Blind Samples

Internal QC inclndes the nse of blanks, chemical calibrants, spiked samples, blind samples, replicate analysis, and QC samples. QC samples shotrld be homogeneous and stable. They shotrld be available in sufficient quantities. The use of control charts is recommended (see chapter 13). 

Fig. 111.12. (VII for temperature dependent lluorcsccnce LXAFS measurements of liquids wiih soli X-rays. The cell consists of holder ( ). window flange (2). double-sided flange (3) containing the liquid sample, blind flange (4). ihermoeouplc (5). cartridge healer (6), copper gaskets (8i. screw bolls )) and polymer corned beryllium window (10). During the experiment, the cell is mounted on (he cold huger (7) of a sample manipu Dior lOKj.

Other cases are known where ethics committee (IRB) approval has been forged (Blunt et al, 1998), patients have been put into several studies at once without the sponsors being aware of this, nurses have been required to recruit patients, disregarding the inclusion or exclusion criteria, investigators have sampled blinded material themselves attempting to unblind it and so on. 

B. Precision is demonstrated by the repeatability of analyses of replicate samples and replicate portions of the same sample. Accuracy is demonstrated by fortification recovery, calibration checks, blanks, and quality control samples (blind samples). 

Blind test data was classified 100% correctly between flawless and defect samples. Layer containing flaw was determined correctly in 97.2% of the cases (see Table 2 for details). 

Single-operator characteristics are determined by analyzing a sample whose concentration of analyte is known to the analyst. The second step in verifying a method is the blind analysis of standard samples where the analyte s concentration remains unknown to the analyst. The standard sample is analyzed several times, and the average concentration of the analyte is determined. This value should be within three, and preferably two standard deviations (as determined from the single-operator characteristics) of the analyte s known concentration. 

Agency. A second example of an external method of quality assessment is the voluntary participation of the laboratory in a collaborative test (Chapter 14) sponsored by a professional organization such as the Association of Official Analytical Chemists. Finally, individuals contracting with a laboratory can perform their own external quality assessment by submitting blind duplicate samples and blind standard samples to the laboratory for analysis. If the results for the quality assessment samples are unacceptable, then there is good reason to consider the results suspect for other samples provided by the laboratory. 

P IDs (piping and instrumentation diagrams) should identify instruments, sample locations, the presence of sample valves, nozzle blinding, and control points. Of particular importance are the bypasses and alternate feed locations. The isolation valves in these hues may leak and can distort the interpretation of the measurements. 

Sampling locations for the unit test should be readily and safely accessible. The sample gatherer should be able to easily access the sample point. An isolation valve should be installed at the location. If a blind is installed, this should be modified in advance of the test. The sample locations shown on the P IDs must be compared against the actual locations on the equipment. Experienced operators may provide insight into the suitability of the location in question. 

Temporary strainers and blinds installed Provisions for sampling... 

Unit checkout Check that required mechanical work has been completed, tags and blinds pulled, and temporary piping disconnected. Plant supervision must certify completion of work. Cancel all entry and work permits. Utility system has been commissioned. Check blind list and inspect lines close bleed, drain and sample valves. 

Figure 6.2. Sample symbols to overcome color blindness.

With the best observing conditions, it is possible for the trained observer to compete with photoelectric colorimeters for detection of small color differences in samples which can be observed simultaneously. However, the human observer cannot ordinarily make accurate color comparisons over a period of time if memory of sample color is involved. This factor and others, such as variability among observers and color blindness, make it important to control or eliminate the subjective factor in color grading. In this respect, objective methods, which make use of instruments such as spectrophotometers or carefully calibrated colorimeters with conditions of observation carefully standardized, provide the most reliable means of obtaining precise color measurements. 

In drug discovery, a chemist usually begins by investigating compounds that have already shown medicinal value. A fruitful path is to find a natural product, an organic compound found in nature, that has been shown to have healing characteristics. Nature is the best of all synthetic chemists, with billions of chemicals that fulfill as many different needs. The challenge is to find compounds that have curative powers. These substances are found in different ways random or blind collection of samples that are then tested, or collection of specific samples identified by native healers as medically effective. 

For a more realistic sample size than that in Example 7.7, one that contains 1.00 mol CO, corresponding to 6.02 x 1023 CO molecules, each of which could be oriented in either of two ways, there are 2602x10 (an astronomically large number) different microstates, and a chance of only 1 in 2< 02x l0" of drawing a given microstate in a blind selection. We can expect the entropy of the solid to be high and calculate that... 

A series of calibration standards (CS) is made up that covers the concentration range from just above the limit of detection to beyond the highest concentration that must be expected (extrapolation is not accepted). The standards are made up to resemble the real samples as closely as possible (solvent, key components that modify viscosity, osmolality, etc.). A series of blinded standards is made up (usually low, medium, high the analyst and whoever evaluates the raw data should not know the concentration). Aliquots are frozen in sufficient numbers so that whenever the method is again used (later in time, on a different instrument or by another operator, in another laboratory, etc.), there is a measure of control over whether the method works as intended or not. These so-called QC-standards (QCS) must contain appropriate concentrations of all components that are to be quantified (main component, e.g., drug, and any impurities or metabolites). 

Colors in a laboratory should be coordinated, just as in a home. If pre-finished work benches are to be installed, they might set the color scheme. While they are available in several colors or combination of colors, the choice is not unlimited. In one case, the laboratory operator was color blind, so his wife took over the job as decorator. First, she selected a two-color scheme for the work benches. Color chips in hand, she then chose a floor covering from a number of samples submitted. For the wall paint, she found a standard color of the recommended quality that harmonized with the cabinets. A few appropriate charts and a colorful cloth wall-hanging of pipes and valves completed the decor. The result received many favorable comments from visitors to the facility. 

Contact with the shoppers was restricted to field phase management study personnel, for two reasons. First, clearly defined lines of communication had to be maintained. Second, in order to ensure that the identity of the stores remained blind (i.e., unknown to everyone downstream from sample collection), in compliance with one of the design criteria, communication with the shoppers had to be restricted. Overall, limiting contact with shoppers to one entity and using modern technology, such as facsimiles and e-mail to facilitate and document communications between shoppers and the collection coordinator, were essential factors in the successful conduct of the sampling phase of the study. 

Establish detailed written protocols. A suitable test of the quality of the protocol is that a naive operator should be able to analyze accurately blind samples with no further instruction. 

Perform periodic unannounced audits of operator performance by submitting blind samples of known composition. Comparison of observed vs. expected results may reveal bias due to differences in methodology or flaws in technique. The results of the tests should not be made the basis of punishment or reward. 

A randomized, double-blind, placebo-controlled trial evaluating the use of a monophasic OC containing 30 meg ethinyl estradiol and 3 mg drospirenone, a progesterone with anti-androgenic effects, showed improvement in the treatment arm compared with placebo.31 In particular, appetite, food cravings, and acne improved. However, active treatment was not associated with a statistically significant improvement in the overall outcome measure, the Calendar of Premenstrual Experiences (COPE) scale, perhaps because of the small sample size (n = 82). 

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