Specificity of the tests

To accomplish this, you need to specify either in the quality plan or the documented procedures, the inspections and tests you intend to carry out to verify that the product meets specified requirements. In Part 2 Chapter 4 there is a description of a Design Verification Plan and this includes a specification of the tests and inspections to be performed on each production item as a means of ensuring that the qualified design standard is being maintained. This requires that you produce something like an Acceptance Test Plan which contains, as appropriate, some or all of the following ... 

Red blood cells also contain sufficient acid phenylphospha-tase for mild hemolysis to cause false elevations. Therefore, inhibitors such as ethanol, formaldehyde, copper sulfate> and 1-tartrate have been used to inhibit selectively the enzyme of one or more tissues and enhance the specificity of the test (101). Ethanol is unsuitable because it inhibits the enzyme from erythrocytes and prostate simultaneously, and because it yields serum activities which correlate poorly with prostatic disease. Formaldehyde inhibits the erythrocytic enzyme and has been said to yield clinically satisfactory results. The copoper resistant acid phosphatase of serum is elevated by metastatic carcinoma of the breast, as well as by other metastatic cancers, and is also elevated by a wide variety of non-cancerous diseases. 

A program employing a immunochemical stain based test to screen tissues for a specific effect will be discussed as an example. This test uses small amounts of antibody tissues for a specific effect, and the presence of an immunologically bound stain is considered a positive result. If the sensitivity and specificity of the test and the prevalence of biochemical effect are known, Bayes theorem can be used to predict what proportion of the tissues with positive test results will have true-positive results (actually be effected). 

Sensitivity of immunological stain = 96% = 0.96 False-negative error rate of the test = 4% = 0.04 Specificity of the test = 94% = 0.94 False-positive error rate of the test = 6% = 0.06 Prevalence of effect in the tissues = 1% = 0.01... 

Suppose a pathologist is uncertain about an animal s cause of death and obtains a positive test result for a certain pathology. Even if the pathologist knows the sensitivity and specificity of the test, that does not solve the problem, because to calculate the positive predictive value, it is necessary to know the prevalence of the particular tissue or effect that the test is designed to detect. The prevalence is thought of as the expected prevalence in the population from which the animal comes. The actual prevalence is usually not known, but often a reasonable estimate can be made. 

Another issue of relevant importance to the interpretation of analytical results is the analytical specificity of the test, particularly when in an immunobased assay. Specificity is exquisite in immunochemical assays but, at the same time, it can be exquisitely troublesome. For example, when an immunochemical assay for the penicilloyl group is used to monitor the pharmacokinetics of penicillin elimination from the serum of treated animals, the measured levels remain high for at least several weeks, although the antibacterial activity was all eliminated from bovine serum within 24 h after injection. This is because the immunochemical assay measured not only the free drug but also the penicilloyl groups covalently bound to proteins in serum. The half-life of these bound residues is roughly equal to the half-life of the proteins in the circulation. 

Durometer. The Durometer hardness test was developed for and is used for determining the hardness of elastomers. The Durometer is a hand-held, spring-loaded instrument which when pressed against the sample forces a conical steel indenter into the surface. Durometer hardness numbers range from 0 to 100 and are read directly from the attached dial indicator. Several load scales are available, but the A scale (8 N = 822 gf) and the D scale (44.5 N = 4.54 kgf) are most common. Specifics of the test procedure are discussed in ASTM D2240 (2). Lighter load scales and larger diameter indenters are available for very soft materials such as foam. 

ISO 37 refers to ISO 584373 for specification of the test machine. This standard was produced to avoid the need to attempt description of a complex engineering instrument in a testing standard. It is intended that all test methods using a tensile machine will refer to this document, which specifies requirements quite comprehensively, including tolerances on the measurement of force and extension. 

Lethal dose LD50 gives the concentration that caused 50% of fatalities within 5 days in an animal population exposed once to the concentration. It may be an oral or dermal exposure and is expressed in rrigkg 1 of organism with a specification of the test animal used. 

Specification of the Testing Requirements and Acceptance Criteria, and Implementation of Change after Authorization... 

An inappropriate coating procedure for dsDNA may reduce the specificity of the test. Only ssDNA binds to the hydrophobic surfaces coated with polystyrol, the coating material generally used in ELISAs (E8). Cationic carriers for dsDNA binding, such as poly-L-lysine and protamine sulfate, may result in false-positive antibody reactions (B24). Another binder, an amphipolar ion-pair reagent, has been shown to be fully inert to immunoglobulins. 

Lymphocyte stimulation test shows that the lymphocytes from patients with food allergy are more often stimulated by the food antigen than the lymphocytes of control subjects, although both sensitivity and specificity of the test have been low in most patients. 

One of the problems with the diagnosis and treatment of EPM is that the sensitivity and specificity of the tests available currently to diagnose this disease continue to be debated and antibodies to S. neurona may persist in the cerebrospinal fluid (CSF), making it difficult to evaluate treatment efficacy. A negative result on Western blot of a CSF sample is evidence of absence of infection (Daft et al 2002). It also indicates resolution of infection and is the most reliable predictor that a horse will not relapse if the treatment is discontinued. 

The certificate should include tests on identification of the active ingredient, cissay of the active ingredient (or equivcilent tests) and other relevcint tests. If the specifications of the tests are not stated in the certificate itself, the finished product specifications should be enclosed together with the analytical certificate. 

Acetest and Ketostix are also suitable for detecting ketone bodies in urine. The sensitivity and specificity of the tests are the same as outlined for serum. 

Reporting results for qualitative assays in infectious disease is simple The nucleic acid is either present or not detected in the patient specimen. Further relevant information that is useful when reporting results includes the detection limit and specificity of the test and the rate of inhibition for a given specimen type, particularly for assays that do not contain an inhibition control. 

The specificity of the test was significantly improved by abandoning the nonspecific colorimetric procedures in favor of high-performance liquid chromatography (HPLC)." NBT-PABA has advantages over the pancreolauryl test in that the patient procedure can be completed in a single day but the synthetic peptide is not now easily available, and the test has a lower diagnostic sensitivity and specificity for pancreatic insufficiency than does fecal elastase (see Table 48-8). 

When a similar fat load, was used without the inclusion of protein and carbohydrates, peak C02 occurred later in some patients. In 53 patients in whom CO2 excretion peaked within 6 hours, the sensitivity and specificity of the tests were 100% and 96%, respectively. Breath samples for C02 measurement are not easily transportable, and the requirement for a scintillation counter and the administrative regulations surrounding the use of radioisotopes deter many laboratories from using the test. 

Timely preformulation data availability is critical because it is an essential prerequisite of development. Delayed progress may result if preformulation data are not available on time. For example, before drug release for safety evaluation, the specifications of the test article must be established. Physical properties, such as melting point, ultraviolet spectrum, and thin-layer... 

Note that P(D+) is often called the prevalence of the disease in a population. Its complement is P(,D-) = 1 - P(P>+). Prevalence of a disease is estimated through the use of epidemiologic studies and not clinical trials. Thus, to fully evaluate the utility of the new diagnostic test, we must have an estimate of the prevalence of the disease, the sensitivity of the test, and the specificity of the test. 

Show that the true negative rate of a diagnostic test is a function of the sensitivity and specificity of the test and the prevalence of the disease. 

C. trachomatis, and false-positive results are reported with other Chlamydia species, as well as with some gram-negative bacteria. The sensitivity and specificity of the test are generally lower when urine specimens are used. " " ... 

The specifications of the test procedures should be divided into the following sections ... 

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