Within-laboratory variation

If repeatability is the only estimate of precision that is obtained, this is unlikely to be representative of the variability observed when the method is used over a long period of time. Intermediate precision is often more relevant - this expresses the within-laboratory variation or within-laboratory reproducibility (different days, different analysts, different equipment, etc.). This is initially obtained from validation studies and confirmed later by examining the results obtained for quality control material measured over a period of about three months (see the quality control (QC) charts in Chapter 6). 

The uncertainty of a measurement is always a very important consideration but it is especially so with durability tests. In addition to the basic physical test methods, there are the complications of exposure conditions, tests spanning long times and the process of extrapolating results to make predictions. The combination of these factors will inevitably lead to large uncertainties that can very easily be of such a magnitude that any conclusions are meaningless. Terms used to describe precision include repeatability, which refers to within laboratory variation and reproducibility, which refers to variation between laboratories. 

Intermediate precision (day-to-day Precision including within-laboratory variations, e.g., different... 

Intermediate precision includes within laboratories variations different days, different analysts, different equipment, etc. 

Precision is the degree of agreement between a series of measurements obtained from multiple sampling of the same homogeneous sample under prescribed conditions. Precision may be considered at three levels repeatability (precision under the same operating conditions over a short interval of time), intermediate precision (precision within-laboratory variations different days, different analysis, different equipment, etc.), and reproducibility (precision between laboratories, collaborative studies, usually applied to standardization of methodology). 

Intermediate Precision. Intermediate precision expresses within-laboratory variation and is generally performed on different days using different analysts, equipment, and sample preparations. This test may not be applicable if the laboratory has only one workstation. Additionally, this test may not be appropriate for automated workstations that are operating under the same environment and controls within a laboratory. This assumption is made on the basis that the automated workstations are identical (i.e., same configuration, same software and hardware) and that they have been suitably qualified and maintained to a consistent standard and operate under a similar climatic environment. The influence of the analyst is reduced to the preparation of solvents, and this should be covered by the robustness studies. 

Precision should be measured using a minimum of five determinations per concentration. A minimum of three concentrations in the range of expected concentrations is recommended. The precision determined at each concentration level should not exceed 15 % of the coefficient of variation (CV) except for the LLOQ, where it should not exceed 20 % of the CV. Precision is further subdivided into within-run, intrabatch precision or repeatability, which assesses precision during a single analytical run, and between-run, interbatch precision or reproducibility, which measures precision with time, and may involve different analysts, equipment, reagents, and laboratories. Since it is not always easy to obtain data about the reproducibility in the strict sense it often makes sense to use intermediate precision this expresses within-laboratories variations on different days, by different analysts, and on different equipment, etc. [60],... 

Intermediate precision6 Intermediate precision expresses within-laboratories variations different days, different analysts, different equipment, etc. This characteristic may be assessed on the worst-case surface(s) representing poor recovery and/or high variability +... 

Intermediate precision is the within laboratory variation over a long period of time. The standard deviation will be intermediate in value between that obtained under repeatability and that obtained under reproducibility conditions for similar samples using the same method. 

Intermediate precision expresses within-laboratory variations (usually on different days, different analysts and different equipment). If reproducibility is assessed, a measure of intermediate precision is not required. 

The geometric mean and the upper and the lower control limits are calculated from the results of examination of the first 20 RMs. Each RM is examined once. The 20 measurements are preferably done on different days and by different technicians to cover within-laboratory variations. The counts of these RMs should be plotted on a separate graph, in order to check whether these counts meet the criteria stated below (i.e. that the analytical process is under control). If the result of one or more of these 20 counts does not meet the criteria, the cause(s) for this should be identified and a decision made about the validity of the count(s). If the cause can be identified (assignable cause) then this count should be disregarded and the geometric mean and control limits recalculated from the remaining counts. If the cause cannot be found then the... 

Repeatability (within-laboratory variation). This is the precision of the procedure when repeated by the same analyst under the same set of conditions (same reagents, equipment, settings, and laboratory) and within a short interval of time. The repeatability of a procedure is assessed by carrying out complete, separate determinations on separate, identical samples of the same homogeneous batch of material and thus provides a measure of the precision of the procedure under normal operating conditions. 

Precision, which quantifies the variation between replicated measurements on test portions from the same sample material, is also an important consideration in determining when a residue in a sample should be considered to exceed a MRL or other regulatory action limit. Precision of a method is usually expressed in terms of the within-laboratory variation (repeatability) and the between-laboratory variability (reproducibility) when the method has been subjected to a multi-laboratory trial. For a single-laboratory method validation, precision should be determined from experiments conducted on different days, using a minimum of six different tissue pools, different reagent batches, preferably different equipment, and so on, and preferably by different analysts Repeatability of results when determined within a single laboratory but based on results from multiple analysts is termed intermediate precision Precision of a method is usually expressed as the standard deviation. Another useful term is relative standard deviation, or coefficient of variation (the standard deviation divided by the absolute value of the arithmetic mean result, multiplied by 100 and expressed as a percentage). 

Precision - integration, particularly at low sample amounts, may be difficult and an assessment of the precision of the experiment is needed. As alluded to above there are three levels of precision testing repeatability, intermediate precision and reproducibility. Repeatability expresses the precision under the same operating conditions over a short interval of time. This is frequently the only precision information provided in literature reports. Intermediate precision expresses within-laboratory variations across different days, different analysts, different equipment, etc. and it is a key indicator of how an assay will perform under real conditions. Reproducibility expresses the precision between laboratories and typically only becomes important if a method is transferred between laboratories - for example, from an R D site to a manufacturing facility. 

During the three sampling periods, blind duplicates of 28 samples were submitted for immunoassay analyses by a single laboratory as a quality-assurance measure. Results for the samples are summarized in table II. The maximum difference between duplicates was 0.5 ug/L and 86 percent of the samples had absolute differences of 0.14 ug/L or less. These results indicate that within-laboratory variation of the method is relatively small. 

The results show that within-laboratory variation is small and Indicate that within-laboratory precision can be very good. 

Between-laboratory variation was much larger than within-laboratory variation, but there was no apparent bias between the laboratories (Table II). About 20 percent of the between-laboratory differences... 

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