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Measurements for 8 Common Analytes in Native Sera Identify Inadequate Standardization among 6 Routine Laboratory Assays
H.C.M. Stepman, U. Tiikkainen, D. Stöckl,
H.W. Vesper, S.H. Edwards, H. Laitinen, J. Pelanti,
L.M. Thienpont, and Participating Laboratories
June 2014
www.clinchem.org/content/60/6/855.full
© Copyright 2014 by the American Association for Clinical Chemistry
© Copyright 2009 by the American Association for Clinical Chemistry
IntroductionIntroduction
Proficiency Testing (PT), also known as External Quality Assessment (EQA), has earned a well-deserved position as an element of laboratory quality management
PT with commutable samples and high-quality targets is essential for assessing the accuracy of diagnostic assays and the interchangeability of generated results
The “intrinsic” quality of a manufacturer’s assay may be influenced by the laboratory using it; therefore, assessment under routine conditions is essential
See Editorial by Horowitz GL. Assessing Accuracy on the Front Lines: A Pragmatic Approach for Single-Donor Proficiency Testing. Clin Chem 2014
© Copyright 2009 by the American Association for Clinical Chemistry
QuestionsQuestions
What were the special aspects of the experimental design of the PT survey described?
How was the data assessment done? Quality indicators? Targets? Limits?
© Copyright 2009 by the American Association for Clinical Chemistry
Materials and Methods – Study DesignMaterials and Methods – Study Design
Use of 20 fresh-frozen single donation serum samples prepared according to CLSI C37-A
Selection of laboratories using “homogeneous tests” Reagent, calibrator, platform from the same manufacturer
Inclusion of assays installed on random access platforms
Abbott Architect, Beckman Coulter AU, Ortho Vitros, Roche Cobas, Siemens Advia, and Thermo Scientific Konelab
Measurement of 8 analytes Creatinine, glucose, phosphate, uric acid, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides
© Copyright 2009 by the American Association for Clinical Chemistry
Materials and Methods – Data AssessmentMaterials and Methods – Data Assessment
Quality indicators Intra-assay and combined imprecision (including sample
matrix interference) Bias and total error
Targets Peer group “All-method trimmed mean” (AMTM) Reference (REF) method values (cholesterol, creatinine,
uric acid)
Limits Reflecting state-of-the-art performance Related to biological variation
© Copyright 2009 by the American Association for Clinical Chemistry
QuestionsQuestions
What were the main findings of the study?
What were the limitations?
© Copyright 2009 by the American Association for Clinical Chemistry
Results – SummaryResults – Summary Excellent peer performance for most assays (except
HDL and LDL cholesterol)
Intrinsic quality sufficiently robust for satisfactory performance in a daily laboratory context
Considerable bias for some assays (Table 1/Figures 1 & 2)
Siemens Advia creatinine (-4.2%), Ortho Vitros phosphate (8.9%), Beckman Coulter AU triglycerides (5.4%) and LDL (15%), Thermo Scientific uric acid (6.4%)
More biases at low & high concentration
Inter-laboratory differences >30% (Table 2)
© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry
ResultsResults
Table 1. AMTM/REF bias estimates (at low, mid, and high concentration) for each assay (named by manufacturer). The blue, underlined values indicate violation of the limits. CHOL, cholesterol; CREA, creatinine; GLU, glucose; HDL, HDL cholesterol; LDL, LDL cholesterol; PHOS, phosphate; TRIGL, triglycerides; UA, uric acid; NA, not applicable.
CHOL CREA GLU HDL LDL PHOS TRIGL UABias Limit (%) 4 4 4.5 4.5 4.5 4.5 4.5 4Abbott 3.0 5.1 -0.4 5.5 2.7 0.1 2.5 -4.9 2.5 3.7 -0.2 -1.0 1.5 0.0 0.1 -1.2 2.3 2.8 0.2 -5.4 0.9 0.0 -1.0 1.9Beckman 2.7 -0.6 2.1 0.3 NA 0.8 5.8 -2.6 3.8 0.5 1.9 -3.2 NA 0.5 5.4 -1.3 4.4 1.1 1.6 -5.6 NA 0.4 5.3 -0.3Ortho -0.6 1.6 -3.0 0.0 NA 14.6 -0.9 -2.2 0.0 1.2 -2.8 -1.1 NA 8.9 -0.3 -2.6 0.4 0.9 -2.4 -1.9 NA 6.7 0.0 -2.8Roche 3.5 2.6 -0.7 -0.3 5.2 -1.1 0.0 -4.6 2.5 2.7 -0.6 3.9 2.0 -0.7 -1.6 -3.4 1.9 2.7 -0.6 6.7 0.4 -0.5 -2.3 -2.4Siemens 0.7 -5.5 1.2 2.8 0.0 1.3 0.3 0.4 0.0 -4.2 1.0 2.2 -0.3 1.1 0.7 0.8 -0.4 -3.4 0.5 1.7 -0.4 1.1 1.0 1.2Thermo Scientific 2.2 -1.5 0.8 -8.3 2.1 NA -1.9 5.2 2.6 -0.3 0.7 -0.7 -0.1 NA 1.0 6.4 2.8 0.5 0.6 4.4 -1.3 NA 2.3 7.3
© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry
Figure 1. Assay bias (% difference = (mean of peer group result - target value/target value)*100) and total error vs AMTM (glucose, HDL-cholesterol) or REF target values (cholesterol, creatinine). Abbott (red diamond), Beckman (blue square), Ortho (black triangle), Roche (yellow circle), Siemens (red square), and Thermo Scientific (blue diamond). The red-broken bias limits are those listed in Table 1; the blue-broken limits are optimal bias limits from biological variation (online Supplemental Table 6).
