From The Editor | June 26, 2024

Insights Into TMF Challenges & Solutions — Part 1


By Dan Schell, Chief Editor, Clinical Leader

Nicole Palmer circle and apple headshot
Nicole Palmer

She’s been named one of the top 5 TMF experts to follow on LinkedIn. She’s got her own podcast. She offers an online eTMF specialist course. She worked at a CRO for nearly eight years, and … she regularly wears a bow tie (at least on LinkedIn). It’s Nicole Palmer, the CEO and president of consulting firm Granular Level, and my new favorite person when it comes to helping me understand all things TMF.

This is part one of a two-part Q&A I did with Nicole recently about a variety of issues surrounding the trial master file. In this part, she talks about the TMF Reference Model, moving to an eISF, and challenges with e-signatures.

If a new CRC or CTA is getting involved in updating the TMF, how much do they have to know about the TMF Reference Model, and where do they get that training?

NP: As a new clinical research coordinator (CRC) or clinical trial assistant (CTA) it’s important that you are onboarded properly. Training starts on day 1 and it should be ongoing training. Your initial training should include things like, your role, tasks, SOPs, protocol, Declaration of Helsinki, local and international regulatory requirements, and ICH-GCP. CRCs and CTAs will need thorough training on the CDISC Reference Model to ensure that their documents are organized and managed in a way where the documents tell the story of a clinical trial. Karen Roy, who is a leading TMF expert, and I had a great conversation where she shared her valuable insights on this topic. You can watch the full interview here to gain a deeper understanding of the importance of the CDISC TMF Reference Model and best practices. Also, I mentioned earlier that training is ongoing. It’s not, “I’m trained and then I’m done.” To keep up with the ever-changing regulatory requirements it’s imperative to have regular refreshers such as taking courses and attending webinars and industry conferences.

If a site is paper-based, and they want to move to an eISF (electronic investigator site file), aside from the standard opposition to doing something new, what challenges or new tasks should they expect during the transition?

NP: It’s really important to get everyone on board with this decision to go from paper to eISF, and it starts with a top-down approach. If leadership is excited and gets their team excited, the excitement will be contagious. I think it’s important to talk about the pros of the eISF and how it’s going to save you time and money, and how you will be able to work on more studies as a result. It’s also important to keep the excitement going and celebrate your migration milestones. You accomplish this by breaking down the goal into smaller goals. This way the goal is more digestible.

One of the new tasks that might be involved is starting with a migration plan. How are you going to do it, who is going to do it, and who is responsible for what tasks? For example, there will be a lot of scanning and uploading of documents. Who's going to be responsible for this? Who will be responsible for assigning metadata to those documents? Staff will need to be trained on this system. Who will be responsible for this? Do you need to integrate it with another system such as the CTMS? The key here is to be proactive and come up with a plan to stay organized and on track.

Are there any challenges a site should expect if they decide to start offering e-signatures? What are the 21 CFR Part 11 regulations regarding this?

NP: If you are thinking about implementing e-signatures within your organization, it’s important to understand 21 CFR Part 11- electronic records; electronic signatures. 11.3 (7) defines electronic signature as, “means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature.”

There are a few things you will have to think about when it comes to implementing e-signatures. It starts with careful planning. A few things to consider: Will it be compatible with the existing software that you are using? Will you be in compliance with 21 CFR Part 11? Who is going to implement the e-signatures feature? Who will validate it (this involves extensive testing and documentation)? How will you keep this sensitive information safe (data security)? What will the audit trail look like? Once you’ve implemented e-signatures and it’s been validated and you have the green light to use it, your staff will need to be trained on the new e-signature process. At first, this may sound overwhelming, but you have to look at the benefits and your return on investment. Implementing an e-signature is going to save you so much time. It’s going to streamline your processes and provide convenience to the signers with no more confusion regarding “is this a copy or a wet signature?” And, it provides real-time tracking. The best part is, it’s environmentally friendly.