What is an eTMF - electronic Trial Master File?
Before diving into the world of digital it is perhaps useful to remind ourselves of the origins of the Trial Master File (TMF). The TMF is the collection of “essential documents” (also known as regulatory documents) that are required to demonstrate clinical trials are conducted in accordance to Good Clinical Practice (GCP) guidelines and comply with the appropriate requirements of the regulatory bodies (e.g. FDA, EMA) for each jurisdiction in which clinical trials are being run. The European Medicines Agency Guideline (EMA) defines “A TMF is the collection of essential documents that is used by sponsors, CROs and investigators/institutions for the management of the trial and by monitors, auditors and inspectors to review and verify whether the sponsor and the investigators/institutions have conducted the trial in line with the applicable regulatory requirements and the principles and standards of GCP”
As Wikipedia further points out “TMFs historically have been paper based and stored in filing cabinets”
Moving from Documents to a Structured Content Specification
A special interest group (TMF Reference Model) was established from the Drug Information Association (DIA) member community in 2009 to create a taxonomy/classification that would essentially define a structure for the Trial Master File. This structure would specify the areas of the clinical trial represented (e.g. Clinical, Data Management), the physical documents within each area and other data (called metadata) about these respective documents that need to be tracked. The first version of the Trial Master File Reference Model was released in 2010 and is now in its 3rd major release (tmrefmodel). Whilst the reference model is not endorsed by any standards body (such as ISO) it is widely supported by vendors and companies as a way to standardize the naming, collection and storage of Trial Master File documents for clinical trials.
Roll on forward then to the electronic Trial Master File (eTMF) which now provides the encompassing technology to manage both electronic and digital documents in a system.
What are the Key Requirements of an eTMF System?
Typically as a minimum these systems should provide:
- Support for the TMF reference model (structure and content naming)
- Ability to customise the reference model where additional document types are required
- Document upload to the electronic filing system
- Support for multiple document versions
- Indexing of documents so that you can search the document store
- Security to ensure controlled access is provided and the system can track actions being performed via an audit trail
- Document workflows to support quality processes
- Integration with other clinical systems and the ability to export the Trial Master File content between eTMF systems and companies
- Metrics and reporting
The TMF reference model team has also released a standard for exchanging eTMF documents which can be used to transfer content from one eTMF to another.
The Rise of the Machines
The eTMF systems market has evolved with different technologies being utilised to support the needs of an electronic trial master file:
- Electronic Document Management Systems (EDMS) that are used in multiple industries and then configured/customised to support the needs of clinical trials. Examples include OpenText, IBM, Oracle, Documentum and others.
- Modern cloud based electronic filing systems (Box, Dropbox, Google Drive, Microsoft OneDrive/Sharepoint)
- Special purpose eTMF vendors who have designed a system to primarily support the needs of the electronic Trial Master File.
Electronic document management practices have been commonplace in other industries. The clinical trials industry has been playing catch up but also improving document management practices by defining the structure of content more formally and gaining adoption for this structure as an industry wide guideline.
eTMF Vendors will differ in both their capabilities and pricing. Most companies should be able to identify eTMF systems that meets their requirements and budget.
The eTMF Benefits from Electronic Document Management
Automation delivers the first order benefits by the digitisation of paper documents and the efficiency gained by the implementation of electronic Trial Master File technology. These benefits include:
- Single source of truth - All users share the same current version of documents, eliminating paper copies and shared electronic copies
- Accessibility - The whole TMF can be viewed and searched across all clinical trials supporting distributed access for web based eTMF systems. Flexible security can further support different user roles and responsibilities across the organisation
- Responsiveness - Teams can react faster to notifications regarding the status of documents that include missing, incomplete or expired improving document management controls
- Compliance - A TMF that is well maintained and “inspection ready” reduces operational and enterprise risk for the organisation.
The Future of Clinical Operation Management
Whilst it is difficult to argue that the industry has made some real tangible gains in applying automation to document management workflows, our view is that the automation of business processes is only the first stage of the business benefits that can be realised. Some of the challenges that remain include:
- Fragmented clinical operations processes (clinical trial management, document management, study startup and others)
- Lack of integration between the separate systems being deployed for the aforementioned business processes resulting in duplication of information.
- Inability to provide an “integrated” view of clinical information management encompassing the operational processes and the associated document management workflows
- Additional technology costs of separate systems and the incremental costs of integrating them
An Integrated View of Clinical Operations
The Clinical IT applications that have emerged over the last 3 decades have predominantly mirrored individual functional needs (e.g. capturing clinical data, statistical analysis, managing a trial, managing essential documents, study startup, randomizing patients, managing safety and pharmacovigilance). Whilst this has provided the required automation needs of these functions, it might not address the enterprise information needs of organizations in a cohesive and elegant way and thereby inhibiting optimisation and business agility.
When applying principles for the design of an enterprise architecture that underpins and transforms a business, consideration for four different perspectives are necessary:
- Business processes
The PHARMASEAL Engility® Trial Management platform has been designed to address an enterprise view of clinical operations management where common processes are consolidated in the same platform as opposed to separate applications which:
- Allows common information to be defined once, reducing data duplication
- Promotes the integration of clinical operational processes around a common information and technology model supporting application consolidation
- Simplifying the technology and applications so that the number of systems can be reduced allowing multiple stakeholders to access different business processes based on their roles and responsibilities
- Provides an enterprise view of clinical operations satisfying both operational and strategic needs of the business
The Engility® platform, initially released in June 2019 provides an integrated management model encompassing clinical trial management with the associated trial master file document management. For many SME companies this provides a single solution to address two historic separate business functions and applications and begin the transformation of clinical trial management.