Quality Standards
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:
- EFLM database, accessed 11/26/2022. https://biologicalvariation.eu/meta_calculations
- Performance specifications for measurement uncertainty of common biochemical measurands according to Milan models, Federica Braga and Mauro Panteghini, CCLM 2021; 59(8):1362-1368.
- Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice. Braga F, Pasqualetti S, Borrillo F, Capoferri A, Chibireva M, Rovegno L, Panteghini M, CCLM 2022 https://doi.org/10.1515/cclm-2022-0806
- Redesigning the surveillance of in vitro diagnostic medical devices and of medical laboratory performance by quality control in the traceability era. Mauro Panteghini. CCLM 2022. https://www.degruyter.com/document/doi/10.1515/cclm-2022-1257/html
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) |
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.