How to Improve CRO Oversight by Bringing Your TMF In-House
To facilitate virtual TMF inspections and improve efficiency, the EMA encourages sponsors to provide inspectors direct system access to the eTMF on an ongoing basis. In response, sponsors have increased their willingness to bring the eTMF in-house and have CROs work directly within the sponsor eTMF.
Although sponsors agree that a sponsor-owned eTMF provides more control, they ask how to implement this strategy successfully.
I recently spoke with Pawel Rucki, senior manager of TMF operations at GW Pharmaceuticals, about GW Pharma’s transition to an in-house TMF model, benefits of sponsor TMF management, and best practices for making the switch.
Benét: As a sponsor, bringing your TMF in-house and having your CROs work directly in your eTMF has several advantages. The most common benefits we’ve heard from sponsors include more control over data, better oversight, reduced risk, and continued inspection-readiness. What are your thoughts?
Rucki: Yes. I agree with those. For us, the drivers were better oversight and collaboration.
Having an in-house eTMF application enabled GW Pharma to manage documents and TMF processes in realtime through automated workflows. By providing remote access to the system, CROs can review and approve documents directly, significantly reducing the number of emails exchanged, improving collaboration, and document management.
Additionally, by having one central eTMF, we can track KPIs per CRO or across all our CROs. Dashboards help us monitor TMF status and help ensure accountability. Another benefit is that we eliminated costly end-of-study migrations.
Benét: Managing an in-house eTMF with limited resources and convincing CROs to work within a sponsor’s eTMF are commonly cited challenges. How did GW Pharma address this?
Rucki: Our small team of three managed quite well, with IT support, so resources were not an issue. Once implemented, our focus was to ensure CROs were comfortable working with our system.
Your CROs likely have experience working in other sponsors’ eTMFs. However, it is still essential to build confidence and trust with your CROs. Address their concerns and make sure they are aware that you know what you’re doing.
Once we talked to our CROs about their concerns and showed them that we had the know-how, experience, and technology, they were on our side. One of our CROs confessed that 64% of their studies already used a sponsor eTMF, so they were familiar with making the transition.
Benét: How did you onboard your CROs to the new system?
Rucki: We used our eTMF for the first six months to learn the system before introducing it to them. Once we were confident with the system, we began inviting them to use it. The first CRO we worked with took a bit of time as the process was new. For the others, it was much easier because we already knew what it was going to look like and what elements we needed to discuss.
It was important that our CROs used the eTMF from the start of the trial in the study start-up phase. We stated our requirement upfront in the bid process.
Once they agreed, we set aside time to do the training, sign all the contractual agreements, and discuss the TMF plan. One of the CRO users said that, on the whole, they preferred our system to their own. It was very rewarding to hear that statement.
Benét: How should a sponsor ensure appropriate and secure CRO access?
Rucki: I recommend having your IT department assist with that. Most companies already have a process in place to manage external users, so you’ll need to comply with your IT team’s requirements. At GW, we use single sign-on for all end-users and couldn’t bypass that with external users. So we had to onboard them to our single sign-on and multi-factor authentication solutions.
Benét: How do you ensure accountability of CROs within your eTMF?
Rucki: The sponsor and CRO should discuss the KPIs for completion, quality, and timeliness. Accountability between sponsors and CROs should be documented in the contract based on the RACI and contained in the TMF plan. I mentioned earlier how our eTMF system allows us to share CRO-specific KPIs so that the CROs can make any corrections as necessary.
Benét: How do you manage the external users list given that the user list could change frequently?
Rucki: In our case, we manage user access in two steps. There’s access to the system (the CRO user accounts) and the study (permissions). IT manages the initial setup, and our internal team is responsible for adding users to the studies. Often a given CRO user may be part of several studies. They onboard once, but the study manager can add and remove them from different studies as necessary. If the user leaves the CRO, then we remove their account from the system.
Access control is set up as part of the TMF plan and filed in the eTMF. It is a living document where the CRO can request the addition or removal of users. It makes the process quite manageable.
Benét: Can you give us insight into how you train CRO team members on your sponsor eTMF?
