A New Look at the Limits of Detection (LD), Quantification (LQ) and Power of Definition (PD)

Gautschi, K.; Keller, Bryan; Keller, H.; Pei, Peng-Xiang; Vonderschmitt, Dieter J.

doi:10.1515/cclm.1993.31.7.433

Cited by 12 publications

(20 citation statements)

References 13 publications

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“…Further publications have shown that this observation is also valid for other procedures (3). At each analyte concentration a specific imprecision must therefore be expected and general data cannot be given.…”

Section: Introductionmentioning

confidence: 89%

“…The calculation of the precision profile, the lower limit of quantification (LLQ), the limit of detection (LD) and the power of definition (PD) has been described previously (3). In short: the precision profile (CV versus analyte concentration) can be derived from the varianee function.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, the power of definition (PD) can be calculated for every interval of interest (3,5). The PD allows one to determine which differences in subsequent values represent significant (with.…”

Section: Introductionmentioning

confidence: 99%

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Sensitivity and Specificity of Cocaine Metabolite Screening in View of the Analytical Performance of a Fluorescence Polarisation Immunoassay

Hänseler¹,

Keller²

1994

CCLM

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Immunoassays for drug screening are called 'qualitative' or 'semiquantitative' by the manufacturers of these tests and they urgently recommend the user to verify each result exceeding the recommended cut-off value by a confirmation test. For therapeutic drug monitoring assays or for the determination of tumour markers or hormones, similar recommendations are not given, although the same analytical technologies are used for these assays.A scientific validation of the commonly used cut-off values recommended by the official bodies (e. g. NIDA, DoD) is unfortunately not described in the accessible scientific literature.A solution to this problem was sought by evaluating the analytical characteristics of the assay and determining the diagnostic validity of the test using an immunoassay for the cocaine metabolite äs an example.Hundred urine samples frorn people suspected of cocaine abuse and 50 urine samples from patients unlikely to have consumed cocaine were analysed in triplicate with a commercially available fluorescence Polarisation immunoassay. From this data we assessed the analytical variance of the assay using the Computer program of Sadler & Smith (Clin. Chem. 36 (1990), 1346-1350). Using the functions provided, we calculated the limit of detection (LD) and the lower limit of quantification (LLQ) äs well äs the so-called power of defmition (PD) using a recently published method (Gautschi et a!., this Journal 31 (1993), 433-440). This procedure is mathematically well defmed, uses no artificial Standards or calibrators and is in compliance with IFCC recommendations.A clearly defined assessment of the diagnostic performance of an assay is of utmost importance for the discussion of adequate decision levels. The influence of different decision levels was demonstrated by assessing the diagnostic performance of the FPIA assay for benzoylecgonine by calculating the predictive values of a negative and positive test result for four different decision limits (12, 40, 150, recommended by DoD and 300 g/l, recommended by NIDA). The respeetive predictive values of the negative results were 0.931, 0.864, 0.704 and 0.661. The predictive value of a positive test result was uniformly 1.0 for all four cut-offs.These results are critically discussed wjth respect to the analytical performance of the assay, the socio-economic and legal consequences of the screening procedure.

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Section: Introductionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Sensitivity and Specificity of Cocaine Metabolite Screening in View of the Analytical Performance of a Fluorescence Polarisation Immunoassay

Hänseler¹,

Keller²

1994

CCLM

Self Cite

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“…10 " 13 Using the computer program by Sadler and Smith, 14 the variance was calculated for each triplicate measurement and the variance profile was constructed out of the individual variances. The parameters of the variance function were defined by an iterative procedure.…”

Section: Methodsmentioning

confidence: 99%

“…10 By setting the platelet number to "zero" in the variance function, the ]. This standard deviation was used to construct a normal distribution representing the random error of the blank (ie, the background noise of the instrumental system).…”

