The Use of Positive Control

Clearly, there are many antithrombotic agents that can be used to compare and contrast the antithrombotic efficacy and safety of novel agents. The classic antithrombotic agents are heparin, warfarin, and aspirin. However, new, more selective agents such as hirudin, low molecular weight heparins, and clopi-dogrel are commercially available that will either replace or augment these older treatments. Novel 

The early in vivo evaluation of compounds that demonstrate acceptable in vitro potency and selectivity requires evaluation of each compound alone in order to demonstrate antithrombotic efficacy. The antithrombotic landscape is becoming complicated by so many agents from which to choose that it will become increasingly difficult to design preclinical experiments that mimic the clinical setting in which poly-antithrombotic therapy is required for optimal efficacy and safety. Consequently, secondary and tertiary preclinical experiments will need to be carefully designed in order to answer these specific, important questions. 

Schumacher WA, Heran CL, Steinbacher TE (1996a) Low-molecular-weight heparin (Fragmin) and thrombin active-site inhibitor (argatroban) compared in experimental arterial and venous thrombosis and bleeding time. J Card Pharmacol 28 19-25 

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The use of positive controls is optional, but the FDA has nevertheless developed a list of preferred and acceptable inhibitors for use in reaction phenotyping studies that can be applied to CYP inhibition... 

Since the identification tests are carried out without the use of positive controls or standards, they owe their robustness and reliability to the selectivity of the chemical reaction and the recognizability of the color produced. Especially the selectivity of the chemical reaction will naturally depend entirely on the actual reaction in question, but a few general remarks should be made. 

In Fig. 15-9 two potentiostatically controlled protection rectifiers and an additional diode are included to drain peak currents. At pipeline crossings with an external rail network (e.g., in regions outside the urban area), the forced stray current drainage should be installed as close as possible to the rails that display negative potentials for the longest operation time. The currents absorbed from the positive rails continue to flow also in the region outside the rail crossings. Here the use of potentiostatically controlled rectifiers is recommended these should be connected not only to the rails but also to impressed current anodes. 

Positive Controls. Where possible, positive controls should be chosen that are structurally related to the test article. This increases confidence in the results. In the absence of structurally related mutagens, the set of positive controls given in Table 6.7 can be used. The use of such controls validates each test run and helps to confirm the nature of each strain. Pagano and Zeiger (1985) have shown that it is possible to store stock solutions of most routinely used positive controls (sodium azide, 2-aminoanthracene, benzo[u]phyene, 4-nitroquinoline oxide) at — 20°C to — 80°C for several months, without loss of activity. This measure can help reduce potential exposure of laboratory personnel. 

To clarify farther the WMA position on the use of placebo-controlled trials, the WMA Council issued, during October 2001, a note of clarification on Paragraph 29 readable at the end of this list. 

Control Rod Drive System. Positive cure reactivity cuulrol is maintained by the use of movable control rods interspersed throughout the core. 

The Use of Positively Charged or Low Surface Free Energy Coatings versus Polymer Brushes in Controlling Biofilm Formation... 

Instrumentation and control. Operation of a fluid cracking unit is simplified by the use of automatic controls. As a further aid, graphic panel-boards are sometimes employed which utilize small indicating instruments located at the appropriate positions in a simplified flow diagram of the process (68,309). Audible and visual alarms, as well as automatic controls for emergency shutdown of the unit, are often provided (202). 

A compound is concluded to be an inducer if reproducible, statistically significant, and dose-dependent induction effects are observed. The FDA recommends the use of the criterion of "40% of higher of the activity of positive controls" as a positive response (www.fda.gov/cber/gdlns/interactstud.htm). 

Validation of the result is essential and is achieved through the use of positive and negative controls to assess the method (e.g., labeling with an alternative antibody, using a known positive system as positive controls and determining nonspecific binding as a negative control). 

To check for inhibitors, an internal control can be added to the sample. Alternatively, two portions of the specimen can be tested, with one of them containing an added target. For a specimen to be considered negative, the test result for the specimen amplified directly must be negative and the specimen with added nucleic acid must be positive. The amount of target nucleic acid added to the patient specimen should be close to the limit of detection of the assay, so that low levels of inhibition can be detected. The use of these controls is often discontinued if the inhibition rate is determined to be less than 1%. 

Gaitonde, N.Y. J.M. Douglas. 1969. The use of positive feedback control systems to improve reactor performance. AIChE J. 15 902-10. 

Quality control (QC) refers to the operational techniques and activities that are used to fulfill requirements for quality. Internal quality control comprises the routine practical procedures that enable the analytical chemist to make a decision on whether to accept a result or a group of results as fit for purpose, or reject them and repeat the analysis. Tools for quality control include the use of reference standards and certified reference materials, the use of positive (spiked or incurred) and negative control samples and control charts, replicate analyses, and proficiency tests. Quality control in the laboratory is discussed in more detail in Section 10.5 of this chapter. 

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