility                                                                     management and reporting of results; may be included with Certification /                                      8.2.12
Testing                Documentation        Head of Facility Curriculum Vitae                           Accreditation; may be found in the User Manual.                                         Recommended            8.3.7
                                                                                                        To confirm that two or more facilities can perform the same test / procedure and
8.0 Centralized        8.1 Facility                                                                     obtain consistent results; includes but may not be limited to phantom data for CT or                           8.2.12
Testing                Documentation        Interfacility Standardization Methods                       bioanalytical assay.                                                                 Core (if applicable)      8.3.7
                                                                                                        To capture critical information about the collection of a sample; may include but is
8.0 Centralized        8.2 Sample                                                                       not limited to subject ID, date and time of collection, etc; may be included in User
Testing                Documentation        Label                                   Specimen Label      Manual.                                                                                 Recommended
8.0 Centralized        8.2 Sample                                                   Specimen Shipment                                                                                                                  8.2.15
Testing                Documentation        Shipment Records                        Records             To provide relevant details for samples sent in any one shipment.                       Recommended            8.3.8
8.0 Centralized        8.2 Sample                                                   Specimen Storage
Testing                Documentation        Sample Storage Condition Log            Condition Log       To monitor and track sample storage under the appropriate conditions.                   Recommended            8.2.14
                                                                                                                                                                                                      Core or
                                                                                                                                                                                                 Recommended for ICH
     TMF Zone               Section                     Artifact name              Alternate names                                      Definition / Purpose                                         inclusion   Code
                                                                                                        To document any agreements or significant discussions with facilities or containing
                                                                                                        relevant information about the facilities, but not specifically listed in this Reference
8.0 Centralized                                                                                         Model. Types of correspondence may include, but not limited to: letters, memo,
Testing             8.3 Communications       Correspondence                                             emails, telephone contacts.                                                              Core                  8.3.11
8.0 Centralized                                                                                         To track information for the purposes of providing oversight of a process or specific
Testing             8.3 Communications       Tracking Document                                          data in centralized testing zone                                                         Recommended

                                                                                                        Agenda, presentation materials and other documentation generated during an
8.0 Centralized                                                                                         internal or external trial-related meeting which documents any agreements or
Testing             8.3 Communications       Meeting Material                                           significant discussions regarding any testing facilities aspects of the trial.          Recommended
8.0 Centralized                                                                                         To document any decision or to clarify any information relating to the testing facility
Testing             8.3 Communications       Filenote                                                   aspects of the trial.                                                                   Core (if applicable)


                                                                                                        To outline the operational techniques and activities undertaken within the quality
                                                                                 CRO,Sponsor, Joint     assurance system to verify that the requirements for quality of the trial-related
                    9.1 Third Party                                              Vendor Oversight       activities have been fulfilled. Relevant parts include but are not limited to an audit
9.0 Third parties   Oversight                Quality Plan                        Plan                   plan, monitoring plan, data verification steps.                                          Recommended           5.1
                                                                                 Documentation of
                                                                                 Decision to Utilize
                                                                                 Third Party
                                                                                 Qualification of       To confirm that a vendor meets all relevant criteria to fulfill a contractual obligation;
                    9.1 Third Party                                              Vendor                 may include a quality questionnaire, a visit report to qualify their capabilities, other
9.0 Third parties   Oversight                Evidence of Contractor Compliance   Audit Certificate      documents that support capabilities.                                                      Recommended
                                                                                                        To confirm by written legal agreement that key information between parties will be
                                                                                                        prevented from being inappropriately disclosed. May be included in another
9.0 Third parties   9.2 Third Party Set-up   Confidentiality Agreement                                  contractual agreement.                                                                   Core                  1.16
                                                                                 Vendor Selection
9.0 Third parties   9.2 Third Party Set-up   Contractor Selection                Documents              To identify how a vendor will be chosen and the criteria to be used in the process.      Recommended



                                                                                 Scope of Work
                                                                                 Project Work Order(s)
                                                                                 Change Order(s)
                                                                                 Financial Agreement
                                                                                 Contract
                                                                                 Service Agreement
                                                                                 Letter of Agreement   To document by a written dated signed agreement between two or more parties that
                                                                                 Authorization to      defines any arrangements on delegation and distribution of tasks and obligations;                               1.17
9.0 Third parties   9.2 Third Party Set-up   Contractual Agreement               Proceed               critical components include service description, responsibilities matrix and budget. Core                       8.2.6
                                                                                                                                                                                                        Core or
                                                                                                                                                                                                   Recommended for ICH
     TMF Zone               Section                     Artifact name              Alternate names                                       Definition / Purpose                                          inclusion   Code


