Clinical scenarios and product decisions

How to review these scenarios

For each scenario, a TMF product reviewer should confirm that the model identifies the responsible person, preserves prior truth, refuses unsafe shortcuts, and leaves enough evidence for a future study team or inspector to understand what happened.

1. Protocol amendment changes expected content

Protocol Amendment 2 adds a new assessment and requires country approvals, revised participant materials, site communication, training, and revised data-management evidence.

Expected behaviour:

1. Approve a new Filing Plan Revision with its relationship to the protocol amendment.
2. Revise or add Document Expectations for the affected evidence.
3. Generate Filing Slots for applicable countries and sites from actual amendment submission, approval, distribution, training, and implementation facts.
4. Preserve the slots and rules that governed the original protocol period.
5. Match each exact final Document Version to the appropriate Filing Slot.
6. Show sites that have not yet approved or implemented the amendment without treating their records as missing prematurely.

2. Country withdrawal before approval

A planned country is withdrawn before regulatory authorization.

Expected behaviour:

• Do not delete all country Filing Slots.
• Decide which pre-withdrawal records remain essential to explain selection, submission, correspondence, decisions, and withdrawal.
• Mark only genuinely inapplicable future slots Not Required, with decision-maker, date, and rationale.
• Create or retain withdrawal and closeout expectations where applicable.

3. Site added after study start

A new site joins after two protocol amendments are already effective.

Expected behaviour:

• Generate the site’s Filing Slots from the Filing Plan Revision governing its start.
• Expect the correct current documents plus any earlier evidence needed to show the site’s selection and activation.
• Do not create irrelevant historical slots merely because they existed for earlier sites.
• Retain which document versions the site received, acknowledged, approved, and implemented.

4. Monitoring visit canceled

A monitoring visit was planned but canceled before it occurred.

Expected behaviour:

• Preserve the planned event and cancellation evidence.
• Do not expect a completed-visit report when the Document Expectation is triggered only by a completed visit.
• If a cancellation record or rescheduling decision is essential, create the appropriate Filing Slot.
• Prevent a false missing-report timeliness failure.

5. One document satisfies two needs

One signed committee record contains both membership confirmation and the meeting decision.

Expected behaviour:

• Create one TMF Document and one exact Document Version.
• Match it explicitly to both Filing Slots.
• Record why the combined evidence is sufficient for each.
• Count each slot once without duplicating content.
• Reassess both matches if a later version changes only one part of the evidence.

6. Same file uploaded twice

The same PDF arrives through email and bulk transfer with different filenames.

Expected behaviour:

• Detect the identical checksum and open a Duplicate Assessment.
• Confirm whether both intake origins or filing contexts have evidential value.
• Retain one authoritative Document Version when appropriate and relate or reject the duplicate intake.
• Preserve both receipt histories.
• Do not count both toward one Filing Slot.

7. Identical content valid for multiple sites

A central laboratory manual applies unchanged to 40 sites.

Expected behaviour:

• Avoid creating 40 uncontrolled copies of the content.
• Retain one authoritative TMF Document where the filing plan permits it.
• Represent site applicability or controlled cross-reference separately from site distribution and acknowledgement.
• Do not claim a site received or implemented the manual merely because the central record exists.

8. Sites implement an amendment on different dates

The amended protocol is final centrally, but local approvals and implementation dates vary.

Expected behaviour:

• Preserve all protocol Document Versions and the central effective decision.
• Retain country and site approval, receipt, acknowledgement, training, and implementation evidence separately.
• Determine the applicable version for conduct at a site on a given date.
• Refuse a single study-wide implementation date if it is not true.

9. Misfile discovered after finalization

A final ethics approval is filed under the wrong country.

Expected behaviour:

• Retain the final Document Version unchanged.
• Record the finding or approved self-evident correction.
• End the incorrect filing placement and create the correct one.
• Re-evaluate Filing Slot matches and measure snapshots prospectively.
• Preserve the original country value, corrected value, actor, time, reason, and verification.

10. Incomplete certified copy

A paper approval was scanned, but the reverse side containing conditions is missing.

Expected behaviour:

• Fail certified-copy fidelity and document-level QC.
• Prevent finalization and destruction of the original.
• Obtain a complete scan as another Document Version or component set.
• Retain the failed copy, finding, correction, and verification as required by procedure.

