Experimental design ruggedness

The experimental design for ruggedness testing is balanced in that each factor level is paired an equal number of times with the upper case and lower case levels... 

Experimental Design for a Ruggedness Test Involving Seven Factors... 

To our knowledge, in the first approach described, Youden and Steiner introduced the term ruggedness test for a setup in which by means of an experimental design the influences of minor but deliberate and controlled changes in the method parameters or factors are evaluated in order to detect non-robust factors, i.e., with a large influence on the response. Controlling the latter factors avoids problems in the following interlaboratory study. 

Vander Heyden, Y., Luypaert, K., Hartmann, C., Massart, D. L., Hoogmartens, J., and De Beer, J. (1995). Ruggedness tests on the high-performance liquid chromatography assay of the United States Pharmacopeia XXII for tetracycline hydrochloride. A comparison of experimental designs and statistical interpretations. Anal. Chim. Acta 312, 245-262. 

A ruggedness test requires an experimental design approach. It consists of the following steps ... 

The ruggedness of a method can be tested using two types of experimental designs. Procedure related factors at the one hand are examined mainly in screening designs of the Plackett-Burman or... 

M. Mulholland, J. Waterhouse, Investigation of the limitations of saturated fractional factorial experimental designs, with confounding effects for an HPLC ruggedness test, Chromatographia, 25 (1988) 769-774. 

It is clear that a method that is only to be used 5 or 10 times requires much less vigorous testing than a method that is to be used as a quality assurance method over several years. The considerations for designing protocols for a ruggedness test are described for selecting both factors for testing and experimental designs in the relevant sections of this chapter. 

Some validation tests can provide valuable information that helps to design a more efficient ruggedness test. For instance, if the repeatability of the various stages in the method is already established then the order of an experimental design is not so critical and it is usually sufficient to perform duplicates for each experiment. These features will be discussed in more detail in the section on experimental designs. 

The first stage in deciding how to treat the results from a ruggedness test is to select a range of parameters to measure which will provide both qualitative and quantitative information on the method s performance. The second stage is to decide how best to evaluate the main effects, standard errors and interaction effects provided by the selected experimental design. For this discussion we will consider only the application of HPLC, normally one of the most complex analytical methods to evaluate. 

For each experimental design used for ruggedness results are calculated separately for each level tested. The usual results estimated by these designs are a main effect for each factor, interaction effects for all combinations of factors and a standard error that estimates the precision achieved throughout the study. 

The next operation is then to enter the data, namely the variable names and for each variable its nominal and extreme value. This is done by moving the pointer to the correct column and typing them in. As an example we shall input data for 7 variables from the literature (ref. 5). After typing the labels and 2 values for each variable (see Table 2.3) the LOTUS display should be as shown in Figure 2.6. One has not obtained the table of values to be used in the experimental design, which is the first step of the ruggedness procedure, but just the ordinary table of data. 

Ruggedness/robustness Defined based on an experimental design and data (sensitive parameters and a range for each parameter in the final test method)... 

Robustness Testing. Robustness testing studies the capacity of the method to remain unaffected by small, but deliberate variation in the method parameters. By means of a limited set of experiments (often using an experimental design approach), the critical parameters that may affect the ruggedness of the method can be identified, understood, and improvements made if necessary. 

W. Mulholland, P. L. Naish, D. R. Stout, and J. Waterhouse, Experimental design for the ruggedness testing of high performance liquid chromatography methodology, Chemom. Intell. Lab. Syst., 5, 263-270 (1989). 

Carlson R (1992) Design and optimization of organic synthesis. Elsevier, Amsterdam Box GEP (1952) Statistical design in the study of analytical methods. Analyst 77 879-889 Cochran WG, Cox GM (1957) Experimental designs. WUey, New York Small TS, Fell AF, Coleman MW, Berridge JC (1995) Central composite design forthe rapid optimisation of ruggedness and chiral separation of amlodipine in capillary electrophoresis. Chirahty 7 226-234... 

Carrying out the experiments described in the design. This is the experimental part of the ruggedness test ... 

The experimental order of this study was also changed from the ideal randomised and blocked design. This was justified for reasons of automation where column changes needed to be minimised. As for the aspirin study the validity of this compromise depends on the fact that the repeatability of the method, over a time span such as that required for the ruggedness test, had previously been established. 

The effect of each variable in the ruggedness test is determined by the difference between the average high and low levels, as is done in the Plackett-Burman design. However, the Youden technique, as modified by Steiner, differs from the Plackett-Burman technique in that the Youden-Steiner experiment is performed in duplicate, and the standard error is estimated differently. An estimate of the experimental error is calculated by equation 5. ... 

Ruggedness the capacity of an analytical method to remain unaffected and produce accurate data in spite of small but deliberately introduced changes in experimental conditions. Fractional factorial or Plackett Burman designs are frequently used to screen the impact of those changes. 

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