Clinical sensitivity

Data to establish the clinical validity of genetic tests (clinical sensitivity, specificity, and predictive value) must be collected under investigative protocols" (Holtzman and Watson, 1998, p. 28). 

Specifically, for genetic tests the sponsor should present evidence of sensitivity in terms not only of the ability of the test to detect specific mutation (analytic sensitivity), but also of the proportion of people with clinically significant disease that are detected by the test (e.g., who have the specific mutation detected by the test clinical sensitivity). 

Neuron-specific enolase (NSE). NSE is useful for monitoring the outcome of treatment and the course of disease in patients with neuroendocrine tumors, in particular small cell lung cancer and neuroblastoma. The test is not suitable as a screening or adjunct to diagnosis because of low clinical sensitivity and specificity. Elevated serum NSE concentrations are found in patients with ... 

There are proficiency testing programs that are geared toward clinical sensitivity or specificity by seeking to determine whether a disease can be detected versus other types of controls that are use to test sensitivity, selectivity, and most importantly, reproducibility and precision. With mass spectrometry, the controls are and should be no different than those used for other assays, with one interesting exception. Quality assurance materials prepared for MS/MS may not be useful in other assays that are less selective. The example is newborn screening where quality assurance/control QA/QC materials have a mixture of compounds present in the blood specimens. However, in less selective immunoassays, the mixture creates interferences. In addition, material is used to spike a blood sample is key and one should ensure there is no enzyme activity. We have encountered such a problem with a d/1 mixture of metabolites where one form was degraded in the prepared blood. 

Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer Assay of the complex improves clinical sensitivity for cancer. Cancer Res 1991 51 222-226. 

Diagnostic methods include SPT and quantification of specific IgE antibodies can be done using assays such as the ImmunoCAP or allergen-microarray. However, positive test results do not necessary confirm clinical sensitivity. Possible crossreactivity between tropomyosin from crustacean and mollusks with tropomyosin from insects and mites may have clinical significance and is discussed below. Sampson and Ho (1997) attempted to establish IgE values to predict clinical... 

CK-MB can be measured in numerous ways. Immunoassays developed in recent years have improved on the analytical and clinical sensitivity and specificity of the earlier immunoinhibition and immunoprecipitation assays. These assays now (1) measure CK-MB directly and provide mass measurements, (2) are easily automated, and (3) provide rapid results (<30 minutes). Mass assays reliably measure low CK-MB concentrations in both samples with low total enzyme activity (<100 U/L) and with high total enzyme activity (>10,000 U/L). Furthermore, no interferences from other proteins have been documented. The majority of commercially available immunoassays that use monoclonal anti-CK-MB antibodies are the same as those listed in Table 5-2 for cardiac troponin assays. Excellent concordance has been shown between mass concentration and activity assays. A primary reference material is commercially available to assist in harmonization. If used for assay standardization, then this material allows... 

The probability of classifying a result as positive (exceeding the cutoff), in case the true value indeed exceeds the cutoff, is called the clinical sensitivity. Classifying a result as negative (below the cutoff), in case the true value indeed is below... 

One approach for determining the recorded performance of a test in terms of clinical sensitivity and specificity is to determine the true concentration of analyte using an inde-... 

LPS measurement on serum is used to diagnose acute pancreatitis. The clinical sensitivity is 80% to 100% depending upon the selected diagnostic cutoff. The clinical specificity is 80% to 100% depending upon the mix of patient population studied. After an attack of acute pancreatitis, serum LPS activity increases within 4 to 8 hours, peaks at about 24 hours, and decreases within 8 to 14 days. Concentrations often remain elevated longer than those of AMY do. Elevations between 2 and 50 times the upper reference limit have been reported. The increase in serum LPS activity is not necessarily proportional to the severity of the attack. ... 

The predictive value model includes the clinical sensitivity, specificity, and predictive value of a test. By varying the decision level, clinical sensitivity and specificity will change in opposite directions. An optimal decision level can be selected based on the strategies outlined in Chapter 15. 

The detection of telomerase activity or hTERT mRNA in excretion, secretion, brushings, and washings has been evaluated. In pancreatic, secretion samples, which contain freshly exfoliated cells, detection of telomerase activity was encouraging for cancer detection. Telomerase activity was also found to be useful in distinguishing between adenoma and carcinoma in intraductal papillary-mucinous tumors, which can sometimes be difficult to diagnose. In bronchial brushing samples, the clinical sensitivity of cancer detection is below 70% and false-positive results are commonly encountered because of contamination witli lymphocytes, which contain measurable telomerase activity. The measurement of telomerase is also expected to become a useful... 

Additional markers of catecholamine overproduction have been employed to improve the biochemical detection of neuroblastomas. Free dopamine may be abnormal in urine from neuroblastoma patients with VMA and HVA excretion. Combined testing for VMA, HVA, and dopamine may therefore improve tumor detection, and in 1993 an international consensus report on neuroblastoma diagnosis added dopamine to the Hst of acceptable measurements to document the adrenergic nature of the tumor. Plasma measurements of dopamine and L-dopa, the amino acid precursor of dopamine, may also have clinical value and allow the alternate use of plasma. Measurement of methylated metabolites, especially normetanephrine, has also been explored. When urinary normetanephrine, metanephrine, methoxytyra-mine, dopamine, norepinephrine, VMA, and HVA were measured, clinical sensitivity for detection of neuroblastomas was 97% to 100% when results of normetanephrine testing were coupled either with VMA in the infants or with HVA in children greater than age 1. Even with an extended panel of catecholamines and metabolite measurements, a low incidence of nonsecreting tumors continues to be identified and should be considered in the interpretation of a negative test result. 

Hb H detection by this method is laborious to perform and is quite subjective. However, for the detection of the two a-gene cis deletion (-/aa) of a -thalassemia, the test is reported to have a clinical sensitivity of 0.47 and a specificity of 0.99. ... 

Clinical sensitivity, chnical specificity, positive predictive value, negative predictive value. ... 

Numerous clinical studies involving cTnl and cTnT have been published pertaining to AML Several have demonstrated that the clinical sensitivity of cardiac troponin is similar to that of CK-MB during the first 48 hours after the onset of chest As an early marker for AMI,... 

Figure 44-23 Clinical sensitivities (with 95% confidence limits) of creatine kinase-2 (CK-MB), myoglobin, and troponins I and T (cTr-l, cTr-T) for AM as a function of time from presentation at the emergency department (ED). (Data from Tucker JF, Collins RA, Anderson Aj, Houser j, Kalas j, Apple FS. Early diagnostic efficiency of cardiac troponin I and cardiac troponin T for acute myocardial infarction. Acad Emerg Med 1997 4 13-21.)...

LD isoenzymes and total LD activity are no longer measured in clinical practice. For historical perspective, for patients having an AMI, serum total LD values become elevated at 12 to 18 hours after the onset of symptoms, peak at 48 to 72 hours, and return to below the upper reference limit after 6 to 10 days. LD-1 rises within 10 to 12 hours, peaks at 72 to 144 hours, and returns to normal in approximately 10 days after AMI, paralleling total LD. The elevation patterns of LD-1 and total LD contrast with the elevation patterns of total CK and CK-2, which peak at 24 hours and return to below the upper reference Limit within 72 hours after the onset of AML Because of its prolonged half-life, LD-1 is a clinically sensitive (90%) marker for infarction when used more than 24 hours after occurrence. The LD-1 increase over LD-2 in serum after AMI (the so-called flipped pattern, in which the LD-l/LD-2 ratio becomes >1.0) has a clinical sensitivity of about 75% in patients suspected of having sustained an AMI. ... 

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