Instrument bias repeatability

In cases where standardized methods are used in clinical laboratories to indicate bias, repeatability, or sensitivity, (for instance in enzymatic determinations) the measurement result is traceable to a reference method only if all the instruments involved in the method are appropriately calibrated against the proper physical standard. 

There is no bias inherent in BRDF. BRDF is a number derived from the ratio of physical parameters that can be specified in absolute units. However, individual laboratories may have measurement errors that lead to systematic offsets, such as an inaccurately measured solid angle. Other possible mechanisms are discussed in Ref. (8). It is not possible at this time to separate these systematic errors from bias however, intralaboratory measurements on the same instrument typically repeat within 5% (10). 

The bias error is a quantity that gives the total systematic error of a measuring instrument under defined conditions. As mentioned earlier, the bias should be minimized by calibration. The repeatability error consists of the confidence limits of a single measurement under certain conditions. The mac-curacy or error of indication is the total error of the instrument, including the... 

Note that z can be larger than the number of objects, n, if for instance repeated CV or bootstrap has been applied. The bias is the arithmetic mean of the prediction errors and should be near zero however, a systematic error (a nonzero bias) may appear if, for instance, a calibration model is applied to data that have been produced by another instrument. In the case of a normal distribution, about 95% of the prediction errors are within the tolerance interval 2 SEP. The measure SEP and the tolerance interval are given in the units of v, and are therefore most useful for model applications. 

The study of the precision of a method is often the most time and resource consuming part of a method validation program, particularly for methods that are developed for multiple users. The precision is a measure of the random bias of the method. It has contributions fi om the repeatability of various steps in the analytical method, such as sample preparation and sample injection for HPLC [5-9], and from reproducibility of the whole analytical method fiom analyst to analyst, fiom instrument to instrument and fiom laboratory to laboratory. As a reproducibility study requires a large commitment of time and resources it is reasonable to ensure the overall ruggedness of the method before it is embarked upon. 

One source of prediction error is the inherent accuracy and precision of the reference analytical method used. If the reference method produces erroneous values that are consistently high or low, this bias will be reflected in the prediction results. Other sources of prediction error relate to the reproducibility, stability, and repeatability of the NIR instrument. Reproducibility (precision) is validated by making repeated measurements of the same sample and removing it between runs. Small changes in conditions may occur owing to multiple insertions of a sample onto the instrument. Stability refers to similar changes that may occur over... 

The third approach is to use experimental methods to assess the error structure. Independent identification of error structure is the preferred approach, but even minor nonstationarity between repeated measurements introduces a significant bias error in the estimation of the stocheistic variance. Dygas emd Breiter report on the use of intermediate results from a frequency-response analyzer to estimate the variance of real and imaginary components of the impedance. Their approach allows assessment of the variance of the stochastic component without the need for replicate experiments. The drawback is that their approach cannot be used to assess bias errors and is specific to a particular commercial impedance instrumentation. Van Gheem et have proposed a structured multi-sine... 

Precision Instrument repeatability - ten replicate injections. RSD<1% Intra-assay precision. Multiple analysis of aliquots of a sample during one day. RSD < 2% Intermediate precision. Multiple analysts, instruments, days in one laboratory. Reproducibility by inter-laboratory studies to detect bias. 

Using appropriate ions of the natural analyte and the spike, the isotope amount ratios for the spiked sample and the spiked calibration standard are determined. It is suggested that alternating measurements of the isotope amount ratio are made on these two solutions (repeated measurement of the calibration blend allows mass bias correction to be performed for inorganic IDMS (see Section 3 10), repeating each five times. The mean value of the five measurements will minimise the effects of any instrument drift. An improved estimate of the natural analyte concentration in the sample can then be calculated from the data. 

The performance of measurement systems has been traditionally defined in terms of accuracy and precision. Accuracy can be defined as a measure of how close a result is to the actual value and precision is thought of as the uncertainty of the result, which we could identify with the standard uncertainty. Modem usage in the context of quality of analytical results tends to avoid these terms. This is because there has been a more fundamental appreciation of the actual measurement process. For example, accuracy or, perhaps we should say, inaccuracy, involves bias within a measurement process as well as statistically determined factors that cause the result to be different from the true result What, at one time, we would have blithely termed precision is now discussed as repeatability, the variability of a method when applied to measurements on a single sample within a laboratory, and reproducibility, which applies to measurements of that sample when appUed by different laboratories using different instruments operated by different operators. 

Figure 10.10 Comparison of Cd isotope ratio data obtained using different normalization procedures for repeated measurements of two terrestrial rocks samples and the Allende CVS chondrite (from [38]). (a) Comparison of results obtained by standard-sample bracketing and by external normalization (based on added Ag) using the empirical method of Marechal et al. [37], The bracketing approach yields inaccurate results for some samples, due to matrix-induced changes in instrumental mass bias, (b) Comparison of results obtained by external normalization using Ag using either the exponential law in combination with standard-sample bracketing or the empirical technique of Marechal et al. [37]. Both methods yield similar results for all samples. The isotopic data are shown as eCd/amu values, which denote the variation in Cd isotopic composition relative to a terrestrial standard and normalized to a mass difference of lu [38, 113].

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