EVALUATING CLINICAL UTILITY

To evaluate the clinical usefulness of a tumor marker, it is necessary to establish reference values, calculate predictive values, evaluate the distribution of marker values, and determine the role of the values in disease management. 

Reference values of a tumor marker are obtained from a healthy population, preferably with age- and sex-matched individuals. The determination of reference values is time-consuming and requires a large healthy population (n 120 subjects). Statistical analysis using the mean 2 standard deviation (SD) for a population with a gaussian (normal) distribution is a frequently used method. For a nongaussian distribution, the percentile method is a simple approach and often used (for further discussion of reference values, see Chapter 16). 

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Hayes, D. F., Bast, R Desch, C. E., et al. A tumor marker utility grading system (TMUGS) A framework to evaluate clinical utility of tumor markers. J. Natl. Cancer Inst. 818, 1456-1466... 

FDA device regulation is focused on the device and the device manufacturer. CLIA, on the other hand, focuses on laboratory quality, including the quality of the laboratory test results provided by the devices used, whether developed in-house or as a test kit in commercial distribution to multiple laboratories. The programs differ substantially in approaches and in data requirements. FDA requires unique submissions for each test under its purview, evaluates both performance and labeling, and requires demonstration of analytical validity and clinical validity as appropriate. CLIA inspects laboratories using a system approach based on key probes of the operating system. CLIA requires a demonstration of analytical performance and quality control but does not require a showing of either clinical validity or clinical utility. 

The PMA evaluation process, unlike the 510(k) process, is intended to establish intrinsic safety and effectiveness of a device, rather than comparability with a legally marketed predicate device. For PMA, the performance characteristics of a device must be established as a stand-alone application. In order for an IVD PMA to be approved, the sponsor must demonstrate that the device has clinical utility and that it is safe and effective for its intended use. Generally, the agency bases its determination of clinical utility on whether the device is recognized widely by health practioners or supported by peer-reviewed scientific literature as having reasonable clinical utility or usefulness. The PMA is the more stringent of... 

Three new positron emitting generator systems have been described. The practical availability of these radionuclides could significantly broaden the potential applications of positron emission tomography. The next few years should see human clinical trials undertaken to fully evaluate their utility for nuclear medicine. 

Potts JT, Jr., Bringhurst FR, Gardella TJ, et al. Parathyroid hormone Physiology, chemistry, biosynthesis, secretion, metabolism, and mode of action. In Degroot LJ (Ed.), Endocrinology. W.B. Saunders, Philadelphia, PA (1996) 920-965. Nussbaum SR, Zahradnik RJ, Lavigne JR, et al. Highly sensitive two-site immuno-radiometric assay of parathyrin and its clinical utility in evaluation patients with hypercalcemia. Clin. Chem. (1987) 33 1364-1367. 

As new imaging tools have become available, such as CT and MRI, many attempts have been made to evaluate imaging criteria for assessing the severity of acute pancreatitis. The first severity index of acute pancreatitis was developed in 1990 by Balthazar et al. (B2). The CT Scoring Index (CTSI) is a 10-point system based on the degree and the type of changes in pancreatic parenchyma and peripancreatic tissues as well as the extent of pancreatic necrosis. The majority of studies confirm its clinical utility for prediction of severity of AP (K6, LI, M20, S14, VI) however, some authors report CT to be ineffective (L13, L14). 

The clinical utility of this approach will depend on the results of these initial clinical trials evaluating l7(3-estradiol and the outcomes of current DESs in higher-risk patients, Speculations about the clinical results are that an improved healing and re-endothelialization, although not completely abolishing neointima formation, will allow a controlled... 

Other TP receptor antagonists have been developed (see 215-219 for examples), but their clinical utility remains to be evaluated. 

As with any medically driven scientific hypothesis, the ultimate value of the amyloid hypothesis is directly proportional to its clinical utility. A myriad of scientific achievements have occurred since George Glenner first identified the A/3 peptide in amyloidotic vessels in 1984 (150). Biochemical prowess combined with elegant genetics and careful neuropathological analyses have advanced the field to a point where there are numerous anti-amyloid molecules undergoing, or close to, therapeutic evaluation in AD patients. 

Nussbaum SR, Zahradrik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY. Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients witli hypercalcemia. Clin Chem 1987 33 1364-7. 

Stephan JJ. Clinical utility of bone markers in the evaluation and follow-up of osteoporotic patients why are the markers poorly accepted by clinicians. 

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