| Unselected or all-comers | |
| Sequential testing strategy | The compound is first tested in the overall population and then in the marker-defined subpopulation or vice versa, according to the strength of preliminary data |
| Marker by treatment interaction | The marker is used as a stratification factor upfront: the overall study population is divided into two groups according to the marker status and each subpopulation is equally randomised to the experimental versus control arm |
| Marker-based strategy | Patients are randomly assigned to receive their treatment either based on the biomarker status or not; thus, determining a significant overlap of patients treated with the same regimen in both the biomarker-based and non-biomarker-based arm |
| Targeted or enrichment | All patients are screened for molecular alteration but only the subpopulation who either express a specific molecular alteration or not are enrolled in the clinical trial to assess the safety, tolerability and clinical benefit of a specific treatment |
| This design requires well-established assay reproducibility and accuracy and early evidence of benefit |
| Hybrid | Only the marker-defined subgroup is randomly assigned to have the treatment based on that marker, the others subgroups are assigned to the standard of care |
| It is similar to the enrichment design but also includes the non-marker-defined subgroup; thus, being the preferable choice when there is prior evidence of marker-based treatment |