Table 2
Comparison of 3 study designs to evaluate clinical utility of biomarkers
| Study design | A. Biomarker enrichment | B. Biomarker stratified or by treatment interaction | C. Biomarker strategy |
|---|---|---|---|
| Schematic diagram |  | ||
| Primary question | Is new treatment in biomarker-positive patients superior to standard of care? | Is improvement observed with the new treatment in biomarker-positive patients significantly better than that in the biomarker-negative patients? | Is a management strategy based on biomarker testing with consequent treatment modification in biomarker-positive patients superior to standard of care? |
| Inception cohort | Biomarker-positive subpopulation | All comers | All comers |
| Stratification | No | By biomarker status | No |
| Randomization | By treatment | By treatment | By biomarker testing |
| Information obtained | Informs on whether new treatment in biomarker-positive patient is clinically useful. | Informs on whether biomarker status is a determinant of response to treatment options, and whether such testing would be clinically useful. | Informs on whether biomarker testing and treatment modification based on such testing is clinically useful. |
| Study design | A. Biomarker enrichment | B. Biomarker stratified or by treatment interaction | C. Biomarker strategy |
|---|---|---|---|
| Schematic diagram | | ||
| Primary question | Is new treatment in biomarker-positive patients superior to standard of care? | Is improvement observed with the new treatment in biomarker-positive patients significantly better than that in the biomarker-negative patients? | Is a management strategy based on biomarker testing with consequent treatment modification in biomarker-positive patients superior to standard of care? |
| Inception cohort | Biomarker-positive subpopulation | All comers | All comers |
| Stratification | No | By biomarker status | No |
| Randomization | By treatment | By treatment | By biomarker testing |
| Information obtained | Informs on whether new treatment in biomarker-positive patient is clinically useful. | Informs on whether biomarker status is a determinant of response to treatment options, and whether such testing would be clinically useful. | Informs on whether biomarker testing and treatment modification based on such testing is clinically useful. |