Section: Methodsmentioning

confidence: 99%

Estimation of the Lower Limits of Manual and Automated Platelet Counting

1996

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Most evaluators of automated or manual methods for platelet counting focus on characteristics such as imprecision, linearity, and carry over. The limits of the analytical procedure are usually not assessed. The limits of the different techniques are neither discussed in the literature nor do manufacturers of analytical systems supply these data.A new procedure is presented to assess the performance of the manual as well as the automated platelet count. This procedure allows, with defined statistical confidence (eg, 95%), the determination of (1) the limit of platelet detection (LD) at which signals of platelets can be discriminated from the system noise; (2) the lower limit of quantification (LLQ), at which a certain imprecision is not surpassed; and (3) the The determination of the number of leukocytes, erythrocytes, and platelets in blood is of great importance in many diagnostic processes. Two analytical procedures are commonly used for blood cell counting: the manual and the automated count. Manual methods for cell counting are known to be time consuming and tedious. 1It is common knowledge that manual cell counting is burdened with high imprecision.2 Nevertheless, these techniques are still used as routine methods in the laboratories of many practitioners or if low or high cell count ranges or atypical cells are present also in specialized hematology laboratories.The introduction of electronic cell counters permit a more precise enumeration of erythrocytes, leukocytes, and platelets and has reduced these drawbacks significantly. Coefficients of variation (CV) <3% can be obtained. 3 The precision and accuracy of electronic cell counters is better compared to manual counting mainly because a much higher number of cells is counted.2 This fact might lead to the assumption that this superior performance can be observed over the entire measuring range. Few authors have stressed the fact that this assumption is valid only for a limited measuring interval. 4 In the past, neither the LD nor the LLQ have been determined. When describing the analytical performance of an instrument, manufacturers of cell counters and evaluators of new instruments pay much attention to international committee recommendations.5 These include issues such as linearity, imprecision, and carry over, 67 but only a few authors ask what the limits of cell counting are at various platelet count levels. 6,8 At low platelet numbers, because fewer cells are counted, observed CVs are expected to be increased and even the use of automated cell counters may be inappropriate.5 For very high cell numbers, it is mainly the inaccuracy of the cell count that has to be critically evaluated. It is common practice to use manual counting methods if platelet numbers are low. The decision to use manual rather than electronic counting is based more on subjective impressions than on a solid statistical basis. In 1986, Hackney and coworkers 9 pointed out that there is a need for improvement in instrument and kit evaluations and stated that in contrast to clinical c...

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Standardized flow cytometric method for the accurate determination of platelet counts in patients with severe thrombocytopenia

Kunz

Höffkes

Kunz³

et al. 2000

Cytometry

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Background: The therapeutic option of prophylactic platelet (PLT) transfusion in cases of severe thrombocytopenia critically depends on the availability of accurate and precise counts because clinical decisions are widely based on decision or trigger points. Although often applied in current practice at a level of 20 Gpt/L, there is increasing evidence that the trigger points could safely be reduced to10 or even 5 Gpt/L. In order to facilitate this downward revision, it is necessary to have PLT counting methods that are able to provide reliable results in the appropriate decision range. Methods: Postchemotherapy‐induced pancytopenia PLT counting was performed in patients with hematological malignant disorders. This study describes a novel flow cytometric method that utilizes a PLT‐specific monoclonal antibody (CD41a) in conjunction with fluorescent reference beads in order to derive absolute platelet numbers. Results: Applying a mathematical model, this flow cytometric method was shown to have a detection limit of 0.24 Gpt/L and a lower limit of quantification (coefficient of variation [CV] = 10%) of 1.1 Gpt/L. These values are a substantial improvement on previously reported results for the Technicon H1 automated instrument or manual hemocytometry. Moreover, although the flow cytometry and Technicon H3 methods were found by supplementary analyses to show a reasonably good correlation, the hematology instrument showed a distinct tendency to overestimate PLT counts at low levels. Conclusion: It is proposed that this standardized immunoplatelet method offers the best approach in evaluating, at the clinical level, the possibility of lower PLT transfusion triggers. It can be used to evaluate the performance limitations of automated hematology analyzers that are widely used at the present time. Cytometry (Comm. Clin. Cytometry) 42:284–289, 2000. © 2000 Wiley‐Liss, Inc.

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A New Look at the Limits of Detection (LD), Quantification (LQ) and Power of Definition (PD)

Cited by 12 publications

References 13 publications

Sensitivity and Specificity of Cocaine Metabolite Screening in View of the Analytical Performance of a Fluorescence Polarisation Immunoassay

Sensitivity and Specificity of Cocaine Metabolite Screening in View of the Analytical Performance of a Fluorescence Polarisation Immunoassay

Estimation of the Lower Limits of Manual and Automated Platelet Counting

Standardized flow cytometric method for the accurate determination of platelet counts in patients with severe thrombocytopenia

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