Investigator Site File

What Is an Investigator Site File?

An investigator site file serves as a comprehensive record that details how the clinical trial was conducted and managed in accordance with regulatory standards and the study protocol. This collection of documents is used to verify that a clinical trial investigator and the clinical trial site have followed the regulatory requirements set forth by regulatory requirements outlined by the ICH (International Council for Harmonisation) and GCP (Good Clinical Practice) guidelines. Auditors and regulatory authorities also use an investigator site file to confirm that the rights and well-being of study participants are protected and that the data generated from the study is credible and accurate.

Key elements of an investigator site file are as follows:

Audit and inspection reports
If the trial has been audited or inspected, related reports and responses to findings are included in the investigator site file.

Data collection and handling procedures
Documentation of how data is collected, processed, and stored is captured in the investigator site file to show adherence to data quality and integrity standards.

End of study information
Once a study is completed, the final report, closure notification to the institutional review board (IRB) in the United States or independent ethics committee (IEC) in the European Union, and other relevant documents signifying the end of the trial should be added to the investigator site file.

Ethical approval documentation
Final approval documents and correspondence with the IRB or IEC should be included in the investigator site file to show that the study adhered to ethical standards.

Informed consent forms
Copies of the informed consent forms (ICFs) and any other participant information sheets are included in the investigator site file, because documents are critical in proving that participants were properly informed about the study’s nature, benefits, risks, and their rights.

Investigator and staff qualifications
The investigator site file should include resumes, training records, and other relevant documents that demonstrate that the investigator and staff are qualified and trained to conduct the study.

Protocol and amendments
The study protocol, which outlines the objectives, design, methodology, statistical considerations, and organization of a trial, should be included in the investigator site file. Any amendments to the protocol should also be included.

Safety reporting documents
Any reports related to the safety of trial participants, including adverse events and serious adverse event reports should be included in the investigator site file.

Study reference materials
The investigator site file should include any investigator brochures, study product information, and lab reference ranges, as these documents provide essential background information for conducting the study.

Trial management files
Any correspondence with the sponsor, trial monitoring logs, and other documents that help in the administration and management of the trial should be included in the investigator site file.

What Is the Difference Between an Investigator Site File and a Trial Master File?

There are many groups of clinical research documentation that must be created and maintained to ensure that a clinical trial is successfully executed and meets stringent compliance standards set forth by the ICH and GCP guidelines. Two of the important types of clinical research documentation are the investigator site file and the trial master file.

While both play important parts in the capture and preservation of data and documentation related to a clinical trial, they serve different purposes and contain different types of information. At the highest level, the investigator site file focuses on documenting the conduct of the trial at an individual sit.

Investigator site file

Digging into the details, the investigator site file is maintained at each site where the clinical trial is conducted and contains documentation that is specific to the site where the clinical trial is being conducted. The trial site’s principal investigator, who is responsible for ensuring that all necessary documents are included, updated, and preserved in an orderly manner, typically oversees the investigator site file for the clinical trial site.

Key documents included in the investigator site file are the protocol and its amendments, informed consent forms, correspondence with the ethics committee, documentation of investigator and staff qualifications and training, participant screening and enrollment logs, and records of study drug dispensation and administration. The ultimate purpose of investigator site files is to provide irrefutable documentation that the clinical trial conducted at a particular site meets the compliance requirements set out by GCP and ICH guidelines and to provide a record of actions taken and decisions made during the trial.

Trial master file

On the other hand, the trial master file is a collection of documents that detail the conduct of a clinical trial so that it can be reconstructed and evaluated as needed. The lead sponsor or contract research organization (CRO) overseeing the trial is typically responsible for overseeing the trial master file.

Unlike the investigator site file, the trial master file includes not only site-specific documents from each trial location, but also documents from across the trial, such as the trial protocol, trial design documents, the trial’s statistical analysis plan, the final report, and correspondence with regulatory authorities. Similar to the investigator site file, the trial master file also serves as an official record of the clinical trial and demonstrates that the trial was managed according to GCP and ICH requirements. The clinical master file is used for audits, inspections, and reviews to validate the integrity of clinical trials and the quality of results and data produced.

Investigator Site File vs. Trial Master File at a Glance

When Should the Investigator Site File for Essential Documents Be Set Up?

