In Europe today, each study's Trial Master File (TMF) is commonly still paper and is often scattered across many locations
in many countries. With this disparate model comes many disadvantages and risks. An Electronic TMF (eTMF), where documents
are brought together in one place, backed up electronically, and visible over the Internet from anywhere any time of day,
provides a solution.
In the world of a project team, the TMF does not get the attention it deserves. Document managers may use all their efforts
to create a perfect and up-to-date TMF, but the project team is always more focused on the key project milestones, such as
first patient first visit, end of recruitment, database lock, and final report production.
PHOTOGRAPHY: GETTY IMAGES ILLUSTRATION: PAUL A. BELCI
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The TMF, however, relates the story of the trial. According to ICH Section 8, it "individually and collectively permits the
evaluation of the conduct of the trial and the quality of the data produced" and it serves to "demonstrate the compliance
of the investigator, sponsor, and monitor with the standards of GCP and the regulatory requirements."
By law, we have to have TMFs—The European Directives of 2001 and 2005 and National Laws demand it, but also ICH GCP, the Declaration
of Helsinki, and Company SOPs require a TMF to be maintained. ICH GCP 8.3.11 requires the retention of "relevant communications
that document any agreement or significant discussions regarding trial administration, protocol violations, trial conduct,
or adverse event reporting." The TMF world as we know it
What is the reality of the TMF today? The majority of European companies still operate on paper TMFs, especially when studies
are contracted out to CROs. While some pharmaceutical companies do have active eTMFs in place, other companies have eTMF initiatives,
but often these do not capture the entire TMF, rather just the more essential documents.
The power of being able to review, audit, and inspect TMFs electronically is then lost, along with the business continuity
advantages of having the entire TMF electronic. Interestingly, a couple of the larger, more electronically oriented CROs are
initiating eTMFs, reinforcing the significant business advantages they bring to the table. Nevertheless, paper is still king
in Europe.
In the paper world, TMF documentation is spread across numerous countries, and even more locations. Storage facilities vary,
from environmentally protected rooms to the home offices of clinical research associates (CRAs). Inevitably, this multiple
location TMF ends up containing a huge amount of duplication (everyone wants a copy of all important documents) and consists
of multiple and variable filing systems that are isolated.
What is potentially more worrying is whether everyone is working from the same documents. There is nothing worse than reaching
an investigator site and realizing that they haven't received the most recent protocol amendment. Or doing some last minute
audit preparation and finding a key document is missing.
