Partnerships sometimes do not work out as intended. For medium size and smaller biotech companies…
The TMF is the official record of the clinical study for Regulatory Authorities, be it the FDA, Health Canada, or EMA. You must be able to present the TMF as a robust and complete package, that is clean! Quality data and audit inspection readiness are top-of-mind priorities for every CRO and their Sponsors. Which is why it’s so important to be certain your eTMF is inspection ready, and serves to expedite the process, eliminate redundancy, and enhance compliance with ICH-GCP requirements.
Quite simply, every best practice has been worked out through trial and error, and have evolved in the past decade through the development of new technology and platforms. With performant eTMF options now available, the important caveat to remember is that just because “Company A” has success with a certain initiative doesn’t mean that “Company B” can plug-and-play the same process and expect the same outcome. The technology is not everything, the team using it must be appropriately trained and coached to guarantee an optimal eTMF management.
Lean Team Effectiveness Requires an ‘All-Hands-On-Deck’ Approach
Prior to eTMF access your Lean Team members must be well trained on the eTMF system itself, the SOPs and Wis associated with the eTMF, as well as the study-specific plans that govern the timelines and content of your eTMF.
Cross-training in roles is also a requirement where CRAs are expected to maintain and upload site specific essential documents, CTLs (i.e. country-leads/project managers) to maintain country-specific documents, such as any Health Authority communications and approvals, or Canadian specific study plans that are filed in the eTMF.
In addition, due to a ‘2-pairs of eyes’ policy required to complete QC checks, there is no set expectation for the Lean Team that only CRAs will upload and only CTLs will perform QC checks prior to publishing. Often CRAs verify documents that CTLs upload and vice versa. For the Lean Team to work well cross-functionality capability is absolutely required.
To ensure success, your company culture, HR and training/coaching programs must also be aligned to support a Lean Team ‘all-hands-on-deck’ approach. Lean Teams function best when staff turn-over is very low as team cohesion and stability are critical to success.
If your team architecture constantly experiences CRA and/or project manager turnover, application of the ensuing eTMF Lean Team best practices and lessons learned are likely to fail.
Scimega’s typical eTMF Lean Team composition: is led by a Clinical Trial Leader/PM; with sufficient CRAs to manage participating sites; with no CTAs or archival document department. The eTMF Program Specialist oversees eTMF set-up and administration, including training.
Efficient eTMF Lean Team Start-Up Requires the Correct Tools
- Pre-production of easy to use and complete tools is a key component of quick eTMF deployment; eTMF management templates, Structure and Content listings, and a company-wide standardized document naming system.
- Engaging with all Stakeholders at the earliest possible stage, brings clarity to the system requirements and produces shortened timelines for Sponsor review of draft documents.
- Study Lead works in conjunction with the eTMF Czar, who can aid the study Lead and ensure that consistency is maintained across studies/programs.
APPROPRIATE Document QC Set-Up is Key
Determination of the document quality control process differs considerably depending on organization size.
- Large CROs = entire departments dedicated to document review pre-publishing to Records Center; and multiple pathways to reviews by different functional groups (Regulatory, Clin Ops, finally Publishing dept)
- Lean Teams = 1 Uploader and 1 Reviewer
Important Lesson that Led to Better Understanding eTMF Best Practice for a Lean Team
At the outset, Scimega predicted that in order to maintain an eTMF that was ultra-clean and audit ready, a series of QC steps were necessary to ensure each document was thoroughly reviewed and that only clean data would be present in the final published Records Center.
This was initially based on prior experience working with larger CRO teams/departments. In reality, Lean Teams can be very small, to the point that after processes were revised through trial and error, it was found that an alternative to an extensive multi-step QC process was the most sensible way to proceed, requiring only 1 CTL and 1 CRA.
If a multi-step QC process isn’t effective for your smaller Lean Team you must define the steps that are absolutely required in order to produce a clean eTMF.
- Reviewer must view each document in entirety;
- Reviewer must be able to confirm correct indexing/metadata.
These are the only verifications that actually need to be completed.
Performance is Proof
At Scimega current deletion ratios are tracked through defined processes under the oversight of the Program Specialist. The following outlines QC performance of 3 selected eTMF Lean Teams.
For nearly 6,500 documents, only 36 in total required deletion due to errors not caught during publishing. In the table we see one comparative outlier in regard to the rate of deletions in Study #3. Maintenance of KPIs, including deletion requests, and the review process, allow teams to upgrade their training to minimize introduced errors into the eTMF.
Drilling down further into the metrics for Study #3, batches of documents (14 and 11 respectively) were identified as erroneously published into the eTMF. Removing these outliers, the overall rate drops to 0.17%.
This level of performance demonstrates that a properly trained, Lean Team, using a single point of review during QC, is able to produce an exceptionally clean eTMF. Keeping in mind all foregoing points outlined above, with fewer review steps in usage, maintenance of checks and balances including proper oversight are key.
eTMFs must be maintained at audit ready status throughout the life of the study with scheduled reconciliations performed, so there are never any surprises in routine audits. To achieve this, proactive risk management and constant preparedness for inspection is undertaken as a matter of course.
At Scimega risk management is baked into our DNA, from upper management Governance committees to ongoing risk management tracking to regular and ongoing training at the CRA level. The eTMFs are no exception, maintained at audit ready status throughout the life of the study with scheduled reconciliations per the eTMF management plan.
Scimega Consistently Goes Above-and-Beyond
Scimega is a niche Canadian oncology CRO acting in Canada within the context of global cutting-edge oncology trials sponsored by small to mid-size biotechs. Skilled in collaborative vendor teaming, our oncology experts work with your team to devise innovative solutions specific to the unique challenges of your oncology clinical trial.
24 years of unparalleled Canadian oncology experience means in the face of an ever-changing clinical trial landscape our robust operations design, and KPIs that consistently surpass global industry norms allow us to go above-and-beyond for every one of your studies.
Contributed by: Julie Martin, CEO & co-Owner