Standarization or Standarisation? Harmonization or Harmonisation? We seem to be headed toward a schism in performance specifications, rather than a consensus. Here's a current comparison of Global Performance Specifications for Chemistry Assays.

Consolidated Comparison of Chemistry Performance Specifications

Updated February 22, 2021
Sten Westgard

There are more and more performance specifications being generated today than there were in existence in the past. A proliferation of all of these goals can result in a lack of coherence in quality. One of the great changes to performance specifications was triggered at the Milan meeting of 2014, (which provided us the resulting consensus statement of 2015) where the authority over the "Ricos goals" was passed, from the informal group from the Spanish EQA societies,  over to the EFLM organization, where they are being more rigorously analyzed and organized. The EuBIVAC checklist, which promotes a standard protocol for biological variation studies, has spurred a new series of papers that have significantly re-stated the biological variation-derived analytical performance specifications. While some of those studies specifically calculated allowable analytical total error, others did not. Thus, this table below provides new information not reproduced elsewhere.

Rather than wait for the EFLM biological variation database to emerge with the latest studies integrated into the historical data from previous studies, we have opted to use just the latest data from those new EuBIVAS studies as definitive performance specifications.

Routine Chemistry Performance Specifications (allowable total analytical error, TEa)
Test or Analyte	CLIA	CLIA "2019"	2018 RIQAS SOTA	2014 Desirable "Ricos"	EFLM/ Desirable EuBIVAS	Rilibak	GOST 53133.1 2008 A1 (Russia)	China WS/T 403-2012	2015 "Spanish Min."
Alanine aminotransferase (ALT)	± 20%	± 15%	±14.9%	± 27.5%	±14.4%[a] ±19.51%[f]	± 21%	± 33%	± 16%	± 23%
Albumin	± 10%	unchanged	±9.1%	± 4.1%	±4.46%[f]	± 20%	± 9%	± 6%	± 14%
Alkaline phosphatase	± 30%	± 20%	±20.6%	± 12.0%	±10.7%[a] ±16.71%[f] (bone)	± 21%	± 27%	± 18%	± 31%
Amylase	± 30%	± 10%	±14.1%	± 14.6%	±13.7%[a] ±15.42%[f]		± 27%	± 15%	± 35%
Aspartate aminotransferase (AST)	± 20%	± 15%	±14.6%	± 16.7%	±13.4%[a] ±16.91%[f]	± 21%	± 22%	±  15%	± 21%
Bilirubin, direct			±29.4%	± 44.5%	±33.4%[b]
Bilirubin, total	± 0.4 mg/dL or ± 20% (greater)	± 20%	±16.6%	± 27%	±25.7%[b]	± 22%	± 33%	±  15%	± 24%
Blood gas p02	± 3 SD	± 15 mm Hg or ± 15% (greater)
Blood gas pCO2	± 5 mm Hg or ± 8% (greater)	unchanged		± 5.7%
Blood gas pH	± 0.04	unchanged		± 3.9%
Calcium, total	± 1.0 mg/dL	unchanged	±7.5%	± 2.5%	± 2.3%[b]	± 10%	± 7%	± 5%
Chloride	± 5%	unchanged	±4.6%	± 1.5%	± 1.2% [b] ± 1.71% [f]	± 8%	± 7%	± 4%	± 9%
Cholesterol, total	± 10%	unchanged	±8.6%	± 9.0%	± 9.3%[d] ±10.46%[f]	± 13%	± 16%	± 9%	± 11%
Cholesterol, HDL	± 30%	± 20%	±21.6%	± 11.6%	±11.1%[d] ±13.05%[f]				± 33%
Cholesterol, LDL		± 20%		± 11.9%	±11.3%[d] ±16.52%[f]
Creatine kinase	± 30%	± 20%	±11.3%	± 30.3%	±20.4%[a] ±27.67%[f]		± 44%	± 15%	± 24%
Creatine kinase isoenzymes	MB elevated (present or absent) or  ± 3 SD Creatinine	unchanged
Creatinine	± 0.3 mg/dL or ± 15% (greater)	± 0.2 mg/dL or ± 10% (greater)	±11.8%	± 8.9%	±6.4%[c] ±8.99%[f]	± 20%	± 18%	± 12%	± 20%
GGT		± 5 U/L or ± 15% (greater)	±14.1%	± 22.1%	±16.2%[a] ±21.96%[f]	± 21%	± 27%	± 11%	± 22%
Glucose	± 6 mg/dL or ± 10% (greater)	± 8.0%	±8.1%	± 7%	± 6.3%[e] ± 8.2%[f]	± 15	± 11%	± 7%	± 12%
HbA1c (NGSP)		± 10.0%			±2.8%[e] ±2.63%[e]
Iron, total	± 20%	± 15.0%	±9.9%	± 30.7%			± 29%	±  15%	± 24%
Lactate dehydrogenase (LDH)	± 20%	± 15.0%	±14.9%	± 11.4%	±7.7%[f]	± 18%	± 22%	± 11%	± 26%
LDH isoenzymes	LDH1/LDH2 (+ or -) or ± 30%
Lactate					±36.2%[e]
Lipase			±21.3%	± 37.9%	±12.6%[a] ±17.33%[f]	± 25%
Magnesium	± 25%	± 15.0%	±10.2%	± 4.8%	±4%[b]	± 15%	± 13%	± 15%
Potassium	± 0.5 mmol/L	± 0.3 mmol/L	±5.4%	± 5.6%	±4.6%[b] ±6.24%[f]	± 8%	± 9%	± 6%	± 8%
Sodium	± 4 mmol/L	unchanged	±3.6%	± 0.7%	±0.86%[f]	± 5%	± 4%	± 4%	± 5%
Total protein	± 10%	± 8.0%	±8.2%	± 3.6%	±3.4%[b] ±4.35%[f]	± 10%	± 9%	±  5%	± 12%
Triglycerides	± 25%	± 15%	±13.2%	± 26%	±28%[d] ±33.84%[f]	± 16%	± 33%	± 14%	± 18%
Urea Nitrogen	± 2 mg/dL or ± 9% (greater)	unchanged	±11.1%	± 15.5%	±16.1%[b] ±22.49%[f]	± 21%	± 22%	± 8%	± 19%
Uric acid	± 17%	± 10%	±9.2%	± 12%	±10.6%[b]	± 13%	± 18%	± 12%	± 17%