11. Dynamic record stored only as PDF

A calculation spreadsheet is rendered as PDF, but formulas and filters are necessary to understand the result.

Expected behaviour:

• Treat the PDF as a rendition, not a complete replacement source.
• Retain the dynamic source with the metadata and environment information required for use.
• Record the relationship and fidelity limitations.
• Refuse archive approval if the authoritative dynamic evidence will become inaccessible.

12. Email decision lacks its attachment

An email documents a study decision but refers to an attached analysis that was not retained.

Expected behaviour:

• Identify the email record as incomplete.
• Preserve the relevant conversation strand without unnecessary unrelated email.
• Obtain and associate the exact attachment where possible.
• Record a finding or approved exception if the attachment cannot be recovered.

13. Late filing after a milestone

A required report is finalized and filed 20 days after its allowed filing period.

Expected behaviour:

• The Filing Slot becomes fulfilled when the acceptable version is matched.
• Content completeness is restored.
• The timeliness failure and original due calculation remain.
• Recording the milestone actual date or refiling the report does not reset the clock.

14. Not Required used to improve a metric

A study team member attempts to mark overdue Filing Slots Not Required without supporting trial facts.

Expected behaviour:

• Refuse the decision unless the user has authority and supplies a rationale and evidence.
• Record the previous status and attempted or completed change.
• Route material or retrospective applicability changes for independent review.
• Keep pending decisions visible in measure detail.

15. Unblinded record exposed to blinded users

An unblinded safety record is classified into a location readable by the blinded study team.

Expected behaviour:

• Prevent or immediately contain access.
• Record an access/privacy quality finding and affected users.
• Correct the filing placement or permission without altering the Document Version.
• Assess whether disclosure occurred and preserve follow-up decisions.

16. Direct participant identifiers reach the sponsor

A site uploads signed consent forms containing direct identifiers into the sponsor eTMF.

Expected behaviour:

• Quarantine access and prevent ordinary sponsor filing.
• Notify the responsible privacy and investigator/institution roles under approved procedure.
• Return, securely remove, or otherwise resolve the content while preserving necessary incident evidence.
• Retain the appropriate Filing Slot outcome without implying that the sponsor owns the site record.

17. Service provider closes

A service provider holding monitoring records and audit history ceases operation during the study.

Expected behaviour:

• Invoke the continuity and transfer arrangements in the Filing Plan Revision.
• Inventory records, versions, metadata, audit evidence, and open work held by the provider.
• Transfer with a manifest and recipient verification.
• Record gaps, corrections, custody history, and sponsor oversight.
• Prevent a bare file transfer from being treated as complete if context or history is missing.

18. External location fails at closeout

The filing plan points to a training system that is no longer accessible.

Expected behaviour:

• Fail retrieval testing and raise a quality finding.
• Determine whether authoritative records can be recovered with their required metadata and history.
• Reconcile recovered content to Filing Slots.
• Record an exception and impact assessment for unrecoverable evidence.
• Refuse archive approval while the gap is concealed or unowned.

19. Reference taxonomy changes mid-study

A new Reference Model Release splits one artifact into two.

Expected behaviour:

• Keep the current Filing Plan Revision unchanged until the organization deliberately evaluates adoption.
• If adopted, approve a new Filing Plan Revision with mappings and an effective date.
• State whether existing Filing Slots remain under the old interpretation or are migrated.
• Preserve historical measures and filing placements under their original taxonomy.

20. Inspection begins during active filing

The authority requests records through 31 July while the study continues.

Expected behaviour:

• Create a defined disclosed record set at the agreed cut-off.
• Continue controlled ordinary filing in the active TMF.
• Provide later relevant records as traceable supplements.
• Prevent silent replacement of versions already disclosed.
• Keep inspection access read-only, scoped, time-limited, and auditable.

21. Closeout milestone completed with gaps

The study lead enters the actual closeout date while five required Filing Slots remain unresolved.

Expected behaviour:

• Preserve the actual operational date.
• Keep all five Filing Slots missing, rejected, or excepted as their evidence shows.
• Refuse automatic 100% completeness.
• Require owners, due dates, and accepted operational exceptions.
• Prevent archive approval until reconciliation reaches an approved conclusion.

22. Archive retrieval test fails

Five years after archive, several files cannot be opened.

