Trial Master File

Zones, documents, quality control, metrics, site pages and requests, expiry reminders, inbox, records from YouEDC Capture, site copies at close-out.

The Trial Master File (TMF) is the evidence of how a study was run: an inspector uses it to reconstruct who did what and when. In YouEDC the TMF lives inside a project (the “Trial Master File” item of the project menu) and follows the 11 zones of the CDISC TMF Reference Model.

A document's path: uploaded by hand or captured from a portal report through the inbox, then quality control, then filed and counted in the metrics.

What is expected

The portal knows which documents a study needs at each stage: start-up, conduct, close-out. Site documents (principal investigator CV, GCP certificate, delegation log, local ethics approval) are expected for every site. When a document does not apply, mark it not applicable with the reason: it then counts as complete.

Versions and quality control

• Every file is kept with its SHA-256 checksum. A new file of the same document becomes the next version; older ones are never deleted.
• Critical documents (protocol, approvals, investigators' CV and GCP, UAT, database lock) always go through QC; the others by a sample the project administrator sets.
• QC is done by the project administrator or a data manager, never by the person who uploaded the version. Returning a document needs a note.
• CV, GCP certificates, licences and certificates get a validity date (CV 2 years, GCP 3 years by default); the overview shows what expires within 90 days.

Metrics

• Completeness: expected documents that are filed or not applicable.
• Filed on time: documents filed within N days of their own date (30 by default).
• QC first time right: documents accepted without being returned.

Inbox: the portal's own reports

When someone downloads a portal report inside the project (audit trail, query report, SAE reconciliation, data review), a copy lands in the TMF inbox. A data manager files it into the right zone (usually zone 10, Data management) or dismisses it. The TMF fills up as a by-product of the work instead of by moving files around.

Site page and requests

The Overview has a “By site” table: completeness, what is missing, expired, being checked and requested. Click a site to open its page: every document the site keeps, with its state, dates and the “File it” and “Ask the site” buttons. Investigators see only their sites; for them it is the list of what their site still owes.

A request closes by itself when the site uploads the document. Expiry reminders come 30 days before and again on expiry.

• The project administrator, a data manager or a monitor can ask for a document, with a note (“the signed version, please”) and a date.
• The site's investigators get an e-mail (they can switch it off in the profile) and see the request at the top of the TMF Overview.
• Example: site 03's GCP certificate has expired. The monitor clicks “ask the site”, writes “renewed certificate”, sets a date a week ahead. The doctor uploads the new file as a new version, the request closes, the document goes to QC.

Expiry reminders

30 days before a CV, GCP certificate, licence or laboratory accreditation expires, the portal writes to the people who file that site's documents, and once more on the day it expires. Each e-mail goes once; a new version of the document stops the reminders.

Delegation log

A site's page has the tabs Documents, Delegation log, Read and confirm and the Site file (ZIP) button. On top is the site's inspection readiness: five things an inspector checks first (the site's documents, a signed log, work in the EDC matching the delegation, everyone's CV and GCP, reading of the current documents).

• Everyone who does study tasks at the site goes on the log: an investigator with an account is chosen from the list, a person without one (a nurse, a pharmacist) is entered by name. A line has the position, the tasks from a standard list and the dates from and until.
• The site's investigators, the project administrator, data managers and monitors keep the log. A change needs a reason and goes to the audit trail.
• The principal investigator (a line with the task “Principal investigator” and an account) signs the log by entering the password again. The signed PDF is filed in the TMF by itself as a new version of the site's delegation log and goes through quality control. A line changed after the signature waits for the next one.

Cross-check of the log with the EDC and the qualification

The block “What an inspector would find” is counted again every time the page opens:

• an investigator works at the site in the portal but is not on the log; the delegation ended but the access to the site stayed;
• data entry, query answers, consents and enrolments for the site's patients (from the YouEDC Capture audit trail) done without a line on the log, outside the dates of the delegation or without the task;
• a person has no CV or GCP certificate, or it has expired or expires within 30 days. A person's CV and GCP are filed as “Site staff CV” and “Site staff GCP training certificate” with the person chosen from the log; for the principal investigator the documents “Principal investigator CV” and “GCP training certificate” count too.

Reading, and the site file in one download

When a new version of the protocol, an amendment, the investigator's brochure, the consent form or the CRF completion guidelines is filed in the TMF (after QC, or at once when no QC is needed), everyone currently on the sites' logs must confirm they read it. A person with an account gets an e-mail and presses “I have read it”; for someone without an account the site records where the signed paper sheet is kept. Confirmations are never taken back.

Site file (ZIP) puts together the site file as it is now: sections (protocol and brochure, approvals, staff, training, monitoring, product, laboratory, data), the current version of every document, the delegation log with the qualification check, the reading record, the inspection readiness and the index 00_INDEX.csv with the SHA-256 of every file. The download goes to the audit trail. The sponsor (Viewer role) cannot download it.

What YouEDC Capture puts in the TMF by itself

Records of the study's milestones reach the Inbox without manual work.

• Go-live: a record that the database was approved for use (who launched it and when) and the eCRF design at that moment in CDISC ODM 1.3.2.
• Database lock and unlock: a record with the date, the person and the reason.
• Site close-out: the site's data with its audit trail in the site's package; the receipt is filed by itself.

Copies of the data for the sites

At close-out every site must get a copy of its own data: the sponsor must not be the only one who holds it. On the “Site copies” tab the portal prepares the package, you record how it was handed over, the site confirms receipt and the receipt is filed in the TMF. In a YouEDC Capture study the package also holds the site's data (Excel and CDISC ODM 1.3.2) and its patients' audit trail, in the folder ecrf/.

Export

“Export” builds a ZIP with folders by zone and a manifest.csv with the metadata and SHA-256 of every file, ready for the sponsor's eTMF.

Example

To see everything on ready-made data, open the example: study DEMO-TMF in conduct, three sites, with typical problems (missing documents, an expired GCP certificate, a CV returned by QC, late filing).

Open the example

This is a prototype. Files are kept in the portal's database; long-term TMF retention (25 years in the EU and the UK) needs a separate archive and validation. Zone numbers follow the TMF Reference Model; the list of document types is ours and will be checked against the official CDISC table.