This is not an exhaustive list of goals. Indeed, RCPA goals and other popular goals are available on other pages on the website here. But this gives an idea of the global range of goals. There are some large disparities, and we will use the rest of 2019 to explore the implications of these differences and the challenges that laboratory performance will face if we adopt all of the new EFLM specifications.

Here are the references for the EuBIVAS studies:

a. Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum, Carobene A, Roraas T, Solvik UO, et al, Clin Chem 63:6. 2018.

b. EuBIVAS: Within- and Between-Subject Biological Variation Data for Electrolytes, Lipids, Urea, Uric Acid, Total Protein, Total Bilirubin, Direct Bilirubin, and Glucose, Aarsand AK, Diaz-Garzon J, Fernandez-CAlle P et al, Clin Chem 64:9 2017

c. The EuBIVAS Project: Within- and Between-Subject Biological Variation Data for Serum Creatinine Using Enzymatic and Alkaline Picrate Methods and Implications for Monitoring, Carobene A, Marino I, Coskun A et al, Clin Chem 63:9. 2017 Estimates from Enzymatic methods used.

d. Biological variation data for lipid cardiovascular risk assessment biomarkers. A systematic review applying the biological variation data critical appraisal checklist (BIVAC), Diaz-Garzon J, Fernandez-CAlle P, Minchinel J et al Clin Chim Acta 495 (August 2019) 467-475.

e. Systematic review of the biological variation data for diabetes related analytes, Gonzalez-Lao E, Corte Z, Simon M et al, Clin Chim Acta 488 (January 2019) 61-67.

f. EFLM database, accessed 1/13/2020. accessed with SIMED assistance 2/22/21 https://biologicalvariation.eu/meta_calculations

[Thanks to Randox RIQAS for sharing their State of the Art (SOTA) goals from their monthly EQA program]

[Special thanks to Vladimir Procenko, for an informal English translation of the Russia GOST goals, of which Annex A is listed here, which represents the maximum allowable analytical error for a single measurement.]