ResultsResults
For conversion of the traditional units to SI units used in the online Supplemental Figs., multiply by 0.02586 for cholesterol (mmol/L), 88.40 for creatinine (µmol/L), 0.05551 for glucose (mmol/L),and 0.02586 for HDL cholesterol (mmol/L).
-6
-4
-2
0
2
4
6
8
100 120 140 160 180 200 220 240
Ass
ay D
iffer
ence
(%)
Cholesterol REF (mg/dL)-10
-8
-6
-4
-2
0
2
4
6
8
0.5 0.7 0.9 1.1 1.3 1.5
Ass
ay D
iffer
ence
(%)
Creatinine REF (mg/dL)
-5
-4
-3
-2
-1
0
1
2
3
4
5
70 90 110 130 150 170 190
Ass
ay D
iffer
ence
(%)
Glucose AMTM (mg/dL)-15
-10
-5
0
5
10
15
20 30 40 50 60 70 80 90 100
Ass
ay D
iffer
ence
(%)
HDL-Cholesterol AMTM (mg/dL)
© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry
Figure 2. Assay bias (% difference) and total error vs AMTM (LDL cholesterol, phosphate, triglycerides) or REF target values (uric acid). Abbott (red diamond), Beckman (blue square), Ortho (black triangle), Roche (yellow circle), Siemens (red square), and Thermo Scientific (blue diamond). The red and blue broken limits are the same as described for Fig. 1.
ResultsResults
For conversion of the traditional units to SI units used in online Supplemental Figs., multiply by 0.02586 for LDL cholesterol, 0.3229 for phosphate (mmol/L), 0.01129 for triglycerides (mmol/L), and 59.48 for uric acid (µmol/L).
-20
-10
0
10
20
30
40
50 60 70 80 90 100 110 120 130 140 150 160
Ass
ay D
iffer
ence
(%)
LDL-Cholesterol AMTM (mg/dL)-5
-3
-1
1
3
5
7
9
11
13
15
2.3 2.6 2.9 3.2 3.5 3.8 4.1 4.4Ass
ay D
iffer
ence
(%)
Phosphate AMTM (mg/dL)
-15
-10
-5
0
5
10
15
20 70 120 170 220 270 320 370
Ass
ay D
iffer
ence
(%)
Triglyceride AMTM (mg/dL)-8
-6
-4
-2
0
2
4
6
8
10
3 4 5 6 7 8 9
Ass
ay D
iffer
ence
(%)
Uric Acid REF (mg/dL)
© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry
ResultsResults CHOL CREA GLU HDL LDL PHOS TRIGL UABias (%)Min -16 -9 -8 -20 -17 -6 -15 -7Max 6 17 6 8 25 13 13 11Diff 1 22 26 14 27 43 19 28 18Diff 2 11 22 10 16 25 14 21 16Diff 3 9 17 9 13 21 14 15 13Bias Low (%)Min -18 -10 -10 -16 -22 -8 -35 -7Max 6 28 6 14 42 21 29 14Diff 1 24 38 16 30 64 29 64 21Diff 2 12 36 12 22 52 22 38 18Diff 3 9 35 10 19 39 21 23 14Bias High (%)Min -15 -9 -6 -22 -15 -6 -14 -7Max 6 10 6 10 17 10 9 10Diff 1 21 19 12 32 32 16 23 17Diff 2 11 17 11 18 16 12 13 14Diff 3 9 16 8 18 14 11 11 13
Table 2. Observed AMTM bias in the participating laboratories. The blue, underlined values refer to maximum absolute laboratory biases >15% and differences between laboratories >30%. CHOL, cholesterol; CREA, creatinine; GLU, glucose; HDL, HDL cholesterol; LDL, LDL cholesterol; PHOS, phosphate; TRIGL, triglycerides; UA, uric acid; NA, not applicable. Diff 1, the difference between the most deviating laboratories, diff 2 and 3 the 2nd and 3rd most deviating laboratories. Note: “bias low and high” stand for the bias at the limits of the concentration range covered by the panel.
© Copyright 2009 by the American Association for Clinical Chemistry
Limitations of the studyLimitations of the study
The CLSI C37-A protocol does not in itself prove that the sampels were commutable
The number of laboratories included was, of necessity, relatively small
Concentration ranges covered by the samples were small; no reflection of performance at pathological concentrations
Targets traceable to reference methods not available for all analytes
Selected state-of the-art limits can be debated
© Copyright 2009 by the American Association for Clinical Chemistry
ConclusionsConclusions
The results indicated room for improved quality of performance, standardization and interchangeability of results
Notable was the observation that this applies for the simple analytes (and at concentrations) assessed here
The study demonstrated that dedicated PT surveys are a powerful tool to uncover and hopefully solve certain problems
Dedicated PT surveys do not substitute conventional PT but are complementary
© Copyright 2009 by the American Association for Clinical Chemistry
Final Comment in EditorialFinal Comment in Editorial
“For now, we should celebrate the insights that Stepman et al. have provided. As good as conventional PT may be, we can do better.”
“We are indebted to these authors for shedding light on a problem we may have assumed we did not have and, more important, for providing a powerful tool to help us make things better.”
Horowitz GL. Assessing Accuracy on the Front Lines: A Pragmatic Approach for Single-Donor Proficiency Testing. Clin Chem 2014.
© Copyright 2009 by the American Association for Clinical Chemistry
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