Independent validation

PRESS for validation data. One of the best ways to determine how many factors to use in a PCR calibration is to generate a calibration for every possible rank (number of factors retained) and use each calibration to predict the concentrations for a set of independently measured, independent validation samples. We calculate the predicted residual error sum-of-squares, or PRESS, for each calibration according to equation [24], and choose the calibration that provides the best results. The number of factors used in that calibration is the optimal rank for that system. 

Cross-validation. We don t always have a sufficient set of independent validation samples with which to calculate PRESS. In such instances, we can use the original training set to simulate a validation set. This approach is called cross-validation. The most commom form of cross-validation is performed as follows ... 

When we examine the plots in Figure 56 we see that the PRESS decreases each time we add another factor to the basis space. When all of the factors are included, the PRESS drops all the way to zero. Thus, these fits cannot provide us with any information about the dimensionality of the data. The problem is that we are trying to use the same data for both the training and validation data. We lose the ability to assess the optimum rank for the basis space because we do not have independent validation samples that contain independent noise. So, the more factors we add, the better the calibration is able to model the particular noise in these samples. When we use all of the factors, we are able to model the noise completely. Thus, when we predict the concentrations for... 

Just as we did for PCR, we must determine the optimum number of PLS factors (rank) to use for this calibration. Since we have validation samples which were held in reserve, we can examine the Predicted Residual Error Sum of Squares (PRESS) for an independent validation set as a function of the number of PLS factors used for the prediction. Figure 54 contains plots of the PRESS values we get when we use the calibrations generated with training sets A1 and A2 to predict the concentrations in the validation set A3. We plot PRESS as a function of the rank (number of factors) used for the calibration. Using our system of nomenclature, the PRESS values obtained by using the calibrations from A1 to predict A3 are named PLSPRESS13. The PRESS values obtained by using the calibrations from A2 to predict the concentrations in A3... 

As is the case for PRESS, the variance of prediction can be calculated for predictions made on independent validation sets as well as predictions made on the data set which was used to generate the calibration. 

The increased speed of structure determination necessary for the structural genomics projects makes an independent validation of the structures (by comparison to expected properties) particularly important. Structure validation helps to correct obvious errors (e.g. in the covalent structure) and leads to a more standardised representation of structural data, e.g. by agreeing on a common atom name nomenclature. The knowledge of the structure quality is a prerequisite for further use of the structure, e.g. in molecular modelling or drug design. 

Zaragoza L, Hogan K. 1998. The integrated exposure uptake biokinetic model for lead in children independent validation and verification. Environ Health Perspect 106(6) 1551-1556. 

In a similar way, Voigt-Martin et al. [14] have solved the structure of [9,9 -bianthryl]-10-carbonitrile in three dimensions using 150 unique diffraction intensities, and independently verified the result with model building and image simulation techniques. As before, the potential maps are difficult to interpret, and independent validation is an important part of the structure solving procedure. 

To gain FDA approval or license for marketing, a pharmaceutical product must be shown to be safe and effective for its proposed or intended use. The drug company or sponsor must also provide evidence to show that the processes and control procedures used for synthesis, manufacture, and packaging are independently validated to ensure that the pharmaceutical product meets established standards of quality. The overall effort from the inception of a new molecular entity and the establishment of analytical, scale-up, and quality control procedures, to the collection of safety and efficacy data for consideration by the FDA as part of an NDA or BLA, is called the drug development process. 

While validating a production process, several steps were listed as they pertained to each of the components of manufacturing equipment, process conditions, personnel, and so forth. These key elements multiply rapidly when it comes to analytical methods validation. Take, for example, HPLC — the most commonly used method of analysis. A typical analytical method would involve use of columns, pumps, heaters, detectors, controllers, samplers, sensors, recorders, computers, reagents, standards, and operators — put together as a system. Each of these components and systems needs independent validation, followed by a validation of the system. Note that when this equipment is used to manufacture a product such a therapeutic proteins wherein HPLC techniques are used for the purification purpose, then all additional requirements of a manufacturing system also apply, including, but not limited to, the requirement that the equipment be of a sanitary kind. This limits the choice for manufacturers, and these considerations should be taken into account in the first selection of equipment. 

An outstanding example of how these law s are subject to modification was Einstein s elucidation of the mass-energy equivalence ( —me). Before that, the conservation of mass and the conservation of energy were considered to be independently valid. 

In general, HTE screenings generate leads together with a correlation between their properties and their structural and synthetic characteristics. Once leads and correlations of sufficient quality have been produced, a more detailed study at a conventional laboratory scale follows. Repeating the experiment in a conventional manner is an important check regarding the reproducibility of the HTE results on a larger-volume scale. Results should never be published without such a check, since the ability to independently validate a particular result should not be dependent on the HTE equipment used [20]. 

The correlations between the cellular readout(s) used and the pathway or phenotype that is being assessed must be independently validated. 

The American Heart Association (AHA) Guidelines 2005 state that Accurate measurement of blood pressure is essential to classify individuals, to ascertain blood pressure related-risk and to guide management. The auscultatory technique with a trained observer and mercury manometer continues to be the method of choice in the office. The oscillometric method can be used for office measurement, but only devices independently validated according to standard protocols should be used, and individual calibration is recommended (3). 

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