PENE will only be fully validated when there are objective techniques to measure it, and its able to be demonstrated to be a key feature of a large cohort, or distinctive subgroup within that cohort.
This comes down to what is meant by validation. If this were validated in the eyes of the medical community then the vast majority of doctors would already be using it. The very question of this thread would not even arise.
A consensus criteria like the ICC or CCC do not validate the content. The content would, ideally, if we had funding, be validated on large controlled cohorts. That hasn't happened as yet. Its been a major stumbling block for us. Things are not replicated, studies are not done to properly validate claims .... there are no resources available to do these things. Similarly any new IOM definition would not be validated. The closest we have to this are various papers by Jason.
ME is still controversial. The ICC is still controversial. Being controversial does not make something wrong, it means there is substantive disagreement.
The tests we can do, especially the 2 day CPET, leave very little room for controversy. Its a slam dunk win one way or another. Either someone believes there is a problem, or they are revealed as being contrary to the hard facts.
I can imagine the kinds of questions many doctors might have about PENE, and here we are talking about the defining characteristic of ME, either in its current incarnation or as post exertional malaise in older definitions. Please remember that most of these people have never experienced it. You or I have personal experience, they do not, and they quite rightly want evidence for complete validation. Please also consider that generations of patients have been convinced that their PENE is just chronic fatigue, and most doctors were too.
Can you measure it? In what units? How do we distinguish it from fatigue? In what units on what lab test? What scan? If you are willing to accept subjective questionnaires, then how were those questionnaires validated? How do we know the results of the questionnaire are not an artifact?
The 2 day CPET is part of this, and so is research by people like the Lights. CPET measures work capacity i.e. physical functional capacity. The 2 day CPET measures a crash in work capacity following exercise. The biochemical shifts post exercise measured by the Lights (and others) give further information. On a case by case basis every patient who has these can and should demand recognition and their rights, regardless of whether or not their ME or CFS or ME/CFS diagnoses are recognized. I think a similar argument can be made for other abnormalities, including severe NK cell dysfunction.
I do think the IOM is going to claim their view is validated. I make the distinction between a claim of validation and substantive validation.
It doesn't help that medicine does not have double standards - it has so many contradictory standards that I am almost surprised some doctors don't have their heads implode. I do not want to start arguing about psychobabble and evidence based medicine here however.
In the end validation comes down to sound justification. There are now strong ideas in the medical community about what that means. None of our diagnostic criteria meet those requirements. They probably could if we had more funding and resources, but we don't. They might if the CDC does its research properly for their new research criteria, but they refuse to use the most important test, the 2 day CPET. Even the CDC study though may require further validation if the results are not highly definitive. Worse we might find ourselves, yet again, in a fight to discredit another botched government study.