Beyond Old eTMF Technology

In a business niche as highly critical, closely scrutinised and heavily regulated as pharmacovigilance it remains a puzzle why clinical development organisations struggle so often with the “end of process task” of distributing Safety Reports*. These are commonly known as Suspected Unexpected Serious Adverse Reaction or SUSARs. Timely safety report distribution is important because of its part in improving patient safety but also due to the compelling regulatory obligation to distribute this material promptly.

A Pharmacovigilance Process Summary

  1. Site reports Serious Adverse Reaction (SAR) within 48 hours.
  2. Sponsor determines if SAR is unexpected or not.
  3. Sponsor reports SUSAR to relevant regulators within days (for EMA within 7 days and typically 15 days for the FDA).
  4. In parallel to step 3 the sponsor has a responsibility to promptly inform other sites once the matter is identified as a safety issue. While there is some scope for interpretation here, “promptly” is normally interpreted as meaning a number of days and not some longer period of time. Typically sponsors will aim to distribute safety reports within 15 days.

For reference here is how the FDA explain things – p16 of FDA Guidance Safety Reporting Requirements for INDs and BA/BE Studies.

The reality is that this end of process task sounds simple to define but it is in fact pretty complex and time critical. In addition – organisations are often so blindly addicted to using email that alternative, more dynamic and reliable means of information distribution are strangely alien and fantastical. But why not use distribution means that allow for active information distribution, with real-time dynamic readership information? In an age where audience behaviour is closely tracked, isn’t it time you knew who has read your latest Safety Report, and more crucially who has not?

The Hype Curve & legacy eTMF

Across the spectrum of eClinical, sponsors and CROs have deployed a myriad of emerging and established technology - from EDC to IxRS. The electronic Trial Master File is no exception.

A principal characteristic of technology is that by the time it is widely deployed it is by definition approaching obsolescence. This coincides with that generation of technology approaching the 'plateau of productivity' on the Gartner Hype Curve.

By Jeremykemp at English Wikipedia, CC BY-SA 3.0,

Systems [and processes] deployed at this stage meet widely accepted industry norms, enabling consultants and service companies to build great businesses repeating cookie cutter deployments. The ability to apply the learning curve effect of their experience lowers cost and risk for late adopter clients.

However, legacy challenges soon kick in and new approaches emerge earlier on the hype curve. The eTMF sector is very much in this state in 2021. There are a handful of well known solutions provided by strong, credible companies with a proven track record that are committed to the technology and deployment patterns they’ve invested in over many years. Simultaneously there are new entrants that emerge with offerings that benefit from smarter implementations and slicker user experiences compared to those of the segment leaders.


Some time ago, Paul Fenton, CEO of Montrium articulated his view of where TMF technology needs to move. A key concept is to include not just documents but 'events' in your TMF. Events are crucial to tell the story of your study after it has completed. However events are currently substantially missing, ignored or 'un-fileable' in many TMF deployments.

A central concept of myClin since its inception has been the study timeline. This most obviously manifests itself as a visual stream of consciousness for the study that users peruse and review. The study timeline view is easily filtered, e.g. for required actions (to dos), specific items (where’s that latest safety report?) and critically to document events such as monitoring visits.

With a group calendar built in, a substantial part of what Paul described as “TMF Events” are already included just by using myClin to schedule and document this trial activity. From experience in regulatory inspections and audits it’s clear that these events have helped our clients provide cogent and coherent accounts of their studies - allowing themselves and the Inspector quick, direct access to the material that matters most in the TMF.

Beyond the legacy eTMF

Ultimately, you build a TMF to demonstrate to future inspectors that you, your sites and your CRO(s) ran the study according to GCP and to underscore the integrity of your core clinical data findings. You must be able to walk an inspector through a reconstruction of your trial. You need to tell the story of your study which is why so many inspection readiness exercises start with a storyboard.

Current eTMF systems using mature technology, implemented with the narrow scope of simply archiving regulatory documentation miss out on a tremendous opportunity to improve study conduct. For example it is incredible that most TMF deployments exclude investigator site access to the TMF and often even the sponsor clinical team is unable to directly access the archive! They also exclude key parts of the study story such as the events noted above. Events happen constantly in every study and often define the framework to your study timeline or storyboard. Think First Patient In, Last Patient Out and all points in between. However it’s impossible to discern this story arc in most TMFs.

Too many eTMF deployments are little more than repositories for the final versions of your documents. Too often sites have no access at all. Frequently content is not organised and coded until late in the study or even after it closes where interventions are too little, too late.

It’s time to move on from these old approaches and old technologies. Emerging TMF solutions are moving into the mainstream and provide an opportunity leap forward for those companies facing the legacy TMF challenge. For example you can automatically capture the story of your study as it occurs by using myClin to track compliance, readership and controlled distribution of your critical information assets. Generate contemporaneous evidence of your Good Clinical Practice by letting myClin passively and patiently record your Oversight activity.

Isn’t it time you took a closer look?