Thanks.

The point I am making relates to critical care research wherein outcome measurements are often surrogates such as sums of scores responsive to a plurality of threshold breaches. (eg SOFA). This also relates to the standard criteria for the condition which may also be derived from a surrogate measure, as it is for example with sepsis 3 (SOFA of delta 2 plus suspician of infection).

I think statiticians and trialists forget that standard scoring (SOFA. SIRS) are actually measurements. Both are from the 90s so they have developed âgold standardâ status. They appear be accepted as above analysis by the statistician and trialist, like mortality itself.

Yet nonreproducibilty is the hallmark of critical care research. There has even been a recent call by NIH suggesting that perhaps funding for RCT for sepsis should be paused because virtually all are nonreproducible over the past 3 decades.

There is a test for nonreproducibility which I call detection of mathematical discontinuity. Here we see the measurement defining the condition under test, the statistical math, and the measurement defining the outcome as a single mathematical process. Any one step of that process can comprise the discontinuity, ie the source of nonreproducibility.

For 30 years statiticians have applied complex statistical functions to measurements derived of simple threshold breaches. The discontinuity would have been clear if the entire formulae set, had been written out on a single line.

This is a type of hidden stuctural bias. It affects all the trials but is entirely undetected by even the most brilliant and diligent.

Imagine a scale which is assumed by all to be the standard and above analysis. However the measurements of the scale change with the temperature. Of course it is obvious the entire math which incorporates outputs of this scale (including the statistical portion) will render non reproducible results because temperature is not included in the formula. However an entire group of diligent scientists could could use this tool for 3O years rendering nonreproducible results if the scale itself was considered THE standard.

In the critical search for the cause of nonreproducibility there are no standards which can be assumed to be ground truth.

âDo not try and bend the spoon, thatâs impossible. Instead, only try to realize the truthâŚthere is no spoon.â

The Matrix