Maybe it is worth reflecting on the circumstance that the FDA did clear DiviTum based on the assay showing a high negative predictive value - a high NPV.
Comments on the DiviTum FDA clearence, from the latest Biovica report:
"For progression within 30 days, the NPV is 96.7%. This means that 96.7% of patients with
DiviTum®TKa measurements below the assay clinical cutoff, did not experience disease progression within the next 30 days."
Source: https://storage.mfn.se/cbf83906-8ea5-41c7-91ef-b14c9d0bfbb8/q1-2022-2023-biovica-eng.pdf
In this case (DiviTum®TKa, as a tool for monitoring disease progression in post-menopausal women with hormone receptor positive metastatic breast cancer) the FDA have put focus on the negative predictive value. This may be interesting as it may indicate on how the FDA navigates between different parameters relating to TK1 - such as perhaps a balance between safety and effectiveness.
Personally I find the focus on the negative predictive value (NPV) interesting also from another viewpoint, as it seems to somewhat correlate with speculative ideas on how to potentially use the TK1 protein assay in a future general health screening situation.
Large screening studies in China have established a sTK1p cut-off level (above 2,0 pM) which identifies a group of healthy individuals that have an increased risk of developing malignant tumors later in life.
Source (sTK1p - large health screening study in China): https://pdfs.semanticscholar.org/1ea1/e31a83da01d46b71b5b030f45704d4485d54.pdf?_ga=2.144816945.423734788.1661929548-124806339.1661929548
This means that a healthy individual with a value above the cut-off will have an increased risk of developing cancer later in life.
Of course acute factors, like ongoing infections, must first be ruled out. But as early pre-cancer initially develops slowly during an extended period of time, the individual will have a long period, years, to try and adjust the sTK1p levels back to normal. Based on the early warning signs, the individual will have an opportunity to try and adjust important lifestyle habits - such as food, sleep, exercise, stress - which are important factors that, over time, have an impact on the overall health.
On the other hand, a level below the cut-off is an indication that the individual have a low risk profile for developing cancer later in life.
Of course there is a very important discussion of ethics on if, and how, to use such data. Personally though, I think it would be of great value to have the opportunity to try and adjust negative lifestyle factors early in life - if assessed relevant by myself and my professional medical advisor. And, as a parallell, this is exactly the way so many diabetic and pre-diabetic individuals, often successfully, adjust to declining health - through the “simple” changing of lifestyle habits.
Even though the development of cancer is extremely complex and depending partly on important genetic factors, there is also a relationship to such things as the energy metabolism within developing cancercells - and such lifestyle factors like smoking, heavy glucose intake, lack of exercise will be relevant and have an overall impact on the potential development of the cancer disease.
When speculating on sTK1p in general health screening - a key factor may, as I see it, be the importance of the negative predictive value that indicates low risk.
Even though the sTK1p high value would be a clear risk factor (showing unusual cellproliferation and indicating further efforts in trying to find the source of the rising levels) this situation involves a significant amount of clinical uncertainty - what is the exact source of the rising levels?
On the other hand - the sTK1p low level (below 2,0 pM) would, in contrast, be a relevant and much safer parameter, as this is a clear clinical sign showing that no abnormal proliferation is ongoing in the individual.
And - as I see it - this may be an interesting parallell to the clearence of DiviTum, as it somewhat seems to relate to the approach from the FDA. The importance of the negative predictive value is highlighted in both cases.
Surely there is an enormous amount of future resources that society could potentially save, and instead use in other important areas of society, just depending on getting the overall population healthier.
Increased overall health in the population will, sooner or later, be one of the big and important issues for society - and, putting ethic discussions aside, my take is that simple regular annual TK1-testing would significantly help and render an overall healthier population. No question in my mind about that.
