The Premarket Evaluation Process

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. 

The FDA evaluates each tumor marker test against its own labeling claims as to how well it performs and compares it with other cleared and marketed devices identified in the 510(k) submission. The intended use claim for monitoring must be supported by valid scientific and clinical data. Labeling a tumor marker test for a particular claim can mean that the testing system may have to show supporting data for that claim. For example, a tumor marker proposed for a monitoring claim will require laboratory and clinical data to support that claim (4,5). 

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