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What is an Investigator Site File (ISF)?

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Location Settings

Asia-Pacific

AU -  Sydney
AU -  Melbourne
AU -  Brisbane
CN -  Hong Kong
CN -  Shanghai
IN -  Bangalore
MY -  Kuala Lumpur
PH -  Metro Manila
KR -  Seoul
CN -  Taipei City
TH -  Bangkok
NZ -  New Zealand

North America

US -  Boston

GLOBAL

English

An Investigator Site File (ISF) contains essential documents which shows that the clinical trial site and Investigator are following the regulatory requirements set out by the ICH GCP guidelines. According to the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, essential documents are defined as “documents which individually and collectively permit evaluation of the conduct of the trial and the quality of the data produced.” The ICH GCP 4.9.4 guideline states that “the Investigator and Institution should maintain the trial documents as specified in the ‘Essential Documents for the Conduct of a Clinical Trial’ guidelines.

An ISF plays a crucial role in the outcome of the clinical trial and should be established once a Clinical Trial site has been confirmed by the Sponsor. The Principal Investigator (PI) or an appointed delegate is responsible for setting up, maintaining and completing the ISF. It is the responsibility of the PI or the delegate to ensure that all the essential documents are collected before the trial begins and that the ISF is updated throughout the duration of the study and archived as part of the Clinical Trial Agreement with the Sponsor. 

Essential Documents 

All essential documents, including any correspondence should be placed in the ISF within 5 business days of the receipt. The essential documents are to be made readily available for monitoring, Sponsor audits and regulatory inspections.

The essential documents that should be included in the ISF include: 

  • Trial Protocol 
  • Participant Information Sheet and Consent Forms 
  • Investigator Brochure 
  • Regulatory documents, applications and approvals 
  • Delegation Logs 
  • Safety Reports 
  • Correspondence between delegated site staff and Sponsor

Pharmacy File 

A Pharmacy Folder is also included in the ISF (when applicable). It lists the recruited participants, Investigational Product shipping details, receipts and accountability documents. An up-to-date Trial Protocol and Investigator’s Brochure should also be included. The Pharmacy File is kept at the site pharmacy and is maintained by the delegated pharmacist. 

Paper and Electronic ISF (eISF)

Certain information should be included on the cover and spine of a paper ISF folder. This information includes: 

  • A Human Research Ethics Committee (HRECS) reference number and local project number 
  • Name of Principal Investigator
  • Study name 

If a document is removed from the ISF, there needs to be a note explaining why it was removed and where it was moved to. 

The same controls should be put in place for using an electronic ISF. When converting paper ISF's to electronic copies, they should be validated and used with quality control checks to ensure that no data was lost during the conversion.  

Investigator Site File Outline 

Section 1: Contact Details

  • Contact list of study personnel and site staff 
  • Contact details of external vendors 

Section 2: Investigator’s Brochure/Product Information

  • Current versions of the Investigator Brochure and Product Information Forms
  • Previous submitted versions 

Section 3: Protocol 

  • Current approved version
  • Previous approved versions and updates 
  • Signature pages 

Section 4: Participant Information and Consent Form

  • Current approved versions 
  • Previous approved versions 
  • Signed Informed Consent forms 
  • Signed Informed Consent Tracking Log 

Section 5: Participant Tools 

  • Patient Card, Diary or Questionnaire (if applicable) 
  • Current approved versions 
  • Previous approved copies 
  • Translation certificates (if available) 

Section 6: Advertisement for Trial Participant Recruitment 

  • Current approved version 
  • Previous approved versions 
  • Translation certificates (if available)

Section 7: Case Report Form (CRF) 

  • Current version (blank sample) 
  • Previous version (blank sample) 
  • Completion guidelines 
  • Signed, dated and completed CRFs 
  • Documentation of CRF edits made

Section 8: Source Documents 

Section 9: Ethics 

  • Initial submission 
  • Amendments 
  • Progress Reports 
  • Ethics Composition 
  • Notification of Safety Reports 
  • Notification of Non-compliance and Protocol Deviations 
  • Correspondence

Section 10: Governance 

  • Site Authorisation Letter 
  • Post Authorisation Submission and Authorisation Letters 

Section 10A: Regulatory Documents 

  • Clinical Trial Notification (CTN) or Clinical Trial Exemption (CTX) forms  
  • Therapeutic Goods Administration (TGA) acknowledgement letter 
  • Correspondence 

Section 11: Study Personnel 

  • Delegation Log/Signature sheet 
  • Curriculum Vitae (CV) (including GCP and Medical License, etc) 
  • Training log and documentation 

Section 12: Agreements 

  • Signed Confidentiality Agreement
  • Signed Clinical Trial Agreement 
  • Other relevant agreements/contracts 
  • Insurance Certificate 
  • Indemnity 

Section 13: Participant Logs 

  • Participant Screening Log 
  • Participant Enrolment Log 
  • Participant Identification Log 
  • Participant Visit Tracking Log 

Section 14: Investigational Product (IP) 

  • Instructions for handling the IP 
  • Shipping and receipt records 
  • Dispensing and Accountability logs 
  • IP Destruction Logs 
  • IP Storage and Temperature Logs 
  • Decoding and Un-blinding Procedure 
  • Sample of labels attached to IP containers 

Section 15: Randomisation 

  • Instructions 
  • Un-blinding process 

Section 16: Monitoring 

  • Site Visit Log 
  • Visit Correspondence (appointment confirmation and follow-up letters) 

Section 17: Laboratory 

  • Normal values and ranges for medical procedures and tests included in protocol
  • Certification/Accreditation/Established Quality Control/Validation for medical procedures and tests 

Section 18: Biological Samples 

  • Sample Log 
  • Sample Handling Manual 
  • Sample Shipping Record 
  • Laboratory Manual and Certification 
  • Shipping Materials 
  • Samples Destruction/Return Records 

Section 19: Safety Reports 

  • Serious Adverse Event (SAE) Tracking Log 
  • SAE Reports which have been submitted to the Sponsor 
  • Safety Reports 

Section 20: Study Reports/Publications 

  • Interim Report and Data Safety Monitoring Boards (DSMB) Reports 
  • Final Clinical Study Report 
  • Relevant Study Publications and References 

Section 21: Study Meetings 

  • Investigator Meeting (agenda and presentation) 
  • Site Initiation Visit (agenda and presentation) 
  • Other relevant meeting documentation 

Section 22: Correspondence

  • Correspondence with Trial Sponsor 
  • Correspondence with Site Staff 
  • Correspondence with Laboratory/Vendors 
  • Other relevant correspondence 

Section 23: Miscellaneous 

  • Newsletters 

All essential documents found in the ISF are required to be filed and stored in a secure location (a locked office or an electronic filing system with password protection). After the clinical trial has ended, all essential documents need to be archived in accordance with the Clinical Trial Agreement and the NSW Health Record Retention Policies. A Sponsor must give their written permission before any older ISFs are destroyed and one copy must always be kept for archiving purposes.

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