Electronic systems for managing clinical study documentation emerged in the 1990s and have evolved through three generations. One of these applications is the electronic trial master file (eTMF). Who needs an eTMF and why use it? Read on to find out.
Defining the Trial Master File
Before dealing with the “e” in eTMF, let’s start with the Trial Master File (TMF) itself. According to Wikipedia:
“In order to comply with government regulatory requirements pertinent to clinical trials, every organization involved in clinical trials must maintain and store certain documents, images and content related to the clinical trial.”
This sentence establishes the need for a TMF with great clarity.
The definition does not claim you need a trial master file per se. It merely says the organizations involved with clinical trials must “maintain and store certain documents.” Those documents can be paper or electronic, located in one place or several places, and referred to as the TMF or as “Ken’s Folder.”
The idea of calling the central file for a clinical study the “TMF” is a convention, not a requirement. Having it centralized is not a requirement, just common sense. But one way or another, the sponsor of a clinical trial is responsible for ensuring that the documents that describe and govern the study are collected, maintained, and managed, and easily presented in the event of an inspection by the regulatory authorities.
The Regulatory Authorities are quite clear on this fact: you need a TMF.
The Regulatory Requirement for a TMF
In the EU, the regulatory requirement for a TMF is quite specific. The EU Commission’s Directive 2005/28/EC 63 Chapter 4 states ‘the trial master file shall consist of essential documents, which enable both the conduct of a clinical trial and the quality of the data produced to be evaluated.” And more recently, the European Medicines Agency provided guidelines that state that “The clinical trial master file shall at all times contain the essential documents relating to that clinical trial.”
In the US, the regulatory requirement for a TMF is less clearly stated but quite clear nonetheless. The FDA requires trials to be conducted in compliance with ICH Good Clinical Practice (GCP), and the ICH, in turn, dictates the need for a TMF and has published a minimum set of essential documents for the TMF.
“In the US, there is no specific requirement from FDA for companies to prepare a trial master file, but if the regulatory authority requires ICH GCP to be followed, then there is consequently a requirement to create and maintain a trial master file.” – Trial Master File (TMF): FDA Expectations From Sponsors And Sites
The Critical Role of an eTMF
As for an eTMF – electronic Trial Master File – you do not need one. But you most surely want one. Because just as it is true that you do not need a word processor to create documents, things are a lot easier if you have one.
The processes around creating, gathering, and managing the files and documents related to a clinical trial are complicated and daunting. There are hundreds of types of documents, some based on specific forms – thousands of documents all told.
These documents are authored by different people in different locations. Many have to go through specific review and approval processes, and many include signatures. They all need to be authentic versions of original documents and protected from unauthorized access.
Collecting the documents from clinical sites, investigators, and the rest of the study team manually and storing them in a central binder is possible. It’s just hard. An eTMF system automates many of the required processes.
Today, many documents are in electronic format. They are designated as electronic records and subject to specific regulatory rules governing electronic records. In the US, the FDA regulations on electronic records related to clinical studies are included in the set of rules referred to as 21 CFR Part 11. These rules provide explicit requirements for managing and processing electronic records, and eTMF systems include the functionality to address those requirements.
Who needs an eTMF? Any organization involved in clinical trials needs to manage the documents and files created during the trial, and everyone involved needs a place to store those documents – a TMF. If you prefer not to manage the process solely through fax machines and hole punches, you will benefit from an eTMF.