                                                                                 Task Ownership
                                                                                 Matrix
                                                                                 Transfer of
                                                                                 Obligations            To identify range and distribution of tasks and responsibilities; may define internal
                                                                                 Transfer of Regulatory assignment and all external parties; covers GCP as well as business process; often                               5.2.2
9.0 Third parties   9.2 Third Party Set-up   Roles and Responsibilities Matrix   Obligation             part of the Contractual Agreement.                                                    Core                       5.7
                                                                                                        To document any agreements or significant discussions with Third Parties or
                                                                                                        containing relevant information about the Third Parties, but not specifically listed in
                                                                                                        this Reference Model. Types of correspondence may include, but not limited to:
9.0 Third parties   9.3 Communications       Correspondence                                             letters, memo, emails, telephone contacts.                                                Core                   8.3.11
                                                                                                        Agenda, presentation materials and other documentation generated during an
                                                                                                        internal or external trial-related meeting which documents any agreements or
9.0 Third parties   9.3 Communications       Meeting Material                                           significant discussions regarding any third parties.                                      Recommended
                                                                                                        To document any decision or to clarify any information relating to the any Third
9.0 Third parties   9.3 Communications       Filenote                                                   Parties utilized.                                                                         Core (if applicable)



                                                                                                        To identify the overall strategy for data management process: a compilation of
                                                                                 Data Management        documents that may include but are not limited to: Completion Guidelines,
10.0 Data           10.1 Data Management                                         Operational Plan       Database (build) Specification, Entry Guidelines, Database Testing; most if not all                              5.1
Management          Oversight            Data Management Plan                    Technology Plan        artifacts are listed in the Data Management zone.                                         Recommended            5.5
                                                                                                        To provide detailed instructions on how data points on each CRF are to be                                        1.46
10.0 Data                                                                                               completed; how to enter on paper AND if electronic data capture (EDC), how to                                    5.1
Management          10.2 Data Capture        CRF Completion Guidelines                                  enter data into the system.                                                               Core                   5.5



                                                                                                        To assign variable names and attributes to the fields on the CRF, and to link the
                                                                                                        variables to the tables within the database; may also be used as an aid for
10.0 Data                                                                                               database programming on how to structure the database; use for data extraction;                                  5.1
Management          10.2 Data Capture        Annotated CRF                                              may be generated at the time of regulatory submission.                                    Recommended            5.5


                                                                                                        A document which contains the available protocol-required information to be
                                                                                                        reported to the sponsor for each subject in the clinical trial; associated documents                             5.1
10.0 Data                                                                                               may include but is not limited to documentation of CRF corrections, subject diaries,                             5.5
Management          10.2 Data Capture        Completed CRFs (paper)                                     questionnaires, laboratory reports and other third-party specialty data.             Core                        8.3.14
                                                                                 Data Clarification
                                                                                 Forms
                                                                                 Data Correction                                                                                                                         4.9.3
10.0 Data                                                                        Forms                  A document to record approved corrections to the clinical trial database; includes                               5.5
Management          10.2 Data Capture        Documentation of CRF Corrections    Data Query Forms       self-evident corrections.                                                                 Core                   8.3.15
                                                                                                                                                                                              Core or
                                                                                                                                                                                         Recommended for ICH
    TMF Zone          Section                 Artifact name                  Alternate names                                      Definition / Purpose                                       inclusion   Code


                                                                                                  Final electronic copy to be kept at each site capturing the available protocol-
10.0 Data                                                                                         required information generated at the site reported via EDC to the sponsor for each
Management     10.2 Data Capture   Final Data (EDC)                                               subject in the clinical trial; for each subject in the trial for each site.         Core (if applicable)     8.3.14
                                                                                                  To provide a detailed framework to database designers on how a database is to be
                                                                           Database               built for paper and EDC; design requirements for the build of the database; for EDC                          1.46
10.0 Data                                                                  Programming            studies, user requirements may be included; also includes maintenance and                                    5.1
Management     10.3 Database       Database Specification                  Requirements           archiving guidelines.                                                               Core                     5.5
                                                                                                  To document import and export data specifications; includes but is not limited to
                                                                                                  diary, lab, IVRS, imaging; may include transfer from one group to another; may also
10.0 Data                                                                                         include data transfer from IVRS to EDC; any validation of the data sets would be                             5.1
Management     10.3 Database       External Data Transfer Specifications                          included.                                                                           Core (if applicable)     5.5

