Assessing Investigator Site File Systems for Clinical Research

This article was compiled using information from the eCF eSRA and eISF Teams by: Pablo Perez, Lead Quality Assurance Data Integrity, Astellas

More and more, clinical research sites are implementing electronic systems for managing essential records generated from conducting a clinical trial. Sites are either internally developing a system or purchasing an off-the-self solution. In either case, the records that the system will manage must meet data integrity principles, global regulations and regulatory guidelines for Good Clinical Practice (GCP) from FDA, EMA, MHRA PMDA and ICH to be acceptable for use for the clinical trial. The recent EMA “Guideline on Computerized Systems and Electronic Data In Clinical Trials”[3] section 4.6 Criticality and Risks, states “For systems deployed by the investigator/institution, the sponsor should determine during site selection whether such systems (e.g. electronic medical records and other record keeping systems for source data collection and the investigator site file) are fit for purpose.”

The eClinical Forum[1], a transatlantic, not-for-profit and non-commercial, technology independent group representing members of the pharmaceutical, biotechnology, and allied industries have created an assessment tool that is available for free to both Sponsors and Sites. The assessment tool is to determine GCP compliance of a site’s Electronic Investigator Site File (eISF) System for managing essential records used in a regulated clinical trials. Completing the tool is not a regulatory requirement; however, it may be used to demonstrate that regulatory requirements have been satisfied. Sponsors and sites can use the assessment to discuss any potential risks and appropriate mitigations. NOTE: Sponsor-supplied systems do not need to be assessed by the clinical research site. This assessment is only intended for investigator site supplied systems.

The eClinical Forum ISF assessment tool contains a set of questions based on regulations and regulatory agency guidelines for electronic systems used in clinical research as identified in the eClinical Forum “Requirements for Electronic Data for Regulated Clinical Trials[2] ”.  

The ISF assessment tool is available for free download (no information is collected in return), along with its “sister” assessment tool for assessing clinical reasearch source systems (e.g. patient medical records systems) from their website at www.eclinicalforum.org/site-sys-assessments.

The eISF assessment tool is of great benefit to all players in the clinical research realm. In particular, the following should be noted:

Clinical Investigators

• Clinical Investigators are encouraged to use this tool to assess their systems, for which they are responsible, that manage essential records that will be used in a clinical trial.
• A site should be aware that a “No” answer to a question does NOT mean that the site will be rejected, but rather that the Sponsor will work with the site to ensure that any potential risk is mitigated.
• It is the site’s responsibility with respect to system installation, validation and maintenance. This may be handled by their organization’s IT department and/or a vendor. In these cases, the site is still responsible for ensuring that these other parties are fulfilling these responsibilities for any system providing data/documents in the clinical trial through a contract/agreement.
• Sites should retain a record of this assessment for use in improving their system and processes and to assist them with future system assessments.
• A site can avoid multiple requests from different Sponsors for information pertaining to regulatory appropriateness of their system, as the same completed eISF assessment can be given to each Sponsor they work with for review.

Sponsors / CROs

• Sponsors are encouraged to ask sites to use this assessment tool to determine if a site’s eISF is GCP compliant.
• Sponsors should obtain a completed assessment from their site and this assessment should be retained in their Trial Master File.
• Sponsors may have additional questions for determining if a site is suitable for their clinical trial; however, the questions in this assessment are the minimum requirements based on US, EU and Japan regulations, guidance documents, directives and reflection papers. A list of all regulatory documents used as a basis for the assessment can be found at www.eclinicalforum.org/esra.aspx. 
• The assessment tool does not “certify” or “qualify” the site’s system but merely provides information to the Sponsor for evaluation of the appropriateness of site’s eISF. 
• It is up to each individual Sponsor to review a completed a completed eISF assessment and does not provide certification or an “answer” as to whether the site as a whole is appropriate – it only indicates the site responses to each question. If a site is not compliant with all the questions, we recommend that the Sponsor work with the site to find suitable mitigations for the potential risks. 
• If after reviewing a completed eISF assessment from a site, the Sponsor believes there are too many risks to warrant using the system, then the system (and perhaps the site) should not be used for clinical research. However, the site may be given a period of time to make necessary adjustments to comply with questions in the assessment and may ultimately comply such that the system can be used for clinical research.

Regulators

• Regulators benefit by a common assessment that is mapped to US, EU and Japan regulations, guidance documents, directives and reflection papers. 

The eClinical Forum commits to updating the eISF assessment questions as needed when updates are made to the underlying regulatory documents and/or new pertinent documents are released from any of the regulatory authorities listed above. The eISF Handbook and Assessment template can be downloaded for free at  www.eclinicalforum.org/site-sys-assmts.

All are encouraged to provide feedback to the eClinical Forum regarding interpretations of regulations, eISF assessment questions, etc. via ISFA@eclinicalforum.org.

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[1] The eClinical Forum’s mission is to serve the clinical research industry by focusing on those systems, processes and roles relevant to electronic capture, handling, and submission of clinical data.  For further information on the eClinical Forum, visit the website at http://www.eclinicalforum.org.

[2] “eCF Requirements for Electronic Data for Regulated Clinical Trials” is available to the public at www.eclinicalforum.org/downloads.

[3] EMA Guideline on Computerized Systems and Electronic Data In Clinical Trials https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-computerised-systems-and-electronic-data-clinical-trials_en.pdf