There is a lot of discussion about taking ownership of the trial master file (TMF). We wanted to understand what was behind this thinking of sponsors bringing the TMF in-house, so we reached out to an industry maven, Janine Penman of JPScientific, to fill us in.
Who Typically Owns the TMF?
This question is a big one because there are a few players in the clinical trials ecosystem. For example, there are the sponsors of clinical trials, the contract research organizations (CROs) who help sponsors manage clinical trials, and the sites that run the clinical trials.
Penman said that there is no one answer to this question. However, if you look at this question from the perspective of who “officially” owns the TMF, then it’s the sponsor from a legal and regulator’s perspective.
But if you are asking who “manages” the TMF or takes care of it (what she called “the TMF Nanny”), then today, that responsibility lies primarily with the CRO. Many sponsors outsource their operations which means the CRO is setting up and utilizing the eTMF for the sponsor.
But there’s also a hybrid model, she said. In this model, the sponsor has the eTMF system that manages the TMF, but the CRO maintains it.
The question becomes how do we get to a norm where the sponsor takes control and brings the TMF in-house, and why is it important for them to do so.
How Different Sponsors Manage the TMF
There’s an inverted bell curve that Penman uses to describe the management of the TMF.
If you are a very small company, like a startup, and you are just getting into clinical trials (Phase 1 or Phase 2), the tendency is to own and hold the TMF in-house. Penman said it’s the path of least resistance. The sponsor needs to get the TMF up and running quickly, and because they are small and agile, it’s easier to take care of it themselves. Managing the TMF internally also mitigates much of the cost of that management.
The challenge is that sponsors use systems that are not validated or could be appropriate, but they are not validated for use. For example, SharePoint is not built for purpose or a validated system, but sponsors use it to manage the TMF (Dropbox is another example).
Next, you have larger sponsors who leverage full-service CROs and, as a result, outsource the TMF.
Then you have the very large vendors who often have multiple CRO relationships and see the benefit of having a single TMF in-house that all CROs use. In these instances, the sponsor isn’t typically only buying an eTMF but has bought into an enterprise solution that includes other systems like CTMS, eReg, and QMS.
Why The Sponsor Should Bring the TMF In House – It’s a Quality Question
One of the challenges for sponsors is the belief that electronic solutions are too expensive and cumbersome to use. But the reality is, Penman said, that there are eTMF solutions that are low-cost and can meet the sponsor’s needs.
But imagine a sponsor who has a lot of venture capital behind it. This sponsor outsources the TMF and deals with multiple CROs. So why would they want to bring their TMF in-house?
Penman said there is this sweet spot – the moment of questioning – “Is outsourcing the TMF the best thing for sponsors or vendors?” It’s important to point out here that CROs are vital stakeholders in the clinical trial, and they have an essential role to play in the upkeep and maintenance of the TMF. The question is about who maintains the eTMF system that houses the TMF – and who is responsible for the quality control of the TMF.
“When a clinical trial is started, there is transparency about how to share the TMF. Everyone knows what is in it and where there are stored. This transparency helps keep the system clean. But that transparency turns to opacity as you move through the conduct of a trial. And it’s no one’s fault. It happens through a shifting of focus and worrying about other things like enrollment, getting patients in and out, getting sites closed.
No one has the time to think about a TMF quality check. It simply falls by the wayside and is pushed to a ‘just in time type of cleaning.'”
When the sponsor allows the CRO to hold the TMF, they assume the CRO’s processes and eTMF are good, and the CRO uses them. However, Penman said they often don’t know if the CRO supports that process or how quality checks are done (and they are often insufficient).
“So we have we have maintained the culture of ‘inspection on demand’ as opposed to ‘inspection readiness,’ and I can promise you when ICH E6 (R3) comes out, inspection on demand is no longer an option. Inspection readiness – perpetual inspection readiness is what’s going to be required of you.”
Regulators are looking at ways to utilize remote monitoring to set up this norm where they can check your TMF anytime they want. The sponsor needs to prepare for this to happen.
Bringing the TMF In-House Does Not Have to Be Painful
Taking back the TMF doesn’t have to be painful for the sponsor, Penman said. They can set it up at the beginning of a study with the right processes in place and put it on auto-pilot. Then, when the study is over, the TMF is ready. She said there’s no need to staff or CRO staff to work overtime.
Penman talked about the power dynamics when deciding who gets the TMF. She said when CROs bid, they often put a line item in for the TMF, even when a TMF is not explicitly asked for. Doing so enables them to use their own processes. It’s plug-and-play for them.
“But when the sponsor holds the TMF and the eTMF application, that mini-ecosystem the CRO uses goes away, and they have to learn to work differently, which isn’t difficult; it’s just a change.”
The process of transitioning to managing the TMF in-house is not difficult. Penman said she has seen clients succeed with well-priced systems. All you need is a basic set of TMF processes, and it doesn’t require a special expert or an army of resources.
Penman joined us for a 7-episode podcast to discuss the process required for sponsors to bring the TMF in-house. You can listen to this first episode and then check out the rest to get her expert insights.
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