This guidance provides information and top tips on how to use and manage your Investigator Site File (ISF).
The Investigator Site File (ISF) supports the validity of the research, as well as the conduct and integrity of the data collected. It is important to keep all trial related essential documents to demonstrate compliance with ICH-Good Clinical Practice (GCP) guidelines and regulatory requirements.
ICH GCP E6 R2 Sections 8.2 – 8.4 lists the documents to be generated before, during, and after a clinical trial, describing the purpose of each document. Documents that reconstruct the conduct of the clinical trial must be filed in the ISF.
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The Principal Investigator (PI) is responsible for the maintenance of the ISF. The PI can delegate the maintenance to others, however the individual assigned the responsibility for maintaining the ISF must be identified on the delegation log and the duty signed by the PI.
It is imperative that timely and correct filing is achieved routinely after quality checking the documents. Site staff should keep the ISF complete and up to date. ISF storage conditions should ensure no risk of accidental destruction of study documentation. The site should be mindful and communicate with the Sponsor/CRO in advance of an Investigator leaving the site and/or any change in archival location of the study documentation.
Virtual ISF (eISF) : For electronic storage/archival, the Investigator is responsible to check the data at regular intervals during the retention cycle to demonstrate that it has not suffered any degradation.
A contents Index should be present in every folder - usually provided by the sponsor.
Follow the contents list to ensure that all essential documents are present.
Only file documents once and in the sections specified in the contents list.
When a document is not filed according to the contents list because it is filed elsewhere then this must be documented in the contents list or by means of a file note within the designated section.
Use file notes to indicate when documents are filed elsewhere or to perhaps indicate the reason for a missing document i.e. stored electronically.
Review the ISF in detail with the monitor at the site initiation visit (SIV) to understand how documents need to be filed. An ISF contents list is usually provided by the Sponsor/CRO to use as a reference.
Be clear with instructions to investigator and site staff as how to properly pseudonymise (redact/obscure all directly identifiable subject information) included in study-specific logs/forms and other study documents prior to sending to Sponsor.
Do the filing regularly (e.g., weekly) and in reverse chronological order (i.e., the most recent document of a type filed at the front).
Documents should be legible, dated and signed where appropriate. Essential documents should follow the same good documentation principles (ALCOA-C) as source documentation.
When multiple versions of a document are generated throughout the study, those documents must be version controlled (e.g. by version number and date) and all versions must be filed in the ISF.
Superseded documents should be marked by version, initialed, and dated.
An eISF has an electronic folder structure following the project-specific ISF contents list that includes project- specific core documents, forms, and logs.
When filing for an eISF, use a consistent dating format to ensure that all documents are chronologically sorted and use a naming convention that clearly identifies the document type and version.
For electronic storage/archival, the Investigator is responsible to check the data at regular intervals during the retention cycle to demonstrate that it has not suffered any degradation.
The eISF must be archived together with the audit trail.