Human target validation classification
| HTV | Definition |
|---|---|
| High HTV | |
| Level 1 | Drug is on the market |
| 1.1 | Mortality/morbidity endpoint met in target population |
| 1.2 | Surrogate endpoint (approvable) met in target population |
| 1.3 | Confidence-generating endpoints met in target population |
| Level 2 | Clinical tool is hitting the target |
| 2.1 | Surrogate endpoint (approvable) met in target population |
| 2.2 | Confidence-generating endpoints met in target population |
| Level 3 | Drug is hitting a target in the pathway of interest |
| 3.1 | Mortality/morbidity endpoint met in target population |
| 3.2 | Surrogate endpoint (approvable) met in target population |
| 3.3 | Confidence-generating endpoints met in target population |
| Level 4 | Drug/clinical tool is hitting the target and/or pathway outside the target population |
| 4.1 | Surrogate endpoint (approvable) met |
| 4.2 | Confidence-generating endpoints met |
| Medium HTV | |
| Level 5 | Phenotypes/genotypes in the diseased state have been identified |
| 5.1 | Extreme (for example, naturally occurring mutants) |
| 5.2 | Heterogeneous (for example, based on population databases, patient cohorts) |
| Level 6 | Clinical challenge model |
| 6.1 | Nondrug; stress test of pathway (for example, fat meal, lipopolysaccharide [LPS] challenge) |
| Level 7 | Target affected in human ex vivo tissue manipulation |
| 7.1 | For example, platelet ADP stimulation, insulin secretion from human islets |
| Low HTV | |
| Level 8 | Target/target pathway is altered in healthy vs. diseased population |
| 8.1 | For example, positron emission tomography tracer data supportive, bioinformatics, in silico mapping |
| Level 9 | Target of interest is present in correct tissue/cell type |
| 9.1 | For example, bioinformatics, experimental evidence |
| Level 10 | No relevant human data |