Hi - its Saturday and I am in work (of course!) pushing back the frontiers of science.
I've had numerous messages of agreement and support from people who just responded to me and not the list, but Mike's was copied to the list as well, so I will make a brief (just a joke!) response and a proposal.
I expect that in all walks of life there are purists and pragmatists and shades of opinion in between. However, our discipline (clinical biochemistry) is a scientific one. To get past the gatekeepers into our profession, trainees have to have good science A levels, good science degree, MSc, PhD before they embark on the MRCPath. During this process they should have picked up a pretty good concept of what science is - a search for testable, falsifiable 'truth' (with the usual caveats applied to that word) that is underpinned by the hypothetico-deductive method of enquiry leading to theory building and knowledge with predictive value.
Scientific principles must underpin clinical biochemistry, and since clinical biochemistry is all about finding 'things' that reveal the pathological process and which (used properly) can inform clinical decision making, the identification, characterisation and quantitation of these 'things' must also be based on scientific principles. That must surely be a 'given' and a cornerstone of our profession!
You seem to be saying that there are two worlds which are profession inhabits - the pure 'scientific' world (which is an abstract fantasy inhabited by metrology geeks like me) and the 'real' world where you can create an analyte, name it without knowing what it is, create a test for it without knowing what it is, standardise it without having any of it in the calibrants and produce numbers which purport to tell our customer clinicians and patients what is wrong with them and what treatment they should get, get papers published and (soon to come no doubt) published guidelines!!!
If you do this often enough, do you not degrade the value of and confidence in those analytes that we really do know how to measure and where we do this pretty well? How does the end user know which tests are analytical (defined analytes, traceable reference measurement system), comparative (method-dependent tests with arbitrary unitage standardised by consensus) or just made up? Where does this all end? Where does it sit in the post-Carter world where you can go into Tesco and get a diagnostic test? What would T Blair think now that he has 'seen the light' about the value of science in our society?
Are we just paying lip service to evidence based medicine and evidence based clinical biochemistry? Where does the science stop and 'clinical pragmatism' take over? Who decides? Who drives our agenda? Who educates our trainees about this? What is safe for patients? What would they think if they read your sentence
"a "measurement" can have clinical value even if we have not the remotest idea what we are measuring" ?
We need to debate this properly!
So at Focus 2008 in Birmingham, let's have a debate
"Clinical Biochemistry - Science or Black Art? Purists vs Pragmatists"
I'll speak on one side - you can speak on the other!! I might even write a poem!
Cheers
Jonathan
Dr Jonathan Middle
Deputy Director, UK NEQAS Birmingham
0121 414 7300, fax 0121 414 1179
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________________________________
From: Clinical biochemistry discussion list on behalf of Hallworth Mike (RLZ)
Sent: Fri 17/11/2006 16:28
To: [log in to unmask]
Subject: Re: IMA - what are we measuring?
OK, even though it's late on Friday and I'm really busy, here's a quick
response!
Jonathan writes:
"Is there not some basic scientific work to be done before we can make
assertions about 'IMA', what it is, how it gets modified, is it a single
entity which can be identified, purified, standardised, what else in serum
binds cobalt etc, before we assert to clinicians that an entity IMA exists,
we are measuring 'it' properly, and that its measurement is clinically
useful? "
Yes to all that, Jonathan, except for the last bit! The fact is, and I know
it irritates the heck out of the purists, a "measurement" can have clinical
value even if we have not the remotest idea what we are measuring. I fully
accept that there are dangers here, and that we will do much better when we
do have all the answers - but there are a lot of things, from CA125 -
defined by the Ab that measures it - to analogue free T4 back to (I suppose)
even PBI that have given useful clinical information even if they are not
fully metrologically valid. That's not an argument against metrological
accuracy. It's just a recognition that in the real world flawed information
may be better than no information at all.
Keep at it, Jonathan - because we need the purists. But we need pragmatists,
also.
Have a good weekend, all
Mike
-----Original Message-----
From: Jonathan G. Middle [mailto:[log in to unmask]]
Sent: 17 November 2006 16:13
To: [log in to unmask]
Subject: IMA - what are we measuring?
Hi
Oh dear - another metrology rant coming! Please feel free to skip!
A chance concatenation of events (ACB west midlands meeting yesterday -
Anne Dawnay gave a talk on Ischaemia-modified albumin (IMA) - and the
arrival of the November Annals on my desk today containing articles by Orla
Maguire et al and Bob Beetham et al on IMA) prompts me to wonder what it is
we think we are doing with this 'analyte'.
It apparently is being 'measured' by an 'albumin cobalt binding' test which
is 'standardised' using EDTA solutions. There is a burgeoning literature on
'IMA', we now have reference ranges and 'corrected IMA' to take into account
albumin concentration, recommendations for clinical use and the FDA has
approved it!
With my pedant metrologist hat on I was going increasingly ballistic whilst
reading Orla's article (especially the bit about the manufacturer's
'reference' method). I got to the last paragraph of the discussion which
has the caveat: "Some issues remain about the ACB assay itself: the exact
nature of the entity or entities the assay is measuring (sic) is not known
and the fact that the calibrant supplied with the kit is a chelating agent
(EDTA) rather than a known concentration of IMA." I breathed a sigh of
relief - sense at last which states my main concerns! However, the
paragraph goes on to say "Even with these uncertainties, the measurement
(sic) of IMA by the ACB assay may have a role in the evaluation of patients
with ACS ..."
Here is the rant ... ready?
In order to measure something you have to have a standard which is traceable
back to the definition of the measurand - preferably in SI units. This
assay does not 'measure' IMA (whatever that is) - it measures the remaining
dithiothreitol cobalt binding capacity after interaction with a serum
sample. The standards mimic the 'albumin' cobalt binding by chelating
increasing amounts of the added cobalt.
Is it only me that worries about this? Is there not some basic scientific
work to be done before we can make assertions about 'IMA', what it is, how
it gets modified, is it a single entity which can be identified, purified,
standardised, what else in serum binds cobalt etc, before we assert to
clinicians that an entity IMA exists, we are measuring 'it' properly, and
that its measurement is clinically useful?
If you agree with me, please send something in support. Or if you have a
convincing argument that disposes of mine, please lets hear it!
Maybe I should start a new list - [log in to unmask] Then I
needn't disturb anyone else!
Not entirely ironically,
Jonathan
PS ... By the way, are the IMA 'units' in Bob's article on the effect of
storage at -20, the 'same' as the IMA 'kilounits' in Orlas's? Samples seem
to have the same numerical values and the method appears to be the same.
Dr Jonathan Middle
Deputy Director, UK NEQAS Birmingham
0121 414 7300, fax 0121 414 1179
-----------------------------------------------
Please use [log in to unmask] for PERSONAL work-related email Please use
[log in to unmask] for UK NEQAS service-related email For
work-unrelated personal email please ask for my private Gmail address
-----------------------------------------------
All opinions expressed in this email are mine alone and are not necessarily
representative of the views of the UK NEQAS organisation, UK NEQAS
Birmingham (Wolfson EQA Laboratory), University Hospital Birmingham NHS
Foundation Trust or University of Birmingham.
------------------------------------------------
The content of this message may be confidential and legally priviledged. If
you receive it in error please delete it immediately from your system.
Thank you.
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