                                                                                                  To provide detailed instructions on how CRF data is to be entered into a database;
10.0 Data                                                                                         specific to a paper CRF trial (therefore, would not be required with an EDC trial),                          5.1
Management     10.3 Database       Data Entry Guidelines                                          including self-evident corrections and global conventions.                            Core (if applicable)   5.5


                                                                           Data integration
                                                                           Edit Check & Logic
                                                                           Check Specifications
                                                                           EDC Validation
                                                                           including Validation
                                                                           Test Plan
10.0 Data                                                                  Data Validation        To define edit checks and the process for edit check / validation testing, may                               5.1
Management     10.3 Database       Data Validation Plan                    Specification          include what test data is to be used.                                                  Core                  5.5
10.0 Data                                                                  Edit Check             To provide the code which satisfies the specification details in Data Validation Plan;                       5.1
Management     10.3 Database       Data Validation Programming             Programming            may include a reference to where the code resides.                                     Core                  5.5

                                                                           Edit Check Validation
10.0 Data                                                                  Data Validation       To provide evidence that the data validation programming has been done correctly                              5.1
Management     10.3 Database       Data Validation Testing                 Programming QC        and it accurately validates data as per the data validation plan.                Core                         5.5
                                                                           Database Release
                                                                           Approval              To provide documentation that all requirements of the database specification have
10.0 Data                                                                  Approval for Database been satisfied, and data entry can begin (go live); will also include confirmation that                       5.1
Management     10.3 Database       Approval for Database Activation        Go Live               data validation testing has been successfully completed.                                Core                  5.5
10.0 Data                                                                                        To document reconciliation and resolution of discrepancies between the safety and                             5.1
Management     10.3 Database       SAE Reconciliation                                            clinical databases has been completed.                                                  Core                  5.5
10.0 Data                                                                                        To document the process and tools used in medical coding; includes medical sign                               5.1
Management     10.3 Database       Medical Coding                                                off of coding; may include resolution discrepancies.                                    Core                  5.5

                                                                                                  To define the procedures for creating and implementing a Quality Control (QC) Plan
10.0 Data                                                                  QC/QA Database         to ensure that quality data is captured into a clinical database on an ongoing basis.                        5.1
Management     10.3 Database       Database QC / QA Plan & Results         Documentation          This would include any documentation of the results from the plan.                    Core                   5.5
                                                                                                                                                                                            Core or
                                                                                                                                                                                       Recommended for ICH
      TMF Zone            Section                   Artifact name            Alternate names                                   Definition / Purpose                                        inclusion   Code
10.0 Data                                                                                       Confirmation that all of the requirements for database release have been meet; may                           5.1
Management        10.3 Database         Database Lock Approval                                  include all unlock and re-lock documentation.                                      Core                      5.5
                                                                           EDC UAT Sign Off
10.0 Data                                                                  EDC Validation       To confirm that the data validation programming has been done correctly and it                               5.1
Management        10.3 Database         Data Validation Certification      Certification        accurately validates data as per the data validation plan.                            Core                   5.5
10.0 Data                                                                                                                                                                                                    5.1
Management        10.4 EDC Management EDC Account Creation Authorization                        To capture account management details.                                                Core (if applicable)   5.5


                                                                                                To document any agreements or significant discussions with data management or
                                                                                                containing relevant information about data management, but not specifically listed
10.0 Data                                                                                       in this Reference Model. Types of correspondence may include, but not limited to:
Management        10.5 Communications   Correspondence                                          letters, memo, emails, telephone contacts.                                            Core                   8.3.11
10.0 Data                                                                                       To track information for the purposes of providing oversight of a process or specific
Management        10.5 Communications   Tracking Document                                       data in the data management zone.                                                     Recommended

                                                                                                Agenda, presentation materials and other documentation generated during an
10.0 Data                                                                                       internal or external trial-related meeting which documents any agreements or
Management        10.5 Communications   Meeting Material                                        significant discussions regarding any data management aspects of the trial.           Recommended
10.0 Data                                                                                       To document any decision or to clarify any information relating to any aspects of
Management        10.5 Communications   Filenote                                                data management.                                                                      Core (if applicable)