Rucki: The more you invest in training, the better the use of the system is. In addition to our standard training, we developed customized training plans based on the various CRO roles and permission levels. There is no one-size-fits-all solution that would work for everyone. For example, contributors, managers, and viewers each had training tailored to their role. We also spent a day with a few “superusers,” training them on our processes and standards so they could be the first resource for other CRO users.
We also give superusers ongoing training and updates as the configuration changes or the system gets upgraded. We task the superusers to deploy that additional training to all the end-users at their CRO. We invest lots of time and effort in the training materials to ensure that they are of the best quality. This has eliminated just about all of the questions from our partner CRO end users.
Benét: You mentioned configuration changes. How do you determine if a change needs to be made?
Rucki: We meet with our CROs monthly to discuss configuration changes. We ask them if there’s anything we can do to make their lives easier. Are there any changes they would like us to make? We can turn around configuration changes within a month.
Remember your CROs will be the most important users of your eTMF, not you. They will put 99% of the documents there, so the system must work for them. CROs contribute 500 documents per week, while GW Pharma adds about 20 documents per month.
Benét: Many CROs have their own SOPs. How does this work?
Rucki: You can’t ask a CRO to use their SOP if they need to work on your system. That’s not going to work because your system is different, and they won’t be able to follow their SOP.
While you are writing your SOPs, you need to think about external user access and the process for managing. Our eTMF SOP includes process instructions and guidelines. That’s where we describe how the CROs should do the TMF reviews, the QCs, and the certification of the copy. However, we do look at the CRO’s processes and see how much of their SOP they can retain. For example, what do they check when they are doing the QC? If it’s complete, we let them keep it, and it’s better because they are used to it. If not, we provide instructions. If they can reuse part of their SOP, they should.
Benét: How do you ensure consistency across document QC resources?
Rucki: This is tricky because each CRO has a different approach to the QC of documents. We take it case by case. There are two ways to do it: 1) you can ask a CRO to provide a QC resource and agree on what standard of the QC you’re going to follow, or 2) you can outsource the QC completely.
We asked our CROs to do our QC. We didn’t want to have another vendor accessing our system on top of our CROs. Still, I have some colleagues at other companies who outsource their QC elements to a completely separate company. The benefit is that it gives them a consistent and objective approach between sponsor documents and CRO documents. But your company needs to assess what model would work best. Asking CROs to provide you their resources for QC is the more budget-friendly model.
Benét: The European Medicines Agency has stated they would like sponsors to have a single, live eTMF that enables direct access. This implies a desire to move to digital inspections. Do you feel comfortable with digital inspections?
Rucki: We have not yet had a remote inspection, but I have colleagues and peers at different companies who have. Once you implement a system, you always think about inspector access. Veeva provides inspector access out of the box. Inspectors know eTMF systems. They work on them every day for many different sponsors. You’re not going to be able to hide anything because they probably know that system better than you.
Ensure inspectors can get the information they need because it’s very frustrating for them if they can’t or too much hidden away from them. MHRA asked a colleague of mine (not at GW) to access their eTMF for a month after the inspection has finished. We need to be prepared for something like that.
Benét: Does having CROs working directly in your system add costs? What are the implications when it comes to the budget?
Rucki: This is a good question, and it was a reality check for us when we were onboarding the CROs. Yes, the CROs will charge you for using your system, but they would have charged you for using their system anyway. When you are onboarding CROs to your system, we find the numbers a little higher because they add time for training. You might need to add additional resources for superusers. The savings arise from the day-to-day management of the TMF, ensuring the TMF is appropriately overseen, and the inspection-readiness aspect.
Also, remember the cost of migration at the end of the study. When you get to the end of the study (without using an in-house eTMF), migrating thousands of records is very expensive. Whatever you would pay to have your eTMF from the start will be much less than the charge to migrate records at the end of the study if you didn’t. Migration can be a six-month project itself with such a high volume of records. You will claim massive savings [from using a sponsor eTMF], even if it looks like you will pay a little bit extra at the beginning.
Bringing an eTMF in-house is an important, strategic decision for a sponsor. The benefits can be numerous and even provide strong cost-advantages over not doing so, as Rucki discussed. Focusing on CROs’ needs and working as partners is the most important aspect; any sponsor considering doing so should be prepared to invest in that area. The results can lead to stronger collaboration, higher-quality documents, faster study results, and significant cost-savings by eliminating the need for end-of-study migrations.