Stranger Things: 3 Monsters In Your TMF

The Netflix series Stranger Things is known for showcasing 80s’ films, pop culture, science fiction, and horror—all with a generous sprinkling of Dungeons and Dragons. Most of all, Stranger Things is known for its monsters: the Demogorgon, a demon with a mouth as its face; the Mind Flayer, a skyscraper-sized, spider-like monster comprised of darkness and shadow; and Venca, the scarred and distorted human turned undead wizard. Each of these monsters come from the same evil but threaten the heroes of Stranger Things in their own supernatural way. Their unnoticed rise, shocking reveal, and suspicious downfall punctuate each season and keep us engaged until the creepy conclusion.

Unfortunately, the monsters of Stranger Things have an equivalent in the world of the TMF: the note to file (or NTF). A note to file is a document, taking the form of a memo, filed in the TMF that attempts to explain a discrepancy in trial conduct. As we’ve discussed before, writing an NTF is almost always the wrong decision, as it commonly takes attention away from solving a TMF quality problem and often produces more regulatory risk than no action at all.

In other words, these NTFs introduce danger into your TMF like the Demogorgon imperils Hawkins and we bet there are at least a few monstrous NTFs in your TMF right now. Let’s take a closer look at these monsters in the TMF so that we have a fighting chance to return them to the Upside-Down—right where they belong.

The Demogorgon: The Ever-Growing NTF

The Demogorgon is a thoughtless predator ruled by a voracious appetite and is in constant pursuit of prey.

The same can be said for an NTF that keeps growing in scope, all while taking the place of your due diligence. This type of NTF usually has a list of dozens of impacted clinical trial sites or documents and attempts to address a systematic clinical operations or essential documentation quality issue. Sadly, this type of NTF is written too late to meaningfully impact a problem, especially a systematic one. To be a valid component of a TMF, the NTF must fully define the problem and provide a full narrative of the solution. NTFs rarely contain a complete narrative or sufficient evidence of due diligence activities because they are not designed to fill this role. In fact, most NTFs in this category act as a substitute for hard work or a distraction from corrective action and verification. All of this, of course, is better captured through a corrective and preventive action plan (CAPA) as part of an overall quality system.

The Mind Flayer: The Missing Document NTF

The Mind Flayer is a sentient entity intent on destroying the world from the shadows, just like your missing document NTF is bent on destroying the health of your TMF.

For all involved, the NTF is an unhappy compromise, especially in the case of a missing document. For TMF stakeholders looking to close out persistent missing document action items, writing a missing document NTF in the place of the absent document feels like the only reasonable step to take. Regrettably, the harsh reality is that no NTF, no matter how complete, can replace a missing document. The only remedy for missing documents is to prevent them from generating in the first place. This can be achieved through an ongoing cycle of TMF QC that continually verifies the condition of the TMF against predetermined TMF quality expectations. Reducing the latency between document generation and filing is your best defense against missing documents.

Venca: The Unnecessary NTF

Just as Venca preys on the weak and downtrodden, the unnecessary NTF preys on the unsupported and overwhelmed TMF stakeholder.

Writing an unnecessary NTF creates a metaphorical neon sign pointing regulators towards areas of weakness and concern. When weighing the risks and benefits of writing an NTF, consider that regardless of the quality of its content, the NTF will draw greater attention to that part of the TMF. Therefore, it’s always worth pausing to explore if another solution is more appropriate. In many cases, confidently following your existing TMF processes can be your guide to overcoming routine TMF challenges, all without planting red flags for regulators.  Remember, choosing not to write an NTF is always a viable option. Having confidence in your skills, your colleagues, and the narrative your TMF tells is your antidote to the unnecessary NTF.

The TMF tells the story of one of the most complex endeavors of humanity: the conduct of safe and ethical clinical research. We are all imperfect, and, as a result, our TMFs are bound to be imperfect as well. Although writing an NTF is generally a poor course of action, it’s naïve to dismiss them as entirely without purpose. Ultimately, it’s up to you to use your best judgment to prevent your NTFs from turning into the monsters they wish to be. In the event an NTF does go bad, however, it’s your duty to take up the weapons at your disposal, like TMF training, real-time TMF reporting, and the cycle of QC, and to confidently fight back. Your TMF is depending on you.