An investigator site file should be set up at specific stages throughout the lifecycle of a clinical trial to facilitate smooth conduct and management of the study as well as maintain compliance with regulations.

Investigator site file setup before a clinical trial commences

According to best practices and regulatory guidelines, the investigator site file should be set up at the very beginning of the clinical research process after the trial site has been confirmed. Setting up the investigator site file at the outset is important for three primary reasons:

1. It ensures that all necessary documents are in place before the trial begins, which provides a solid foundation for the study’s conduct and reporting. The initial documents should include essential documents, such as the final version of the study protocol, the investigator’s brochure, trial-specific training materials, informed consent forms, correspondence with the ethics committee, IRB/EC approvals, and documentation of investigator and staff qualifications and training.
2. Enables ongoing documentation of trial-related activities to be collected and organized in a centralized location with additional documents being added to the investigator site file as the file progresses, including participant screening and enrollment logs, records of study drug dispensation and administration, and other documents pertaining to the conduct of the trial at the designated site.
3. Helps to ensure and provide supporting documentation of the trial’s compliance with GCP and ICH guidelines as well as other regulatory requirements.

Investigator site file setup continues through the lifecycle of a clinical trial

In addition to being set up at the beginning of the trial, the investigator site file must have new sections set up as the trial progresses. This involves regularly updating the file with new documents and information as they become available. This includes setting up sections for records related to participants’ visits and other activities, amendments to the study protocol or other study-related documents, and copies of ongoing communication with the sponsor and regulatory authorities.

At the end of the trial, a wrap-up report will need to be created and set up in the investigator site file. This final documentation, created and assembled upon the conclusion of the trial, includes the final report, close-out visit documentation, and correspondence with the IRB/EC regarding the study’s completion. Once completed, the investigator site file should be archived in long-term storage.

Is the Investigator Site File Part of the TMF?

While closely related, the investigator site file is not technically a part of the trial master file (TMF), but rather complements it. An investigator site file can be seen as a subset of the TMF, focusing on the specifics of the trial at an individual site, while the TMF provides a holistic overview of the trial’s conduct across all trial sites. And, although the investigator site file and TMF have distinct roles and content, they are interconnected, with the investigator site file forming an integral part of the TMF.

In a clinical trial with multiple sites, a TMF will contain multiple investigator site files. During inspections or audits, regulatory authorities may review both the TMF and investigate individual investigator site files to ensure that the trial is conducted in compliance with GCP and ICH guidelines and other applicable regulations. The completeness and accuracy of investigator site files and TMF are vital for demonstrating the validity and integrity of a clinical trial.

Ensure Compliance and Gain Operational Benefits with an Investigator Site File

An investigator site file plays a crucial role before, during, and after a clinical research trial. In addition to supporting compliance requirements, creating and maintaining investigator site files provides a number of benefits for clinical trials around the world, including the following.

• Enhances communication

  An investigator site file promotes clear and efficient communication between the investigator site, sponsors, monitors, and regulatory authorities by ensuring that all stakeholders have access to the same documentation.

• Ensures Inspection Readiness

  An investigator site file helps trial sites comply with regulatory requirements and guidelines by serving as a central repository for all essential documents needed for regulatory inspections and audits.

• Facilitates oversight:

  Sponsors and monitors can use investigator site files to oversee and manage the conduct of the trial at multiple trial sites in a consistent manner. It helps them verify that the study is being conducted in accordance with the protocol and applicable regulations.

• Helps identify risks:

  An investigator site file helps identify and manage potential risks associated with the conduct of a clinical trial, including risks related to data integrity, participant safety, and protocol deviations.

• Streamlines inspections 
  A well-maintained investigator site file can significantly streamline regulatory inspections and audits. When all required documents are organized and readily accessible, it facilitates a more efficient review process. 
• Optimizes resources 
  Having a well-organized investigator site file can save time and resources by minimizing the risk of missing documents and reducing the likelihood of delays and errors. 
• Supports training 
  An investigator site file can be used as a resource for training new trial site staff, ensuring that they are familiar with the trial protocol, procedures, and documentation requirements. 

While sometimes tedious, an investigator site file is helpful as it ensures the overall success and reliability of clinical research studies while improving operations.

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Last Updated: 18th April, 2024

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