                                                                                                To define, in detail, the statistical aspects of the trial design, the process of data
                                                                                                selection for all analyzes, the data items to be analyzed and all the procedures and
                  11.1 Statistics                                                               methods to be employed in the analysis of those data items as well as the planned
11.0 Statistics   Oversight             Statistical Analysis Plan                               presentation of those results (Tables, Listings and Figures (TLFs)).                   Core                  6.9
                                                                                                                                                                                                             1.48
                                                                                                To detail the randomization scheme and how the randomization will be carried out;                            5.1
11.0 Statistics   11.2 Randomization    Randomization Plan                                      this plan is then used to initiate programming.                                       Core                   5.5

                                                                                                To define the procedure which defines how subjects are randomized in a trial. This                           1.48
11.0 Statistics   11.2 Randomization    Randomization Procedure                                 could be by interactive response technology (IRT) or a manual process.             Core                      8.2.17
                                                                                                                                                                                                             6.4.8
                                                                           Randomization        To document the single source that holds the information on the assignment of                                8.2.18
11.0 Statistics   11.2 Randomization    Master Randomization List          Schedule             subjects to treatment or control groups.                                              Core                   8.4.3
                                                                                                Computer code and the process of writing the code to generate randomization                                  5.1
11.0 Statistics   11.2 Randomization    Randomization Programming                               number for treatment assignment.                                                      Core                   5.5
                                                                                                To verify that the randomization program generates the randomization number and
                                                                           Randomization Sign   treatment assignment correctly according to the randomization schema specified                               5.1
11.0 Statistics   11.2 Randomization    Randomization Validation           Off                  for the trial.                                                                  Core                         5.5
                                                                           Decoding Request
                                                                           Randomization        To document and authorize the release of the randomization code and allow the                                5.1
11.0 Statistics   11.2 Randomization    End of trial Unblinding            Release Request      trial data to be unblinded.                                                           Core                   5.5
                                                                                                                                                                                                    Core or
                                                                                                                                                                                               Recommended for ICH
      TMF Zone           Section                    Artifact name                 Alternate names                                       Definition / Purpose                                       inclusion   Code
                                                                                                        To define the programming logic required to transform the raw dataset to the                                 5.1
11.0 Statistics   11.3 Analysis         Data Definitions for Analysis Datasets                          analysis dataset; includes populations, etc; as outlined in the SAP.                  Core                   5.5
                                                                                                        To confirm the QC procedures planned for the analysis programs as well as the                                5.1
11.0 Statistics   11.3 Analysis         Analysis QC Documentation                                       actual output of the QC steps.                                                        Core                   5.5
                                                                                                                                                                                                                     5.1
11.0 Statistics   11.3 Analysis         Interim Analysis Raw Datasets                                   The export of raw data for interim analysis purposes.                                 Core (if applicable)   5.5
                                                                                                        The suite of programs designed to generate the interim analysis outputs as                                   5.1
11.0 Statistics   11.3 Analysis         Interim Analysis Programs                                       referenced in the SAP.                                                                Core (if applicable)   5.5
                                                                                                                                                                                                                     5.1
11.0 Statistics   11.3 Analysis         Interim Analysis Datasets                                       The datasets used for the interim analysis.                                           Core (if applicable)   5.5
                                                                                                        The Tables Listings and Figures produced from the interim analysis datasets;                                 5.1
11.0 Statistics   11.3 Analysis         Interim Analysis Output                                         includes Statistics approval.                                                         Core (if applicable)   5.5
                                                                                                                                                                                                                     5.1
11.0 Statistics   11.3 Analysis         Final Analysis Raw Datasets                                     The export of raw data for final analysis purposes.                                   Core                   5.5

