Step 1 — Considerations for preliminary identification of a potentially useful marker
- Is there a biological rationale for this marker? If so, the rationale can be used initially as part of the justification for the potential interest or value of the marker. If, however, a marker (or set of characteristics such as a cluster of expressed genes) is identified serendipitously or the biological rationale is not obvious, then preliminary data to support the suggestion that the marker may have some interest or be worth further investigation will be required. The data can include evidence that the marker predicts some outcome of interest; is associated with some clinical parameter; is prognostic or diagnostic; or appears to identify sub-populations of patients.
- Is there an assay system available that is working in at least one laboratory with reasonable reproducibility? Is there a reasonable scoring system?
- Has the marker been examined in normal as well as abnormal/diseased tissue? Has it been examined in different organ sites? This is not so much to establish exact distribution characteristics but to help determine the setting where the marker might have greatest value. The types of tissues that should be examined include benign diseases of the same organ and premalignant lesions. The source of so-called normal tissue should be described.
- Can a patient population be defined for which this marker may have utility? What is an expected range for the prevalence of this marker in populations of potential interest? Very rare (< 5%) or very prevalent (>95%) markers are likely to be useful in more circumscribed settings, e.g., they distinguish malignant from benign or definitively predict the response to therapy. Markers with intermediate prevalence may be useful to identify subsets of a patient population with different outcomes. The numbers of specimens that should be assessed at this stage will vary depending on the question being asked or the intended use of the marker. If prevalence is being assessed, then >20 specimens should be examined so that a marker present in 5% of cases would have a reasonable chance of being detected in the set of specimens. The numbers to be assessed for other questions will depend on the statistical design, the difference that would be meaningful to detect.
- Can the marker be measured in the types of specimens that will generally be available?