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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
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)
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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)
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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)
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
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
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)
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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
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
Core or
Recommended for ICH
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion Code
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 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 X X X X X X
X X X X X X X
Debarment Certification X X X X X X X X
X X X X X X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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
X X X X X X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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
X X X X X X X X X
Legacy CSR
Report Body X X X X X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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
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
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
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 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 X X X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 X
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
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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
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 X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 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
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 X X X X X X
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
X X X X X X X X
X X X X X X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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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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
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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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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 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 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
X X X X X X X X X
X X X X X X X X X
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
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 X X X
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Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
X X X X X X X X
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Data Management Plan X X X X X X X
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Annotated 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
Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
X X X X X X X
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Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
X X X X X X X X
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Statistical Analysis Plan X X X X X X X
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Artifact name in v1.0 Study No / Trial No / Trial Level Product / Trial Route of Artifact date/s as Map to Current Company Document
EDM Reference Model Protocol No Document Country Site No. / ID Compound Indication Phase Admin defined by convention Name
X X X X X X X
X X X X X X X
X X X X X X X
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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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 35 of 41
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 36 of 41
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 37 of 41
TMF Reference Model Feedback Form Version 1.0 4-Jun-10
Name Tel no.
Company Email
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 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.
-Save, appending your name to the document name, and submit this entire workbook via email to "DIA TMF Reference Model@comcast.net"
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
4.0 IRB/IEC and
other Approvals
4.0 IRB/IEC and
other Approvals
5.0 Site Management
Core or
Recommended for
TMF Zone Section Artifact name Alternate names Definition / Purpose inclusion ICH Code
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
dered.
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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