Expected behaviour:

• Record the failed test and affected exact Document Versions.
• Open a quality finding and begin approved recovery or migration.
• Verify recovered content against checksums, metadata, and relationships.
• Preserve the failure, recovery, and verification history.
• Assess whether authorities or responsible parties require notification.

23. Ownership changes after acquisition

The sponsor transfers archive ownership to an acquiring organization.

Expected behaviour:

• Identify exact archive packages, obligations, holds, and current custodian.
• Approve the new owner and transfer arrangement.
• Transfer with manifest, checksums, and recipient verification.
• Record the effective ownership change without erasing prior ownership.
• Maintain availability throughout the transfer.

24. Retention expires but a hold remains

The scheduled retention period ends while a regulatory investigation is open.

Expected behaviour:

• Prevent destruction for the held scope.
• Show the hold authority, reason, review date, and responsible owner.
• Permit destruction only after authorized release and a fresh eligibility check.
• Preserve the destruction decision and certificate when destruction eventually occurs.

25. Repeated visits are hidden in one expected count

A study has ten completed monitoring visits. Nine reports are filed, but a single expected item shows “9 of 10” without identifying the missing visit.

Expected behaviour:

• Generate one Filing Slot for each completed visit.
• Identify the exact missing visit, site, trigger date, owner, and due date.
• Match each report’s exact Document Version to its own slot.
• Refuse a quantity-only result that cannot show which occurrence is missing.

26. Classification changes after QC

A Document Version passes QC as general correspondence and is later recognized as a regulatory decision.

Expected behaviour:

• Preserve the classification and metadata revisions used in the completed QC Round.
• Create a new classification revision with reason, reviewer, and effective date.
• Reassess filing placement, Filing Slot matches, access, and required QC criteria.
• Open another QC Round against the same content and new classification when required.
• Do not make the prior QC result appear to cover the corrected classification.

27. QC rework occurs three times

A monitoring report fails first for a missing signature, then for an incorrect visit date, and passes on the third attempt.

Expected behaviour:

• Keep one QC Request with three ordered QC Rounds.
• Pin the exact Document Version, classification revision, metadata revision, and criterion results for each round.
• Link each failed criterion to its Quality Finding and correction.
• Finalize and file only after the required round is accepted.
• Preserve the rework duration and original timeliness facts.

28. Replacement filing plan splits an expectation

A new Filing Plan Revision replaces one combined approval expectation with separate regulatory and ethics approval expectations.

Expected behaviour:

• Reconcile the old and new expectations as a split before the new revision becomes effective.
• Give every open Filing Slot an explicit treatment.
• Preserve already fulfilled historical slots and measures under the prior revision.
• Generate future slots under the new rules without double counting existing evidence.

29. Exception is approved for a missing historical record

A service provider cannot recover one historical training record, and reconstruction from other evidence is adequate under an approved quality decision.

Expected behaviour:

• Keep the Filing Slot missing and any Quality Finding open or historically visible.
• Create a separate Exception Decision identifying the unmet requirement, impact, controls, approvers, evidence, and permanent or time-limited treatment.
• Show the exception separately in completeness, readiness, and archive reconciliation.
• Refuse to relabel the record Not Required when it was genuinely required.

30. External record reference points only to a current screen

The filing plan says validation evidence is held in another system, but the reference opens only the current record and cannot identify the version that supported the study three years earlier.

Expected behaviour:

• Refuse the reference as fulfilment of its Filing Slot.
• Require an exact external Document Version, stable identifier, responsible owner, retention, metadata, audit-history availability, and successful retrieval evidence.
• Recover or transfer the historical version and reassess QC.
• Record the accessibility failure and archive impact.

31. Two protocol versions are current in different sites

Protocol Amendment 3 is active at Site US-101 while Site DE-014 still conducts under Amendment 2 pending local approval.

Expected behaviour:

• Keep one stable TMF Document identity and both exact Document Versions.
• Derive the current Document Version separately for each filing/implementation scope and as-of time.
• Show “varies by scope” rather than selecting one study-wide current version.
• Preserve the classification revision, metadata revision, Active Filing Placement, and supersession decision supporting each result.
• Refuse to choose the latest version number or upload time as the universal current version.

32. Active placement is corrected after a metadata revision

A final document was filed with Site FR-012 metadata and later confirmed to belong to Site FR-021.

