Test series, design

Pleiss MA, Unger SH. The design of test series and the significance of QSAR relationships. In Ramsden CA, editor, Comprehensive medicinal chemistry. Vol. 4 Quantitative drug design. Oxford Pergamon Press, 1990. p. 561-87. 

E. G. Derouane, V. Parmon, F. Lemos and F. R. Ribeiro, Principles and methods for accelerated catalyst design and testing, Series 11 Mathematics, Physics and Chemistry, vol. 69, (Kluwer Academic Publishers, Dordrecht, 2002). 

As we have noted, eight tests (series A and C) represented a 23 factorial design involving type of interior finish, presence of a fiberglass insulation in the cavity, and load level (Table I). Series B was similar to A and C except for the absence of load and hardboard siding. In most cases, the four tests of series B could also be included in the analysis. 

As has been mentioned previously, mutual dissimilarily of the test compounds is a necessary but not sufficient criterion for a properly designed test series. In addition, the parameters which have been chosen to characterize the compounds must vary independently of oneanother. In order to fulfil both criteria an appropriate test series has to be designed so that the corresponding points are evenly distributed over the respective parameter space. 

After the number of test compounds which are to be selected from the basic set has been decided upon one can apply one of the series design techniques reported in the literature. Some of these methods apply to a restricted number of parameters (e.g. two in the Craig graphical method 12,13)) and structural variations (e.g. a limited number of aromatic and aliphatic substitution patterns as in the Topliss manual... 

Considering the last two paragraphs one encounters an other problem of systematic drug design In order to select appropriate test compounds one needs to know the relevant parameters. These in turn can only be found through structure-activity-analysis based on the selected compounds. In other words, one needs to know the results which are obtained from the test series before this series can be designed properly. How can this problem be solved As in other similar cases (e.g. the calculation of orbital energies in quantum mechanics) an iterative procedure can be applied. Such a procedure is visualized in Scheme 1. 

In conclusion, for series design and largely also for evaluation of test series by structure-activity-analysis, the parameters which are used to describe physicochemical properties should meet the following condition ... 

To prove their hypothesis, Bamford and Block (51) applied the diagnostic test previously designed by Gold and Jefferson (58) in their studies of hydrolysis of carboxylic anhydrides catalysed by tertiary bases. The technique employed involves the use of a series of tertiary bases having different relative abilities to assodate with Lewis acids and to act as Bronsted bases. Pyridine, a-picoline and 2,6-lutidine form... 

Thus, when a new expl compd is first prepd in the lab it is essential for max safety that a series of preliminary tests be conducted to determine its order of sensitivity (See Physical Tests for Determining Esplosives and Other Properties, Vol 1, pp VII-XXVI). These tests are designed to determine whether the compd can be handled at all, and if so, with what care it must be treated. It is important that much less than lg (ca 0.2g) of solvent- vet or dissolved new expl be prepd, because for some expls even lg is more than sufficient to kill an unprotected person. For this reason, the tests referred to above should be conducted in the order ... 

Initial Screening of Process Variables. A 2 X 5 factorial experiment was designed for the first test series, using a high and low extreme for each of five factors. Intermediate points of each factor were included to obtain a sense of direction. 

A unique feature of this volume is the large number of references to Lippincott s Illustrated Reviews Biochemistry, which is the biochemistry volume in the Lippincott series. Designated as InfoLink references, they are located at the end of each chapter. This permits a reader with an interest in learning additional information related to a particular topic to readily locate relevant material covered in the biochemistry review. InfoLink also emphasizes the interrelationships between these biomedical disciplines—a skill that is increasingly being tested by the USMLE, Step I. 

Descriptive studies do not formally test hypotheses rather, they generate hypotheses based on evaluation of research questions. As such, descriptive designs cannot assess causality. One common descriptive design that offers considerable information on selected outcomes, such as birth defects, is the case series design. As the name suggests, this design encompasses a series of cases with the same outcome. There is no comparison group. This type of study can raise... 

Hellberg, S., Sjostrom, M., Skagerberg, B., Wikstrom. C. and Wold, S. On the design of multipositionally varied test series for quantitative structure-activity relationships. Acta Pharm Jugosl., 1987, 37, 53-65. 

Upon completion of the design test series, a comprehensive report (or pubhca-tion) should contain precise data (cf Braun and Ohveros, 1997) concerning ... 

Well-designed QSRR studies are helpful in identifying these structural features within a family of analytes which affect retention in a given separation system. That, in turn, helps to explain the molecular mechanism of retention operating in the system. With a carefully designed test series of analytes the QSRR derived provide an objective, numerical comparison of individual separation systems. This is especially useful to quantitatively compare various stationary phase materials. 

The Reflotron system produced by Boehringer Mannheim (Fig. 31) has been specially designed for the small laboratory in medical practice. An essential demand when developing this system was easy performance of individual analyses or small test series of whole blood by personnel untrained in analytical work. Furthermore, results of an individual analysis should be available in just about 2-3 minutes. More than 50000 instruments of this series have been installed world-wide in laboratories and medical practice. 

---