                                                                                                        The suite of programs designed to generate the final analysis outputs as                                     5.1
11.0 Statistics   11.3 Analysis         Final Analysis Programs                                         referenced in the SAP.                                                                Core                   5.5
                                                                                                                                                                                                                     5.1
11.0 Statistics   11.3 Analysis         Final Analysis Datasets                                         The datasets used for the final analysis.                                             Core                   5.5
                                                                                                        The Tables, Listings and Figures produced from the final analysis datasets;                                  5.1
11.0 Statistics   11.3 Analysis         Final Analysis Output                                           includes Statistics approval.                                                         Core                   5.5
                                                                                Population Definition
                                                                                Criteria
                                                                                Protocol Violations                                                                                                                  5.1
                                        Subject Evaluability Criteria & Subject Deviations and          To define the criteria applied to each subject in the trial that will unambiguously                          5.5
11.0 Statistics   11.3 Analysis         Classification                          Exemptions              assign the subject to the populations established in the SAP.                         Core                   6.9.7
                                                                                                        To summarize the relevant statistical aspects of the interim analysis. May be                                5.1
11.0 Statistics   11.4 Report           Interim Statistical Report(s)                                   appended to the CSR.                                                                  Core (if applicable)   5.5
                                                                                                        To summarize the relevant statistical aspects of the final analysis. May be                                  5.1
11.0 Statistics   11.4 Report           Statistical Report                                              appended to the CSR.                                                                  Core                   5.5
                                                                                                        To document any agreements or significant discussions with statistics or containing
                                                                                                        relevant information about statistics, but not specifically listed in this Reference
                                                                                                        Model. Types of correspondence may include, but not limited to: letters, memo,
11.0 Statistics   11.5 Communications   Correspondence                                                  emails, telephone contacts.                                                           Core                   8.3.11
                                                                                                        To track information for the purposes of providing oversight of a process or specific
11.0 Statistics   11.5 Communications   Tracking Document                                               data in the statistics zone.                                                          Recommended

                                                                                                        Agenda, presentation materials and other documentation generated during an
                                                                                                        internal or external trial-related meeting which documents any agreements or
11.0 Statistics   11.5 Communications   Meeting Material                                                significant discussions regarding any statistical aspects of the trial.               Recommended
                                                                                                        To document any decision or to clarify any information relating to any aspects of
11.0 Statistics   11.5 Communications   Filenote                                                        statistics.                                                                           Core (if applicable)
                                         Used for metadata and to define paper             Inherited Metadata from Trial No
                                                      TMF format


 Artifact name
  in v1.0 EDM
   Reference     Study No / Trial No /   Trial Level                                Product /                      Trial      Route of     Artifact date/s as  Map to Current Company
     Model          Protocol No          Document       Country    Site No. / ID   Compound       Indication      Phase        Admin     defined by convention    Document Name         Location of Artifact

                          X                  X             X                           X               X            X            X                X



                          X                  X             X                           X               X            X            X                X



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                          X                  X                                         X               X            X            X                X

                          X                  X                                         X               X            X            X                X




Debarment
Certification             X                  X                          X              X               X            X            X                X
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  in v1.0 EDM
   Reference      Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
     Model           Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact


                           X                  X           X                           X            X          X         X                X

                           X                  X           X            X              X            X          X         X                X

                           X                  X                                       X            X          X         X                X

                           X                  X                                       X            X          X         X                X




                           X                  X           X                           X            X          X         X                X

                           X                  X           X                           X            X          X         X                X

                           X                  X           X                           X            X          X         X                X

Data Monitoring
Committee                  X                  X                                       X            X          X         X                X

Data Monitoring
Committee                  X                  X                                       X            X          X         X                X



Data Monitoring
Committee                  X                  X                                       X            X          X         X                X

                           X                  X                                       X            X          X         X                X




                           X                  X           X                           X            X          X         X                X

                           X                  X           X                           X            X          X         X                X



                           X                  X           X                           X            X          X         X                X

                           X                  X           X                           X            X          X         X                X
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     Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact



                          X                  X           X                           X            X          X         X                X




                          X                  X           X                           X            X          X         X                X




                          X                  X                                       X            X          X         X                X

Full Protocol
Protocol
Amendment                 X                  X                                       X            X          X         X                X

Synopsis                  X                  X                                       X            X          X         X                X



                          X                  X           X            X              X            X          X         X                X

Sample CRF                X                  X                                       X            X          X         X                X


                          X                  X                                       X            X          X         X                X

                          X                  X           X                           X            X          X         X                X

                          X                  X           X                           X            X          X         X                X

                          X                  X           X                           X            X          X         X                X
Informed
Consent                   X                  X           X            X              X            X          X         X                X

