Tumor markers clinical applications

The premarket notification application, 510(k), is reviewed by the FDA scientific staff. This evaluation takes into consideration tumor-associated analytes, test requirements, medical usefulness of the test system for a particular clinical claim, and its application (i.e., monitoring or treatment follow-up). The FDA determines the appropriate performance requirements for each tumor analyte category. The agency s staff considers factors, such as consequences of a false positive or false negative, and the importance or impact of an absolute versus a significant change in the results or values of the tumor marker tests. The performance criteria (parameters) of a particular tumor marker test are compared with those of previously... 

The establishment of performance criteria for a given tumor marker test is not a simple process because accuracy and precision are unique for each type of analyte and its application. Establishing methodological limits for accuracy, precision, sensitivity, and specificity often requires standard reference materials, quality control materials, comparative studies, and actual clinical specimens. Accuracy and precision must be measured over the analyte reportable range for which the device is intended to be used. Sensitivity and specificity must be considered with respect to the intended clinical use of the device. Also, the indications for use should be carefully considered in the design of the study protocol. The indications for class II should be to monitor residual tumor after surgery (or radiation), the recurrence of tumor, or response to therapy. A 510(k) must provide clear evidence that the device is accurate, safe, effective, and substantially equivalent to a device legally marketed in the United States. 

It is the goal of array-based prognostics to utilize a panel of markers that are more accurately able to stratify patients into prognostic groupings. There are several examples in the literature of biomarker panels identified by microarray analysis that may have some relation to prognostic outcome (4, 77, 78, 79,80). However, the issue remains that many of these biomarker panels do not afford sufficient specificity or sensitivity to warrant clinical application. Microarrays offer the potential to profile tumors at a finer level of detail than what can be obtained by the pathologist however, it is the reliance on classification from traditional pathology that has confounded many studies. 

Bates SE, Clinical application of serum tumor markers, Ann. Intern. Med., 115 623-638, 1991. 

Modified from Diamandis EP. Tumor markers Past, present, and future. In Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK. Tumor markers Physiology, pathobiology, technology, and clinical application. Washington DC AACC Press, 2002 5. 

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