Posted by Sten Westgard, MS
We've just seen probably the most important publication since the Milan Consensus was issued in 2014-2015.
It's a paper that significantly restates the goals for imprecision, bias, and allowable total error based on a new biological variation study:
Clin Chem. 2017 Jun;63(6):1141-1150. doi: 10.1373/clinchem.2016.269811. Epub 2017 Apr 20.
Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum.
Carobene A1,2,
Røraas T3,
Sølvik UØ4,
Sylte MS5,
Sandberg S3,4,5,2,
Guerra E6,
Marino I6,
Jonker N7,2,
Barla G7,
Bartlett WA8,2,
Fernandez-Calle P9,2,
Díaz-Garzón J9,
Tosato F10,
Plebani M10,
Coşkun A11,2,
Serteser M11,
Unsal I11,
Ceriotti F6;
European Biological Variation Study of the EFLM Working Group on Biological Variation
If we just focus on the desirable allowable total error (TEa), we can see some significant tightening in the performance specifications:
| Test |
TEa - REVISED |
TEa - 2014 |
Reduction |
| ALT |
14.4 |
27.48 |
47.6% |
| AST |
13.4 |
16.69 |
19.7% |
| GGT |
15.7 |
22.11 |
29.0% |
| ALP |
10.7 |
12.04 |
11.1% |
| LDH |
7.7 |
11.4 |
32.5% |
| CK |
20.4 |
30.3 |
32.7% |
| AMY |
13.4 |
14.6 |
8.2% |
| LIP |
12.6 |
37.88 |
66.7% |
If we think for a moment what this means for manufacturers, it's a massive change. If you essentially cut the target in half, your current methods probably have to be re-engineered to meet this new level of performance.
Put a different way, these new goals may be more accurate, but far less applicable. More ideal, but less practical.
For years, there have been complaints that the Ricos goals were too large, that they overestimated the amount of allowable error. Indeed, even after these revisions, there will still be those who claim that we need to be even more demanding about assay performance than how the Ricos allowable total error goals are structured and implemented.
But if we shrink our goals down to the point where no method on the market can hit the target, what have we actually accomplished? We will have a perfect set of goals that are impossible to achieve. That may be helpful to research and design departments at the manufacturers when they contemplate their next generation of instruments, but for laboratories that are operating today, with today's methods, they face the prospect of either having to massively increase the amount of QC they run and effort they devote to QC, or they will need to switch to goals that are more achievable and practical for today's clinical use.
The phrase that comes to mind here is, Don't let the perfect be enemy of the good. An obsession with constructing the perfect performance specification may make for great papers and publications and conference lectures, but it may also have the practical effect of leaving laboratories struggling with goals they can't achieve and performance they can't change.
These revisions may represent the goals of the perfected future. But we may need a set of goals for our imperfect today.
