For clinical researchers, the note to file, or NTF, is the mosquito that you can hear under the covers or the flat tire on the way to the interview. When left unchecked, the NTFs multiply to fill the trial master file, or TMF. When used to reduce confusion, NTFs reliably perpetuate it. When used to prevent inspection findings, NTFs often provoke them. So why do NTFs persist in clinical research when they consistently cause us so much pain?
The reason for our shared dependence on the note to file lies far below the surface and in the most fundamental emotions, beliefs, goals, and values that motivate our work in clinical research. There is a path forward to a healthier, less NTF-reliant future, but it means dispensing with the NTF as a short-sighted remedy and rediscovering the true purpose of TMF health.
In this article, we’ll define the note to file in clinical research, consider the elements of the NTF, establish the importance of the NTF mission statement, and give you the tools to put your team’s NTF mission statement into action.
What is the note to file in clinical research?
Let's take a look at some of the key functions of a note to file:
- A note to file in clinical research is a memo filed in the TMF that provides additional information or detail to study conduct then would otherwise be captured in expected TMF documents.
- NTFs are most commonly used to clarify discrepancies, errors, and omissions. Blank document signature lines, incorrect signature dates, and missing form fields are common triggers for NTF creation.
- NTFs also regularly act as a placeholder for a missing study document or to clarify one of many types of non-standard events, like an out-of-window monitoring visit, contradictory log entry, or complex enrollment decision.
Elements of the note to file in clinical research
At minimum, a note to file should embody the basic elements of clinical research good documentation practices, which are often abbreviated as ALCOA (Attributable, Legible, Contemporaneous, Original, and Accurate). In addition to following good documentation practices, an NTF should provide a clear record of the author, the date on which it was created, the protocol to which it applies, and a complete narrative about the issue (and resolution) to which it pertains.
Although policies may vary depending on the standard operating procedure (SOP) or filing structure of an institution, the NTF may or may not be signed and should then be filed in the TMF with, in the place of, or otherwise linked to the regulatory documents that most directly relate to the subject of the NTF.
What is a note to file mission statement, and why you need one
Many organizations have an SOP that governs the use of the NTF. Implementing a note to file SOP is a great practice that (hopefully) improves standardization of NTF structure and content. It also sets clear standards for when writing an NTF is appropriate, and more importantly, inappropriate. The SOP might also specify the due diligence requirements as part of addressing a problem with an NTF.
Even with a well written NTF SOP, however, many organizations struggle with poor-quality NTFs, too many NTFs, or both. For this reason, I propose that every organization develop their own customized note to file mission statement.
Now, let's create your note to file mission statement!
A mission statement fills in the gaps that training, work instructions, and SOPs cannot. Your mission statement gives your team well-defined expectations—both for when an NTF is needed, and more often, for when action should be taken to avoid the creation of an NTF.
Your NTF mission statement should contain a formal declaration of how NTFs fit within the purpose, values, and goals of your team. It should make it clear that if the creation of an NTF does not align with these goals, then an NTF should not be written. While I leave the exact content and structure of your NTF mission statement up to you and your team, I’ll share mine as an example:
“The purpose of the TMF is to tell the most accurate story of a clinical trial to protect the welfare of subjects and the integrity of the trial’s data. Because we value the narrative within the TMF, we pledge to support our team’s positive risk-taking, flexible thinking, and courageous decision-making to proactively and fearlessly improve TMF quality, rather than retroactively reach for the NTF. We believe that minimizing reliance on the NTF is a major component of achieving TMF health.”
3 steps to put your note to file mission statement into action
Putting your mission statement into action consists of three distinct phases:
1. Collaborative Development
Putting a note to file mission statement into action begins with the authoring process. All stakeholders who will be asked to adopt the NTF mission statement should be part of the workshopping process of developing a first draft. Developing the first draft should be an iterative process. In the workshop, the elements of a mission statement (purpose, values, goals) should be discussed in the context of the day-to-day TMF activities of your team. Although assembling your whole team for a workshop is a large investment of resources, offering your team the opportunity to tailor the mission statement to your team’s unique needs encourages buy-in. No one will adopt a mission statement they feel is imposed upon them.
2. Metrics-Driven Implementation
In the implementation phase, management must provide clear instruction of how TMF processes will incrementally change to reduce reliance on the NTF. The implementation of these changes should be monitored with clear quantitative metrics, such as the number of NTFs written in a specific category, or the number of missing documents recovered (that would otherwise have generated an NTF). The reporting features of a modern eTMF system, like Montrium’s eTMF Connect, are your best tool for the efficient development and tracking of meaningful metrics describing NTF generation and NTF-provoking TMF quality issues.
3. Cultural Shift
Gaining mastery over the note to file isn’t just about metrics. After all, your new NTF mission statement isn’t principally an analytical artifact—it’s mostly a social and emotional one. TMF leaders, in addition to creating and monitoring actionable NTF metrics, must lead by example. This means proposing solutions to TMF problems that encourage your team to spearhead necessary TMF change and supporting your team to and through those changes. It’s the responsibility of leadership to ensure that all team members are supported when taking positive risks.
Not every initiative to reduce NTF generation will be successful, but success on this journey depends on the mutual belief that all effort toward improvement is preferable to the NTF status-quo. Slow, incremental improvement is both praiseworthy and sustainable.
Final thoughts on the note to file in clinical research
It’s my sincere belief that the root cause of the overreliance of NTFs in the TMF is fear. It could be fear of change, fear of falling behind, fear of inspection findings, or fear of unrealistic expectations, just to name a few. Fear, however, is a massive obstacle to our TMF goals and the greatest saboteur of process improvement, especially when the desire to avoid fear supplants the mission of achieving TMF health.
While I think it’s naïve to strive for zero NTFs, I also believe in the power and importance of the narrative within each TMF. If you share this value, it’s imperative to eliminate the NTF wherever possible. The few NTFs that remain should align with your core purpose, values, and goals. It’s the strength of your core purpose, values, and goals that give you the strength to face your fears and minimize the role of the NTF. But, regardless of your commitment to eliminate the NTF or your intention to write your own NTF mission statement, I have one simple request:
The next time you write a note to file, pause for a moment, and ask yourself, “Why?”
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