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Black ER, Falzon L, Aronson N. Gene Expression Profiling for Predicting Outcomes in Stage II Colon Cancer [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Dec. (Technical Briefs, No. 13.)

Cover of Gene Expression Profiling for Predicting Outcomes in Stage II Colon Cancer

Gene Expression Profiling for Predicting Outcomes in Stage II Colon Cancer [Internet].

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Definition of Terms

Biomarker

The Biomarkers Definitions Working Group defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.48

Gene expression profile (GEP or “signature”)

A GEP is one type of biomarker. According to Subramanian and Simon,49 a GEP is a biomarker in which the expression levels of multiple genes are combined in a defined manner to provide a score or a classifier. GEPs measure the activity or “expression” of multiple genes in a single RNA sample, which may reflect both normal and malignant cellular function. Various methods exist to measure gene expression, including the reverse transcriptase polymerase chain reaction and DNA microarrays. GEPs may have an important role to play in determining prognosis and guiding treatment decisions if found to be reliable, valid, and clinically useful.

Clinical validity

How consistently and accurately the test detects or predicts the intermediate or final outcomes of interest.50

For this Brief, data for clinical validity is defined as the relationship (e.g., sensitivity, specificity, accuracy, etc.) of the GEP results to the risk of disease recurrence and/or death after surgery for stage II colon cancer. Whether or not data are available about the incremental information provided by GEP testing when compared with standard clinical and pathological risk factors will be reported. Clinical validity is also defined as the relationship (e.g., sensitivity, specificity, accuracy, etc.) of the GEP results to the response to adjuvant chemotherapy currently used after surgery for stage II colon cancer. Again, the availability of data on the incremental information provided by GEP testing when compared with standard clinical and pathological risk factors will be noted.

Clinical utility

How likely use of the test is to significantly improve patient outcomes.50

Clinical utility is defined as the balance of benefits and harms when GEP testing is used to impact clinical decisionmaking, that is, the decision about using adjuvant chemotherapy. Clinical utility should reflect patient outcomes such as improved survival. As noted by Simon et al.,13 clinical utility requires that a test be actionable, that is, the medical indication for using the test is clear and the magnitude of outcomes or treatment effects associated with different test results are sufficiently great as to influence treatment decisions.

Analytic validity

How accurately and reliably the test measures the genotype of interest.50

The analytic validity of the GEP test is also important, and information about the extent of information on analytic validity will be assessed. Analytic validity relates to the reliability and validity of the test itself, that is, does it measure the genes that are part of the assay, and are the test results reproducible? Lack of reproducibility could result from both preanalytic factors (e.g., sample preparation) as well as analytic factors (such as reagents used.)

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