Reference intervals: how they are constructed and why one in twenty flags posts 91–120
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
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.
Narrowing post #92, because the general version has more than one answer.
I changed my mind about reference intervals after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens.
Everything in post #94 holds. The case it does not cover is the one I have.
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.
One more caveat and then I will stop qualifying: the sample selected itself.
Biological variation: the person-to-person variation in a biomarker for a healthy person is larger than most people realize. Comparing your result to the reference interval is one thing; comparing your result today to your result from months ago is more sensitive to change.
The strongest argument against my own position on reference intervals, stated as well as I can state it, since nobody else has yet.
Post #99 answers the question as asked. The question underneath it is different.
Repeat before acting is standard practice for an isolated abnormal result on most analytes, and it is standard for a reason.
The mechanism is plausible, which is not the same as established.
I read post #100 twice before replying, because I had assumed the opposite.
If you are new and reading this thread for the answer to reference intervals: the answer is conditional, the conditions are in the third reply, and the rest of the thread is worth skipping.
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 arithmetic on reference intervals is the easy part and it is where the errors are, which is an uncomfortable combination. Show your working and someone will catch it.
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.
Coming back to post #104, because the follow-up matters more than the original answer.
Worth stating the null on reference intervals before we explain it: the observation may be nothing. That possibility deserves a sentence and usually does not get one.
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.
What I would want before treating reference intervals as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.
Fine by me. I had wanted a stronger conclusion and there is not one available.
Building on post #111 rather than restating it.
Reading back through the reference intervals threads from last year, the same three questions come up every time and only one of them has ever been answered properly. That seems like a documentation gap rather than a knowledge gap.
Everything in post #111 holds. The case it does not cover is the one I have.
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.
One of those cases where knowing the mechanism does not help the decision.
Biological variation: the person-to-person variation in a biomarker for a healthy person is larger than most people realize. Comparing your result to the reference interval is one thing; comparing your result today to your result from months ago is more sensitive to change.
I would treat that as a working assumption and revisit it.
If someone has run reference intervals properly I would rather read that than my own reconstruction of it. Posting mine only because the thread has gone quiet.
Taking post #115 at face value and following it one step further.
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.
Same experience here, different supplier, so it is at least not unique to one of them.
The confident answers on reference intervals and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.
Suggested topics
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
[2026 update] Lipid changes during rapid weight loss: the expected trajectory
Lipid changes during rapid weight loss: the expected trajectory Writing it up because I had to work it out twice and would rather nobody else did. Lipid changes during rapid weight keeps being re-asked here…
|
+51 | 56 | 7.1k | 17mo |
|
About the Bloodwork category
Panels, reference intervals, biological variation, and resisting the urge to over-read one result. This post is a community wiki: any member at trust level 3 or above can edit it, and every edit is recorded…
|
+4 | 8 | 4.4k | 3mo |
|
Second pass at: Fasting versus non-fasting and which tests care
On the subject in the title: Second pass at: Fasting versus non-fasting and which tests care Working notes rather than a conclusion. Posting a small dataset on Fasting versus non-fasting. It is mine, it is…
|
+20 | 25 | 21k | 3mo |
|
Lipase elevation without symptoms: the interpretation problem
Lipase elevation without symptoms: the interpretation problem Writing it up because I had to work it out twice and would rather nobody else did. Lipase elevation without symptoms — I have the observation and…
|
+21 | 25 | 62k | 5mo |
|
Biological variation versus analytical imprecision — does this still hold?
The question in the title: Biological variation versus analytical imprecision — does this still hold? I will give what I have already checked below so nobody repeats it. The question about Biological…
|
2 | 1.8k | 8mo |
Related topics — sharing the tags HbA1c, thyroid function, eGFR & renal function
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
Revisiting: Liver enzymes drifting down and what that usually means
On the subject in the title: Revisiting: Liver enzymes drifting down and what that usually means Working notes rather than a conclusion. A methods question rather than a substantive one, about Liver enzymes…
|
+55 | 61 | 39k | 3h |
|
Building a sensible monitoring schedule with your prescriber
Building a sensible monitoring schedule with your prescriber — setting out what I have, and where I think it stops being reliable. Building a sensible monitoring schedule — I have the observation and I do not…
|
+91 | 108 | 52k | 19mo |
|
Which panel is worth repeating and which is worth ignoring
The question in the title: Which panel is worth repeating and which is worth ignoring I will give what I have already checked below so nobody repeats it. An honest uncertainty about panel rather than a…
|
+125 | 133 | 17k | 10mo |
|
HbA1c lag and what it can and cannot tell you at eight weeks — one year on
Posting this under the heading it deserves: HbA1c lag and what it can and cannot tell you at eight weeks — one year on Everything below is what sits behind that. A methods question rather than a substantive…
|
+18 | 22 | 655 | 13h |
|
Which panel is worth repeating and which is worth ignoring — a second dataset
Asking directly, because I could not find a straight answer: Which panel is worth repeating and which is worth ignoring — a second dataset Posting a small dataset on panel. It is mine, it is uncontrolled, and…
|
+108 | 117 | 46k | 4mo |