                          X                  X           X            X              X            X          X         X                X

                          X                  X           X                           X            X          X         X                X



                          X                  X           X            X              X            X          X         X                X
 Artifact name
  in v1.0 EDM
   Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
     Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact


                          X                  X           X            X              X            X          X         X                X



Legacy CSR
Report Body               X                  X                                       X            X          X         X                X

                          X                  X                                       X            X          X         X                X



                          X                  X                                       X            X          X         X                X



                          X                  X                                       X            X          X         X                X

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                          X                  X           X            X              X            X          X         X                X

                          X                  X           X            X              X            X          X         X                X




                          X                              X                           X            X          X         X                X
Letter of
Authorization             X                              X                           X            X          X         X                X



                          X                              X                           X            X          X         X                X

                          X                              X                           X            X          X         X                X

                          X                              X                           X            X          X         X                X
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  in v1.0 EDM
   Reference        Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
     Model             Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                             X                              X                           X            X          X         X                X

                             X                              X                           X            X          X         X                X

Notification of
Discontinuation
of Clinical Trial            X                              X                           X            X          X         X                X




                             X                  X           X                           X            X          X         X                X

                             X                  X           X            X              X            X          X         X                X




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                             X                              X            X              X            X          X         X                X
Artifact name
 in v1.0 EDM
  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                  X           X            X              X            X          X         X                X

                         X                  X           X            X              X            X          X         X                X

                         X                              X            X              X            X          X         X                X




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                         X                                           X              X            X          X         X                X




                         X                                           X              X            X          X         X                X

                         X                  X           X            X              X            X          X         X                X
 Artifact name
  in v1.0 EDM
   Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
     Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                          X                                           X              X            X          X         X                X

                          X                  X           X            X              X            X          X         X                X

                          X                                           X              X            X          X         X                X

Signature Page            X                                           X              X            X          X         X                X

Signature Page            X                                           X              X            X          X         X                X
Investigator
CVs                       X                                           X              X            X          X         X                X

Investigator
CVs                       X                                           X              X            X          X         X                X

                          X                                           X              X            X          X         X                X

                          X                                           X              X            X          X         X                X




                          X                                           X              X            X          X         X                X




Financial
Disclosure
Information               X                                           X              X            X          X         X                X

                          X                                           X              X            X          X         X                X




                          X                                           X              X            X          X         X                X
Artifact name
 in v1.0 EDM
  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact



                         X                                           X              X            X          X         X                X



                         X                                           X              X            X          X         X                X



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                         X                  X           X                           X            X          X         X                X



                         X                  X                        X              X            X          X         X                X

                         X                                           X              X            X          X         X                X
Artifact name
 in v1.0 EDM
  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                  X                        X              X            X          X         X                X




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   Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
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                          X                  X                        X              X            X          X         X                X



                          X                  X           X            X              X            X          X         X                X
Compliance
and/or Drug
Concentration
Data Listing              X                  X                        X              X            X          X         X                X

                          X                  X           X                           X            X          X         X                X



                          X                                           X              X            X          X         X                X



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Artifact name
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  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                  X           X                           X            X          X         X                X



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Artifact name
 in v1.0 EDM
  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                  X                                       X            X          X         X                X



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    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




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Artifact name
 in v1.0 EDM
  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                  X           X            X              X            X          X         X                X

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Artifact name
 in v1.0 EDM
  Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                  X           X                           X            X          X         X                X




                         X                  X           X                           X            X          X         X                X



                         X                  X           X                           X            X          X         X                X

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Data
Management
Plan                     X                  X                                       X            X          X         X                X



                         X                  X           X                           X            X          X         X                X




Annotated CRF            X                  X                                       X            X          X         X                X




                         X                                           X              X            X          X         X                X




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Artifact name
 in v1.0 EDM
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    Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact




                         X                                           X              X            X          X         X                X




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                         X                  X                                       X            X          X         X                X
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   Reference     Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
     Model          Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact


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Statistical
Analysis Plan             X                  X                                       X            X          X         X                X



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   Reference       Study No / Trial No /   Trial Level                              Product /                 Trial   Route of     Artifact date/s as  Map to Current Company
     Model            Protocol No          Document      Country   Site No. / ID   Compound     Indication   Phase     Admin     defined by convention    Document Name         Location of Artifact


                            X                  X                                       X            X          X         X                X

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Datasets                    X                  X                                       X            X          X         X                X
Program File for
Analysis
Dataset                     X                  X                                       X            X          X         X                X
Analysis
Datasets                    X                  X                                       X            X          X         X                X
Statistical
Output                      X                  X                                       X            X          X         X                X



Protocol
Deviation
Listing                     X                  X                                       X            X          X         X                X

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                            X                  X                                       X            X          X         X                X
                                                         The Trial Master File Reference Model
                                                                Version 1.0 4 June 2010

The Document and Records Management SIAC of the Drug Information Association (DIA), a recognized and highly respected professional association, is
supporting an initiative to create a Trial Master File (TMF) Reference Model.

