Tools, Technologies and Training for Healthcare Laboratories

13 of 17 assays on a Roche Cobas 6000 c501 cannot hit preferred measurement uncertainty goals

A recent study of Roche Cobas 6000 c501 chemistry assays looks at their measurement uncertainty. We compare the Roche mu against the EFLM MAU and preferred permissible uncertainties proposed by the leading authorities on mu.

13 out of 17 assays on a Roche Cobas 6000 c501 cannot meet preferred measurement uncertainty goals

February 2023
Sten Westgard, MS

The burgeoning field of measurement uncertainty performance specifications has spawned a corresponding spree of publications. Now that we have the goals for measurement uncertainty, more and more papers are holding today's instruments to the new standards.

The most recent paper to do so is

Calculation of Measurement Uncertainty of 20 Clinical Chemistry Analytes According to the Practical ISO approach, Abdulkadir Car, Kamil Taha Ucar, Acibadem Univ. Saglik Bilim. Derg. 2023;14(1):1-9

This study is quite thorough in its calculation of measurement uncertainty, in that it doesn't rely only on an intermediate imprecision estimate alone for the estimate of measurement uncertainty (which is nevertheless laudable). Instead, as Panteghini has mandated, the uncertainty of the calibration must be combined with the uncertainty of the analytical method.

The sources for these measurement uncertainty performance specifications can be found in these references:

We will focus on just 19 of the 20 listed assays in the paper (the 20th, for ethanol, is troublesome because there are incomplete performance specifications for this analyte). The 2022 papers from Panteghini et al provide the definitive, preferred specifications for permissible uncertainy (pU, or as well will refer to them, PpU). Those specifications only cover 17 assays. The EFLM  database provides specifications for MAU, minimum and desirable, for all 19 analytes.

Roche Cobas 6000 c501
Level % Urel, relative
Expanded Uncertainty
EFLM minimum MAU Panteghini's pU (PpU)
Final verdict
Albumin 1 8.65% 3.8%

1.25%(des)
1.88%(min

Fails MAU and PpU
2 7.01% Fails MAU and PpU
ALT 1

8.29%

15.1% 4.65%(des)
6.98%(min)
Fails PpU,
passes min MAU 
2  6.36% passes min PpU,
passes min MAU 
Amylase 1 16.15% 9.9% 3.15% (des)
4.73% (min) 
Fails MAU and PpU
2 9.78% Fails MAU and PpU
AST 1 9.74% 14.4% 4.75% (des)
7.13% (min)
Fails MAU and PpU
2 7.03% passes min PpU,
passes min MAU
Bilirubin, Total 1 19.27%  30% 10.3% (des)
15.7% (min)
Fails Ppu
passes min MAU
 2 15.8% Fails Ppu
passes min MAU
CRP 1 22.98%  51.2%  3.76% (des)
5.64% (min)
 
Fails Ppu
passes min MAU
 2 10.04% Fails Ppu
passes min MAU
Fe (Iron)  1  10.33%  31%  none given  passes min MAU
 2  7.71%  passes min MAU
Glucose 1 10.4%  7.5% 2% (des)
3% (min)
 Fails MAU and PpU
2 4.2% Fails Ppu
passes min MAU
LDL-Cholesterol 1  8.9% 12.5%  none given passes min MAU
2  13.7% fails min MAU
HDL-Cholesterol 1  9.5%  8.7%  2.84% (des)
4.26% (min)
 Fails MAU and PpU
2  14.2%  Fails MAU and PpU
Cholesterol 1  7.9%  7.9%  3.0% (des)
7.0% (min)
Fails Ppu
passes min MAU
2  7.8% Fails Ppu
passes min MAU
Calcium 1 7.52% 2.7% 0.91% (des)
1.36% (min)
 Fails MAU and PpU
2  5.83%  Fails MAU and PpU
Chloride 1  6.41% 1.7% 0.49% (des)
0.74% (min)
Fails MAU and PpU
2 4.52% Fails MAU and PpU
Creatinine 1 11.9%  6.8%  2.2% (des)
3.3% (min) 
Fails MAU and PpU
2 7.6% Fails MAU and PpU
Potassium 1  6.02%  6.1%  1.96% (des)
2.94% (min)
Fails MAU and PpU
2  3.7% Fails PpU,
passes min MAU
Protein, Total 1  9.7%  3.9% 1.3% (des)
1.95% (min)
Fails MAU and PpU 
2 8.5% Fails MAU and PpU
Sodium 1 4.92% 0.8% 0.27% Fails MAU and PpU
2  3.58% Fails MAU and PpU
Triglycerides 1 6.3% 30% 9.9% (des)
14.9% (min) 
Passes PpU and min MAU  
2 5.7% Passes PpU and min MAU
Urea Nitrogen 1 8.06% 20.9% 9.9% (des)
14.9% (min) 
Passes PpU and min MAU
2 6.9% Passes PpU and min MAU

If we judge these assays by the PpU goals alone, we only have 17 assays, and for 13 assays, there is complete failure at both levels to achieve them. A 76% failure rate for the Roche Cobas 6000 is not encouraging.

If we judge these assays by whether or not both levels can achieve PpU goals, the failure rate grows larger still, to 88% failure.

If we judge these assays by the EFLM minimum MAU, then 7 of 19 assays pass. That is, 8 of 19 assays completely fail to meet MAU, a 42% failure rate. If we include assays that partially fail MAU, that error rate rises to 12 of 19, or 63%

Clearly, these new measurement uncertainty performance standards are harsh, perhaps impractically harsh, beyond the capability of even the most advanced instrument as a Cobas 6000. That should raise concerns about the promulgation and mandatory implementation of these new goals throughout the world.