Research Roadmap

To ensure transparency and traceability in research subject to the WMO, researchers are required to meticulously maintain all essential study records created during the setup and conduct of a study. 
 According to GCP-guidelines, essential study records are those that enable the evaluation of both the conduct of the study and the quality of the data produced. These records serve to demonstrate compliance with the study protocol, GCP-standards, and applicable laws and regulations, thereby allowing for complete reconstruction of the study. Furthermore, they facilitate effective monitoring, audits and regulatory inspections, while safeguarding the rights, safety and well-being of participants. 

GCT SOP 03 Management and archiving of essential documents describes the responsibilities and procedures for the management of essential study records at Amsterdam UMC, in accordance with applicable laws and regulations.

Study files: TMF, ISF and IPSF

Essential study records must be maintained in a study file. This study file must be identifiable and accessible to authorized research staff, monitors, auditors, and inspectors. The essential study records must be complete, up to date, accurate, legible and traceable throughout the study. 

A distinction is made between three types of study files:

1. Trial Master File (TMF): the study file maintained by the sponsor (coordinating principal investigator);
2. Investigator Site File (ISF): the study file maintained by the local principal investigator at each participating center; 
3. Investigator Participant Site File (IPSF): a separate section of the TMF/ISF containing essential study records with directly identifiable (personal) data. Because these traceable records are subject to privacy legislation (GDPR/AVG), access must be restricted to the principal investigator and/or their delegate. Examples include the subject identification list and signed informed consent forms.

Amsterdam UMC has established mandatory TMF/ISF/IPSF indexes for different types of research to structure the study file and offer an overview of the minimum required records. 

When Amsterdam UMC acts as both the sponsor and a participating center, the TMF and ISF are preferably combined to prevent duplicate administration. 

• Index combined TMF&ISF: investigational medicinal product studies subject to the CTR*
• Index combined TMF&ISF: medical device studies subject to the MDR*
• Index combined TMF&ISF: WMO studies not subject to the CTR or MDR*
• Index combined TMF&ISF: nonWMO studies
• Index investigator site file (ISF): investigator medicinal product studies subject to the CTR*
• Index Investigator site file (ISF): medical device studies subject to MDR*
• Index investigator site file (ISF): WMO studies not subject to the CTR or MDR*
• Index investigator participant site file (IPSF)*

Organizing the study file

The foundation of the study file consists of the documents approved by the review committee (MREC or CCMO). During the study, additional (conduct-related) documents are added to the TMF/ISF/IPSF. These may include signed informed consent forms, training logs, participant logs, as well as records completed by different departments and/or (external) vendors.

Amsterdam UMC encourages to maintain the TMF/ISF digitally. Two platforms are supported: 

• Departmental network drives, provided that access is appropriately controlled and limited to authorized research staff;
• Research Manager (Studymanagement module, CTMS), a manual is available under Documents & Templates. 

Please note: Sharepoint does not meet the requirements for maintaining a digital TMF/ISF until a proper validation method is established (a pilot is currently underway at Amsterdam UMC). For more information, refer to the statement by the Health and Youth Care Inspectorate (IGJ)

If the TMF/ISF/IPSF contains both paper (i.e. hard copies with wet ink signatures) and digital records, clear cross-references must be indicated between their respective storage locations to show that both components constitute one comprehensive study file. This also applies to records completed and stored by (external) vendors and/or across different departments, such as the pharmacy file or calibration lists for specific medical equipment.   

Research Support:

The Clinical Monitoring Center (CMC) offers expert guidance on maintaining the study file. As part of their monitoring procedures, CMC also reviews proper use of the TMF/I(P)SF index and the filing of corresponding documentation. For any questions, please contact the CMC Helpdesk.