The trial master file is a collection of all essential clinical documents that enable the conduct of the trial and quality of data produced which is to be stored, evaluated, and maintained.
An electronic TMF is the digital repository of all documents, agreements, contracts that are maintained and archived after every trial closeout. The major role of a trial master file is storing data in an organized way such that it is easy for audits.
All these documents are generated from the Sponsors, CRO’s, Laboratories, Regulatory agencies, Investigators and Ethics committees which are to be shared and updated timely. Below are a few challenges faced by paper TMF and eTMF.
- Being inspection ready
TMF – Organizations go through a struggle in maintaining paper documents to be ready for inspection. The data is inconsistent and cannot be shared with anyone. There is also a huge loss of time and expenses in managing compliance with the regulatory authorities.
eTMF – Documents are stored in multiple locations and during an inspection, the necessary documents are not located. All essential documents are prepared and updated at different times for weeks by different staff according to the regulatory requirements and are residing in the system but inaccessible during audits.
- Collaboration between Sponsor and CRO systems
TMF – Sponsor and CRO use variable filing systems and collaboration is a painstaking task. Oversight of the CRO is limited in the overall process of TMF and takes hours of reconciliation.
eTMF – Every document type that is generated in the Sponsor or CRO system must be tagged and filed in the eTMF. As there is a software conflict and no integration or visibility with the systems which will, in turn, hinder the effectiveness of eTMF.
- Metrics for monitoring
TMF – Some metrics have issues with paper TMF as they cannot be utilized with poor scanning quality. It is a highly time-consuming job of monitoring metrics for thousands of documents under different systems.
eTMF – Timeliness, Quality, and Completeness are the key parameters for metrics and are used constantly, but are not updated to keep the eTMF accurate.
- Implementation of eTMF
In order to speed up the clinical trials, electronic TMF is devised as an accurate method to access all clinical data in a timely manner. eTMF is centralized, easy to share, collaborate, even allows us to download and print when compared to paper TMF. But Industry is still accepting the change, according to the eTMF Survey 2015.
- Validation of the digitization process
TMF – Even in case of paper documents the sponsor needs to check for the validation process as there might be a loss or alteration of information. Logistics is a major concern as the documents go for approvals, then taken to the location for digitization. Hence there is no back up of data in case of missing documents.
eTMF – During the scanning of paper documents Sponsors keep a note on the validation process to confirm that the hard copies are legitimate. Auditors check the similarity between the scanned and original documents then they are archived and a backup is stored.
In this blog, we have dealt with a few challenges, there are other challenges such as archival & retention, destruction of paper documents, controlled access to health information and ownership transfers for retention. The one solution to these problems is the implementation of eTMF that is integrated with all other systems. All possible solutions to the above-mentioned challenges will be covered in our next blog.
References
https://tmfrefmodel.files.wordpress.com/2014/09/tmfrm_metrics-101_27aug141.pdf
https://www.swog.org/sites/default/files/docs/2017-10/Guidance%20on%20FDA%20Inspection.pdf
https://www.ema.europa.eu/documents/scientific-guideline/draft-guideline-good-clinical-practice-compliance-relation-trial-master-file-paper/electronic-content-management-archiving-audit-inspection-clinical-trials_en.pdf
By Mythri Raghunandan
