Method performance studies

Within CEN TC 275, a distinct protocol for the conduct of inter-laboratory method validation trials is not selected or required, but it is recommended to apply ISO 5725 or the ISO/International Union for Pure and Applied Chemistry (lUPAC) harmonized protocol. " In the past, results of several national and international interlaboratory trials had been accepted. Nevertheless, the following fundamental aspects of the harmonized protocol for the design of method-performance studies should be fulfilled ... 

Even if most examples and procedures presented apply to in-house validation, the procedure does not distinguish between validations conducted in a single laboratory and those carried out within inter-laboratory method performance studies. A preference for inter-laboratory studies can be concluded from the statement that laboratories should always give priority to methods which have been tested in method performance studies. Within the procedure a profound overview of different categories of analytical methods according to the available documentation and previous external validation is given. For example, if a method is externally validated in a method performance study, it should be tested for trueness and precision only. On the other hand, a full validation is recommended for those methods which are published in the scientific literature without complete presentation of essential performance characteristics (Table 9). 

The method is externally validated in a method-performance study The method is externally validated but used on a new matrix or using a new instrument... 

Ph. Quevauviller, Methods Performance Studies for Speciation Analysis, The Royal Society of Chemistry, Cambridge (1998). 

Method performance study All laboratories follow the same written protocol and use the same test method to measure a quantity (usually concentration of an analyte) in sets of identical test samples. The results are used to estimate the performance characteristics of the method, which are usually within-laboratory- and between-laboratory precision and - if relevant - additional parameters such as sensitivity, limit of detection, recovery, and internal quality control parameters (IUPAC Orange Book [1997, 2000]). 

In a protocol about collaborative studies [10] it is also considered what is called preliminary estimates of precision. Among these the protocol defines the total within-laboratory standard deviation . This includes both the within-run or intra-assay variation (= repeatability) and the between-run or inter-assay variation. The latter means that one has measured on different days and preferably has used different calibration curves. It can be considered as a within-laboratory reproducibility. These estimates can be determined prior to an interlaboratory method performance study. The total within-laboratory standard deviation may be estimated fi-om ruggedness trials [10]. 

Use of Validated Methods In-Home Versus Interlaboratory Validation Wherever possible or practically achievable, a laboratory should use methods which have been fully validated through a collaborative trial, also called interlaboratory study or method performance study. Validation in collaborative studies is required for any new analytical method before it can be published as a standard method (see below). However, single-laboratory validation is a valuable source of data usable to demonstrate the fitness for purpose of an analytical method. In-house validation is of particular interest in cases where it is inconvenient or impossible for a laboratory to enter into or to organize itself a collaborative study [4,5]. 

TABLE 9 Differences between Method Performance Studies and Proficiency-Testing Schemes... 

Horwitz, W. (1995), Protocol for the design, conduct and interpretation of method performance studies, PureAppl. Chem., 67, 331-343. 

Another graphical description of the data is used when comparing the results of several trials is the box plot (also called box-and-whisker plot). A box represents the range of the middle 50% of the data, and whiskers extend to the maximum and minimum values. A line is drawn at the median value. A glance a this plot allows one to assess the symmetry and spread of the data. Figure 5.4 is a box plot for the carbonate data of figure 5.2. Specific plots, such as Youden two-sample plots for method performance studies, are discussed below. 

An interlaboratory bias study is a limited form of method performance study used to determine the bias of a standard method or the bias introduced by laboratories that use the standard method. Laboratories are chosen for their competence in performing the method, and the organization is the same as for a method performance study. The number of laboratories in the study is determined by the statistics required. If the bias (6) is calculated as the difference between accepted reference value and mean of n laboratories results, the significance can be tested using the standard deviation of the mean, sR/ /n. The Student s t statistic is calculated as... 

The ideal validated method would be the one that has progressed fully through a collaborative study in accordance with international protocols for the design, conduct, and interpretation of method performance studies. A typical study of a determinative method conducted in accordance with the internationally harmonized International Organization for Standardization (ISO)/International Union for Pure and Applied Chemistry (IUPAC)/AOAC International (AOAC) protocol would require a minimum of up to five test materials including blind replicates or split-level samples to assess within-laboratory repeatability parameters, and eight participating laboratories (15). Included with the intended use should be recommended performance criteria for accuracy, precision and recovery. 

The method is externally validated in a method-performance study... 

Improvement schemes can be defined as a succession of individual interlaboratory studies in which several laboratories analyse the same test samples for the same characteristics (usually the content of an analyte), following a similar protocol to validate each individual step of their own analytical method (Quevauviller, 1999a). They enable laboratories to develop and validate all steps of new or existing analytical procedure(s) in adequately organised successive exercises which may be considered as preliminary studies for laboratory or method performance studies or certification of RMs (Griepink and Stoeppler, 1992 Quevauviller, 1998b). Such programmes are particularly valuable in the case of speciation studies since the analytical procedures include several complex and critical steps. 

Full validation of an analytical method usually comprises an examination of its characteristics in interlaboratory method performance studies. However, before a method is subjected to validation by collaborative studies, the method must be validated by a single laboratory, usually by the laboratory that developed or modified this particular measurement procedure. Method validation can be described as the set of tests used to establish and document the performance characteristics of a method and against which it may be judged, thereby demonstrating that the method is fit for a particular analytical purpose. 

Material certification study Method performance study Proficieucy test Z Score... 

Method performance study - An interlaboratory study in which all laboratories follow the same written method to measure a quantity in sets of identical test samples. The reported results are used to estimate the performance characteristics of the method. ... 

Ph. Quevauviller, Method performance studies for inorganic analysis examples of results obtained by plasma spectrochemical techniques in the frame of Community Bureau of Reference (BCR)-certi-fication campaigns. J. Anal. At. Spectrom., 12 (1997), 871-879. 

Meanwhile, these effects are in no way included in the usual measures of accuracy as they result from a method-performance study in accordance with the accepted protocols [24, 25]. The accuracy experiment defined by ISO 5725 (Ref. 24, Part 1, Section 4) does not presuppose any variable matrix-dependent contribution, being... 

This interlaboratory study is a method performance study, not a study of the laboratory/analyst... 

From the above, it is demonstrated that organizing/participation in an interlaboratory method performance study is a useful exercise, which may be costly and time-consuming. Therefore it is important to realize that there is much potential benefit for ... 

Previous exercises have shown the difficulties of determining Hg in seawater. As an example, coefficients of variation of 26.7 and 11.6% between eleven laboratories (CV of the mean of laboratory means) were found for Hg levels of respectively 6.0 and 24.2 ng L [31]. Therefore, it was chosen to consider seawater samples containing much higher Hg concentrations (coastal seawater samples spiked with mercury) in a first method performance study and to use natural coastal seawater, along with a spiked sample, in the second interlaboratory study. 

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