Creation of the TMF Reference Model has involved more than 120 representatives, all DIA members, from 90 bio-pharmaceutical companies, contract
research organizations (CROs), consultancies, technical vendors, industry groups, healthcare, academia, non-for-profit / NGO and regulatory agencies. Each
contributor or stakeholder has provided their perspective on the standardized TMF taxonomy and metadata. The goal of the group was to create the TMF
Reference Model which can be used and adapted by any company. Therefore the attention of participants is drawn to the non-commercial nature of this forum.
Although it is acknowledged that the resulting reference model will ultimately need to integrate with commercially available products, this was by no means a
forum for promotion of products and companies.
The TMF Reference Model consists of standardized taxonomy and metadata and outlines the clear definition and organization of TMF content using standard
nomenclature. The TMF Reference Model output is non-binding in accordance with the DIA‟s scope and mission. This model is a reference for the industry
and should not be considered mandatory, but rather as an opportunity for standardization across the industry. The TMF Reference can be adapted to an
electronic or a paper TMF and does not endorse, nor by design, require, any specific technology for application.


Rationale for the creation of a model

The TMF contains those essential documents that individually and collectively permit the evaluation of the conduct of a trial and the quality of the data
produced. These documents serve to demonstrate the compliance of the investigator, sponsor, and monitor with the standards of GCP and with all applicable
regulatory requirements. (ICH Guideline for Good Clinical Practice, E6, Section 8).

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. Over the conduct of a
trial many functions contribute to the TMF, although oversight of the content is usually not one function‟s responsibility – resulting in a highly inefficient work
processes including but not limited to:

• All drug development companies and CROs expend considerable resources defining the content of the trial master file for each clinical trial. Consequently,
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.
• Records and information exchange between collaborating companies is extremely cumbersome, may prevent the transfer of a drug or joint venture.
• Regulators are challenged with varying terminology and file structures, creating inefficiency and a higher degree of variability during audits


Regulatory guidance, such as ICH E6 section 8, addresses only a sub-set of TMF documents. Documentation requirements for the set-up and maintenance of
quality systems, electronic systems, safety monitoring, and proof of an adequate and well-controlled trial, to name a few, exist in various regulations across
many countries or regions, but not in ICH E6. The goal of the TMF Reference Model is to provide a single, unified interpretation of the regulations via
document listing which would be accepted across the industry. It does not provide guidance in the process by which the document is the output.




                                                                                  Page 37 of 43
Organization of the model (underlined words are column headers in the attached model)
Defined in the model are document types, called artifacts, which one would expect to find in a TMF. It is important to note that progeny records such as artifact
approval/signature pages, amended artifacts or translation documentation are not called out uniquely since artifacts may have one or more progeny records
depending on trial requirements or a company‟s specific processes.


The artifacts are labeled either core, meaning it must be in the TMF as dictated by either the ICH Guidelines, regulations, or the TMF Reference Model group
(if applicable for the trial), or recommended meaning the artifact does not have to be produced but if it is created or collected, it is recommended to be in the
TMF. Since the industry often uses unique names, alternate names (as relevant) and descriptions are supplied for each artifact.
If the artifact is referenced in the ICH Guidelines, the reference is captured in the column “ICH Code”. Similarly, relationship to the sister Electronic Document
Management (EDM) Reference Model is captured in the column “EDM Reference Model” and if overlap is present, the artifact name EDM Reference Model,
version 1.0, is indicated.

