The 3 Essential Skills Your TMF Team Must Have

Skill #2: How to Perform Document Level QC

The life sciences industry faces a serious problem—a widespread trial master file (TMF) skills gap. There are simply not enough skilled TMF professionals to support the explosive growth and complexity of clinical research.

That’s where LMK Clinical Research Consulting’s TMF University comes in. LMK’s TMF University is the first and only internationally recognized and accredited certification program for working TMF professionals. TMF University allows TMF professionals of all backgrounds to access real-time and asynchronous remote TMF education courses tailored to meet learners at their level of expertise.

To celebrate the overwhelming success of TMF University and the hundreds of accomplished TMF University graduates, we’ve decided to publish this blog series sharing the three skills we feel your TMF team must have to achieve TMF health. In this second post of the series, we’ll cover one of the most basic, yet most essential, TMF skills: Document Level QC.

What Is Document Level QC?

For a TMF to be inspection ready, the TMF must be complete, correct, and contemporaneous (the Three ‘C’s of TMF health). Correctness, in the context of the TMF, means the TMF meets quality standards. Document Level QC, therefore, is the process of confirming that each individual document in the TMF meets all applicable quality standards. There are two main types of Document Level QC:

1. Non-Content: The purpose of non-content QC is to confirm a document meets all applicable quality standards. In general, this means a reviewer is evaluating a document to make sure it is final, legible, unique, and accurate, including meeting the standards of good documentation practice and ALCOA-plus principles (which means a document is attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available).

Although numerous aspects of a document are evaluated during non-content document QC, a TMF stakeholder performing this type of QC might ensure a document is legible in all fields. This reviewer would also ensure that all pages, signatures, and fields are present/complete and confirm that the document is not a duplicate. Non-content document QC also could cover many eTMF-specific document attributes, like verifying that a document has accurate metadata that reflects the content of the document.

2. Content: The purpose of content QC is to confirm that a document is both appropriate and relevant for inclusion in the TMF. ICH GCP guidelines, the TMF reference model, and your organization’s TMF index and SOPs all inform what documents are appropriate and relevant to the TMF. Content QC means ensuring that a document is both an essential part of, and accurate to, the narrative of the clinical trial contained within the TMF.

Evaluating document content as part of document QC requires using your critical thinking skills, drawing on past clinical experience, and possessing understanding of the individual narrative of your clinical trial. Content QC findings could include discrepancies between version numbers across a document category, incorrect site number assigned to an investigator, a document in the TMF belonging to a different protocol, or an interim monitoring visit date document as occurring before the site initiation visit.

Why Does Document Level QC Matter?

The fundamental regulatory purpose of the TMF is to contain the collection of documents, “which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. [1]” In other words, the function of your TMF is to create, store, and communicate the faithful story of a clinical trial, so that everyone, including regulators can have confidence that the data produced is reliable and that subjects were kept safe. Understanding—or even finding—your clinical trial’s story could be impossible if irrelevant documents are filed in the TMF or if the individual documents in your TMF are so low quality that they can’t be relied on or comprehended.

Sure, an illegible entry, a missing page number, or an unattributed strikethrough might not seem serious, but what if that entry is pivotal to establishing a patient is eligible for enrollment? What if there truly is a missing page and that page is related to a serious adverse event? What if that unattributed strikethrough is evidence of scientific fraud? Fortunately, the stakes are rarely this high, but that doesn’t mean they won’t be the next time you conduct document-level QC.

Even when individual document quality issues are relatively inconsequential, it’s hard to deny one simple fact: TMF inspection readiness begins with high quality essential documents. If the individual documents within a TMF are flawed, no TMF plan, TMF index, TMF QC cycle, or TMF reporting strategy can hope to help achieve TMF health. Each quality document filled is an individual brick forming the sturdy foundation of an inspection ready TMF.

You Can Close the TMF Skills Gap

Despite the critical importance of TMF health, TMF experts have suffered from the harmful notion that TMF management is clerical work and that all TMF professionals are simply document reviewers. But this couldn’t be further from the truth. All of today’s TMF professionals must have advanced skills in project management and clinical operations oversight to achieve the ever-increasing expectations of regulators. The only solution to close this TMF skills gap is to invest in the growth of TMF professionals through modern and dynamic TMF education.

If you are a TMF professional looking for more real-world knowledge on how to supercharge your team’s Document Level QC, check out our extensive library of blogs, case studies, articles, and webinars, many of which discuss the individual elements of document QC in greater detail. If you’d like to take your individual knowledge of the TMF to the next level, visit www.tmf-u.com to learn more about TMF University and enroll today!

[1] ICH GCP E6(R2) Section 8