Expected behaviour:

• Preserve the stable TMF Document and exact Document Version.
• Create the corrected metadata revision.
• End the original Filing Placement with its identifier, end time, reason, and decision-maker.
• Create and activate a new placement pinned to the same Document Version, current classification revision, corrected metadata revision, and exact Filing Plan Revision.
• Preserve both placement identities; never edit or reactivate the ended placement.

33. A missing slot has a temporary exception

A required approval letter is overdue and unavailable, but an authorized temporary Exception Decision allows a milestone review to proceed under stated controls.

Expected behaviour:

• Keep the Filing Slot status Due — no acceptable match.
• Keep the Missing/Overdue deficiency visible.
• Show the approved Exception Decision separately with expiry, controls, owner, and follow-up.
• When the letter is later filed, change the slot to Fulfilled while preserving Late and the historical Exception Decision.
• Never call the slot Overfilled if several candidate versions arrive; reconcile the additional evidence.

Product decisions requiring review

ID	Decision	Why it matters
ETMF-D01	Which organization role may approve a Filing Plan Revision?	Approval establishes responsibilities and rules for regulated records.
ETMF-D02	Which study changes require a new revision versus a recorded no-impact decision?	Over-revision creates noise; under-revision loses historical explanation.
ETMF-D03	Which filing levels beyond Study, Country, and Site are first-class?	Person, Organization, Product, Committee, and Event scopes change expectation generation and access.
ETMF-D04	Which roles may approve one Document Version for use in several Filing Slots?	The permitted number of relationships is fixed, but review authority for combined evidence remains a product decision.
ETMF-D05	Which evidence compositions may form one Filing Slot’s accepted evidence set?	A slot has one accepted set, but permitted multi-version compositions require clinical rules.
ETMF-D06	Which metadata corrections qualify as self-evident?	Determines when streamlined correction is safe after finalization.
ETMF-D07	Which finding types and severities block finalization, milestone acceptance, readiness, or archive?	These are different clinical decisions and should not share one blanket rule.
ETMF-D08	What independence is required between contributor, classifier, QC reviewer, approver, and verifier?	Controls conflict of interest without creating unnecessary handoffs.
ETMF-D09	Which automatic classification or matching decisions may proceed without human confirmation?	Automation must not obscure accountability or uncertainty.
ETMF-D10	How is timeliness defined by artifact—start event, endpoint, calendar, pauses, and threshold?	A single global number is clinically misleading.
ETMF-D11	How are repeating, event-driven, and expiring expectations forecast and reconciled?	Determines whether missing and additional-evidence measures are truthful.
ETMF-D12	How are centrally applicable documents distinguished from site distribution and acknowledgement?	Existence, applicability, receipt, and implementation are different facts.
ETMF-D13	Which records may remain in external systems through archive, and what retrieval evidence is required?	Determines whether the TMF remains complete and directly accessible.
ETMF-D14	How are sponsor and investigator portions represented without implying sponsor ownership or access?	Necessary for participant privacy and investigator control.
ETMF-D15	What is included in inspection export by default: audit history, superseded versions, renditions, and external references?	The disclosed set must be understandable and reproducible.
ETMF-D16	What conditions permit Ready with Declared Limitations?	Prevents readiness from becoming an optimistic label.
ETMF-D17	Who approves archive exceptions and who may accept custody?	Archive gaps and transfers have long-lived regulatory impact.
ETMF-D18	How are overlapping jurisdictional and contractual retention rules resolved?	Destruction eligibility depends on the latest applicable obligation.
ETMF-D19	What archive test frequency and sample are required for different risk classes?	Long-term readability must be demonstrated proportionately.
ETMF-D20	What evidence is retained when an intake item is rejected or securely removed for privacy?	The incident must remain explainable without retaining prohibited content unnecessarily.
ETMF-D21	Which classification and metadata changes require another QC Round?	The exact reviewed revisions are preserved, but risk-based re-review rules require agreement.
ETMF-D22	Which filing-plan reconciliation items block the replacement revision from taking effect?	Every item needs treatment; the business must define which unresolved treatments are blocking.
ETMF-D23	Which exception types require Quality, Privacy, Medical, or sponsor-level approval?	Approval authority should reflect the impact of the unmet requirement.
ETMF-D24	What integrity evidence is acceptable when an external system cannot supply a checksum?	External version identity must be defensible without inventing false precision.

These decisions should be answered in TMF and clinical-operations language before implementation choices are made.