Filing Trial Master File

Verial eTMF: an electronic Trial Master File solution

Triall’s first software solution ‘Verial eTMF’ is a blockchain-integrated document management solution that supports clinical research professionals in building and managing their electronic Trial Master File (eTMF). Triall is co-developing this solution together with its main technology partner Sphereon. Uniquely, Verial eTMF enables users to generate verifiable proof of the integrity of their clinical trial data by utilizing the Factom Protocol’s blockchain infrastructure. In summer 2019, a beta version of Verial eTMF was given green light for use in a real-world clinical trial (credited as the world’s first clinical trial on the blockchain). The application is now being onboarded and used in multiple clinical trial consortia.

This post was updated on July 14 2020.

Document management is a common denominator throughout clinical research. All stakeholders involved in clinical trials are required to maintain and store trial-related ‘essential’ documents in compliance with Good Clinical Practice (GCP) and applicable regulations. These essential documents may be audited and inspected by monitors and authorities at any time to confirm the validity of the trial and the integrity of the collected clinical data. To support the correct and effective management of all of these filing responsibilities, GCP requires essential documents to be collected in a Trial Master File (TMF), today an electronic variant, the ‘eTMF’. The essential documents contained within the eTMF should enable regulatory authorities to reconstruct trial activities and key decisions made, providing conclusive evidence that a medicinal product candidate is safe and effective, and qualifies for market introduction. Depending on the phase and size of the clinical trial, the eTMF can comprise several thousand documents. The responsibilities related to the organization and management of the eTMF usually fall into the hands of Clinical Research Associates (CRAs) working at the sponsor organization (i.e. the biopharmaceutical firm that initiated the trial) or specialized service providers (‘CROs’) as well as research nurses working at the hospitals where the clinical trial is to be conducted.

Difficulties in managing the eTMF
The organization and management of the eTMF can be complicated, especially in multi-country trials that involve a large number of research sites. To illustrate, a recent industry-wide survey concluded that virtually all clinical researchers experience issues with keeping track of their documents and data in their clinical operations. Consequently, failure in adequate recordkeeping is a persisting industry pain point, leading to significant trial delays and, ultimately, putting patients at risk.

“A recent industry-wide survey concluded that virtually all clinical researchers experience issues with keeping track of their documents and data in their clinical operations”

Moreover, failure in recordkeeping also results in the costly reiterations of research activities. While academia and smaller industry typically perform the early stages of clinical development (phase I & II), Big Pharma’s involvement is essential for completing the later stages (phase III) and bringing a candidate product towards market authorization. Taking over projects from smaller stakeholders, Big Pharma are often seen to reiterate research activities because they cannot guarantee data quality and validity due to documentation inadequacies in upstream trial phases. This leads to an enormous amount of unnecessary costs and ultimately delays time to market as well as driving the commercial price of the product under investigation.

To make things worse, fabricated or concealed clinical research data continues to be an issue. Over past years, marketed drugs have been recalled for lacking safety or efficacy on several occasions, underlining that inadequate recordkeeping can put trial subjects and patients at risk. These cases come at high costs for already risk-averse biopharmaceutical companies and failure to prove adequate recordkeeping is thus a major obstacle for the progression of medical solutions initiated by academia and smaller industry across the pharmaceutical value chain.

Verial eTMF, a blockchain-integrated document management solution
Triall commits to addressing these issues and thereby enable a future of smarter, safer and more efficient clinical trials. Uniting a deep understanding of clinical operations with blockchain and document management capabilities, we have developed a blockchain-integrated document management solution that supports and streamlines the organization and management of the eTMF. Uniquely, it also enables the user to prove the existence and authenticity of their essential trial-related documents by establishing an immutable audit trail of their evolution over the course of a clinical trial. This utility promises a breakthrough in the way the industry conducts its day-to-day clinical operations by improving the reliability and auditability of clinical research throughout the drug development chain, and fully answers to increasing calls for meticulous documentation as decreed by the US Food & Drug Administration (FDA), European Medicines Agency (EMA) and other regulators. Moreover, it provides a competitive edge for those stakeholders in the early stages of clinical development since Big Pharma companies are more likely to invest in further development without the need for costly iterations of clinical trials and/or the risk of expensive recalls.

The future of Verial eTMF
At Triall, we are continuously looking to improve Verial eTMF with other features that support our clients in decreasing manual workload and streamlining their clinical trial operations. We’re currently working on additional features for document oversight, auditing and reporting. Moreover, Verial eTMF will soon be enhanced with a blockchain-registered digital signatures module (enabling the parallel signing of any file type) and an automatic document classification module that utilizes AI/Deep Learning to recognize and classify trial-related documents as soon as these are uploaded to Verial eTMF, enabling the automatic structuring, naming and storage of these documents in the right folder.