Experimental Study Design

This book, which focuses on biological considerations in clinical trials, is written very much in this spirit. While study design, experimental methodology, and statistical analysis are central characters in our discussions of new drug development, their importance lies in their role in the development of drugs that influence a patient s biology for the better. 

There are two fundamental types of study design experimental and nonexperimental (Piantadosi, 2005). Piantadosi defines an experiment as a series of observations made under conditions in which the influences of interest are controlled by the research scientist. This book deals largely with experimental studies. In nonexperimental studies, the research scientist collects observations but does not exert control over the influences of interest. Nonexperimental studies are often called observational studies, but this term is inaccurate it does not definitively distinguish between nonexperimental studies and experimental studies, in which observations are also made. Some nonexperimental study designs are discussed in Chapter 13. 

There are two components to evidence-based medicine and two related sets of responsibilities. The first component is clinical research. Clinical research is a scientific endeavor that provides evidence concerning potential therapeutic interventions. This book has focused on one particular therapeutic intervention, drug therapy. Once clinical trials have been conducted, the evidence obtained is published in clinical communications in journals. Everyone involved in clinical research has the responsibility to provide the best possible evidence in this manner. As noted throughout the book, this includes all aspects of clinical research study design, experimental methodology and clinical operations, analysis and interpretation, and also accurate and complete representation of study findings in clinical communications as discussed in Section 13.6. 

If forced to summarize the purposes of study design, experimental methodology, and statistical analysis in one sentence each, the following might be suitable ... 

Therefore, an appreciation of study design, experimental methodology, statistical analysis, and clinical interpretation is vital for clinicians who must decide whether the evidence presented in journal publications is adequate and reliable and therefore constitutes an appropriate basis for clinical care. 

In the last part of Chapter 7.4 (Transient Studies) the experimental work on ethylene oxidation was shown. There the interest was to investigate what occurs and how fast, after a thermal runaway started. The previous chapter discussed the criteria of how to design reactors for steady-state operation so that runaways can be avoided. One more subject that needs discussion is what transient changes can cause thermal runaways. 

In reporting the results of such studies, the experimental design should be carefully described so readers are able to assess the precise significance of the reported values. 

Empirical kinetics are useful if they allow us to develop chemical models of interfacial reactions from which we can design experimental conditions of synthesis to obtain thick films of conducting polymers having properties tailored for specific applications. Even when those properties are electrochemical, the coated electrode has to be extracted from the solution of synthesis, rinsed, and then immersed in a new solution in which the electrochemical properties are studied. So only the polymer attached to the electrode after it is rinsed is useful for applications. Only this polymer has to be considered as the final product of the electrochemical reaction of synthesis from the point of view of polymeric applications. 

This approach demonstrates that use of only a part of this procedure will represent a step forward over the trial-and-error method of formula and process modification. It is not always necessary to carry these studies to completion. For example, once the designed experimentation has been completed, one might be able to accomplish the task simply by analyzing the graphs therefore, further mathematical treatment or search programs will not be necessary. Some of the examples in the following section illustrate this fact. 

Designed experimentation, involving mostly some type or modification of factorial design, has been used to study many different types of formulation problems. These include a pharmaceutical suspension [21], a controlled-release tablet formulation [22], and a tabletcoating operation [23]. In the latter case, Dincer and Ozdurmus studied an enteric film coating and utilized the steepest descent graphic method to select the optimum. 

Category IA Strongly recommended and supported by well-designed experimental, clinical, or epidemiologic studies. 

In conclusion, phytic acid forms soluble complexes with Ca2+ at intestinal pH under a variety of conditions and fails to inhibit Ca2 bioavailability to mice in our experimental system. Despite the hazard in direct extrapolation of results obtained with animals kept on a well-defined dietary regimen to humans consuming a complex diet, many elements of which affect Ca2+ bioavailability, our data demonstrate the need for a reevaluation of the putative antinutritional properties of dietary phytate. Our further contention that adequate levels of dietary phytate may actually be beneficial due to its food preserving properties and its protection against colonic cancer will warrant a prospective epidemiological human study designed to assess the longterm effects of dietary phytate on mineral bioavailability and inflammatory bowel diseases. 

The first precise or calculable aspect of experimental design encountered is determining sufficient test and control group sizes to allow one to have an adequate level of confidence in the results of a study (that is, in the ability of the study design with the statistical tests used to detect a true difference, or effect, when it is present). The statistical test contributes a level of power to such a detection. Remember that the power of a statistical test is the probability that a test results in rejection of a hypothesis, H0 say, when some other hypothesis, H, say, is valid. This is termed the power of the test with respect to the (alternative) hypothesis H. ... 

Subsequent kinetic studies designed to elucidate the experimental rate law were conducted on o-xylene solution. Individual runs in general displayed outstanding linearity (Figure 2). The short induction... 

To implement the principles of the basic system and extended basic systems into experimental systems operated in several operational modes. The analytical models developed in this study will be used to design experimental operational conditions and to investigate the results obtained. 

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