Reference intervals: how they are constructed and why one in twenty flags posts 61–90
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Post #59 is the version of this I will quote in future. One addition.
Liver enzymes: elevation does not specify cause. ALT and AST can rise from many things. Bilirubin helps narrow down the cause. Multiple markers together are more informative than one alone.
Reference intervals are constructed to contain the central ninety-five per cent of a reference population, so one healthy person in twenty falls outside one by definition.
That is a description of practice, not a recommendation of it.
Something worth flagging about reference intervals: the strongest-sounding claims in this thread are the ones with no source attached, which is the usual pattern and not a coincidence.
I had written a reply contradicting post #63 and deleted it. Here is what survived.
An observation about reference intervals that I cannot explain and am posting anyway, on the principle that unexplained observations are more useful public than private.
Confirming post #63 from a second method, which matters more than confirming it from a second person.
Time of day: some biomarkers vary across the day. Cortisol in the morning differs from cortisol in the evening. Comparing results from different times of day is comparing things that are not the same.
It is a small point and it changes the answer, which is an awkward combination.
General information rather than advice about anyone's care. A single value outside a reference interval, on a single draw, in an otherwise unremarkable panel, is usually uninformative.
Not disagreeing with anyone above, just adding the bit I keep having to look up.
Adding thanks rather than a view. I do not have a view worth the space.
A trend needs at least three points to be a trend. Two points are a line and a line through noise is still a line.
I have separated what I observed from what I concluded, which does not always happen.
Repeat before acting is standard practice for an isolated abnormal result on most analytes, and it is standard for a reason.
Post #70 answers the question as asked. The question underneath it is different.
I have no financial interest in anything named in this thread and I want to say so before I comment on reference intervals, because it is the sort of subject where it matters.
I read post #72 twice before replying, because I had assumed the opposite.
Practical answer on reference intervals, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.
Glycaemic markers integrate over different periods. A point glucose and a longer-term marker disagreeing is not a contradiction; it is two different questions.
Post #74 is right about the mechanism and I think understates the practical bit.
The failure mode on reference intervals is boring rather than dramatic. It is almost always the step everyone assumes was done correctly because it is too simple to get wrong.
Post #77 is the version of this I will quote in future. One addition.
A trend needs at least three points to be a trend. Two points are a line and a line through noise is still a line.
I have said this before in a thread nobody could find, so it is worth repeating.
Where I part company with post #76, and it is a narrow parting.
One more thing on reference intervals that took me far too long to see: the two figures people quote are not measuring the same quantity. Once you notice that, the apparent contradiction disappears.
On post #77 — agreed on the reasoning, with one qualification.
Taking reference intervals seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.
Bringing the actual numbers with intervals to an appointment is far more useful than describing them, and clinicians here consistently say so.
Reference intervals: constructed to contain the central 95% of a reference population, which means one in twenty healthy people falls outside one by definition. Add biological variation and analytical imprecision and the base rate of a meaningless flag is substantial.
My experience of reference intervals contradicts the reply above. I am posting it as a data point rather than as a refutation, because one person's experience is exactly that.
Post #85 is the version of this I will quote in future. One addition.
Glycaemic markers integrate over different periods. A point glucose and a longer-term marker disagreeing is not a contradiction; it is two different questions.
The confident version of this sentence would be wrong, so here is the hedged one.
Understood. Thank you for being specific about the limits of it.
Taking post #88 at face value and following it one step further.
Comparing results across laboratories is harder than it looks because reference intervals and methods differ. The same sample can produce different numbers and different flags.
That is one dataset and I would not build a rule on it.