The artifacts have been organized by:
Zone - where like artifacts are grouped together:
1 Trial Management
2 Central Trial Documents
3 Regulatory
4 IRB/IEC and Other Approvals
5 Site Management
6 Investigational Product (IP) and Trial Supplies
7 Safety Reporting
8 Centralized Testing
9 Third Parties
10 Data Management
11 Statistics

Section - organization of artifacts within each zone

Artifacts are created and exist at many levels such as trial, country, and site. An artifact, such as “Safety Management Plan” exists at only 1 of the levels, the
trial level. In contrast, the artifact “Informed Consent” can exist at all three. These levels define the paper format TMF




                                                                                  Page 38 of 43
Metadata

The TMF reference model also details basic metadata which can be used as a starting point for building TMF electronic document management processes.
This metadata model can be applicable in all electronic settings, from the straightforward file share to the complex enterprise system.

The trial number is captured on each of the artifacts in the TMF Reference Model. Since this model is designed to capture the unique set of documents
associated with a single trial, the trial number is attached to each artifact. Inherited metadata such as Product/Compound, Indication, Trial Phase, and Route is
also attached to each artifact and would be required to be entered only once, dependant upon system design.

Date format and convention for which date is captured on an artifact present on every artifact and has been left to those interpreting the reference model within
already defined processes. Artifacts would have country metadata associated with them if they were to be created for a specific country and a site number/ID if
created at the site level.


Next Steps

Immediate future objectives of the working group are to:
• obtain and implement a formal feedback mechanism for version 1.0, and
• continue to extend/improve the model as needed to enable innovation and process improvement within the industry, and
• determine a sustainable method and format for dissemination of the model

To become involved with the continued enhancement and maintenance of this TMF Reference Model, contact the DIA Document and Records Management
SIAC, located on the DIA website or join the LinkedIn Group called “TMF Reference Model”.




                                                                                Page 39 of 43
           TMF Reference Model Feedback Form                                                                 Version 1.0                   4-Jun-10

                    Name                                                                Tel no.

              Company                                                                    Email


 Description of Use

General Instructions for providing feedback on the TMF Reference Model (version 1.0) are as follows:
-All comments to be detailed below. Do not unlock reference model sheet and add comments within table. Comments submitted in this manner will not be considered.
-Capture comments in "General" section or by zone for artifact or it's associated data below. Copy row with artifact and add comments in applicable cell or comment column.
-Add additional rows if comments for >3 artifacts in a zone are submitted. Please note any artifacts that are thought to be missing from the model.
-Save, appending your name to the document name, and submit this entire workbook via email to "DIA_TMF_Reference_Model@comcast.net"

GENERAL Comments:




                                                                                                                                            Core or
                                                                                                                                       Recommended for
        TMF Zone           Section              Artifact name               Alternate names               Definition / Purpose             inclusion       ICH Code
1.0 Trial Management
1.0 Trial Management

2.0 Central Trial
Documents
2.0 Central Trial
Documents
2.0 Central Trial
Documents

3.0 Regulatory
3.0 Regulatory
3.0 Regulatory

4.0 IRB/IEC and other
Approvals
                                                                                                    Core or
                                                                                               Recommended for
        TMF Zone            Section   Artifact name   Alternate names   Definition / Purpose       inclusion     ICH Code
4.0 IRB/IEC and other
Approvals
4.0 IRB/IEC and other
Approvals

5.0 Site Management
5.0 Site Management
5.0 Site Management

6.0 IP and Trial Supplies
6.0 IP and Trial Supplies
6.0 IP and Trial Supplies

7.0 Safety Reporting
7.0 Safety Reporting
7.0 Safety Reporting

8.0 Centralized Testing
8.0 Centralized Testing
8.0 Centralized Testing

9.0 Third parties (if
applicable)
9.0 Third parties (if
applicable)
9.0 Third parties (if
applicable)

10.0 Data Management
10.0 Data Management
10.0 Data Management

11.0 Statistics
11.0 Statistics
11.0 Statistics
d.
column.




                                             Used for metadata and to define paper              Inherited Metadata from Trial No
                                                          TMF format


                                Study No /                                                                                                    Artifact date/s as
       Artifact name in v1.0    Trial No /   Trial Level                                Product /                                  Route of      defined by         General
      EDM Reference Model      Protocol No   Document       Country    Site No. / ID   Compound       Indication   Trial Phase      Admin        convention        Comments
                          Study No /                                                                                              Artifact date/s as
 Artifact name in v1.0    Trial No /   Trial Level                              Product /                              Route of      defined by         General
EDM Reference Model      Protocol No   Document      Country   Site No. / ID   Compound     Indication   Trial Phase    Admin        convention        Comments

								
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