| Important to know if the drug is: |
| • Reaching required concentration in the effecting compartment. |
| • Affecting desired molecular target. |
| • Modulating the biochemical pathway. |
| • Achieving desired biological effect on the tumour cell. |
| • Achieving desired physiological effect on the tumour. |
| |
| There is a requirement for noninvasive assays, particularly when timing of peak biological activity is not known. |
| |
| Aim for hypothesis testing trials to: |
| • Support go/no go decisions: accelerate drug development or kill failures early. |
| • Establish dose and time response (scheduling). |
| • Examine drug combinations. |
| • Provide confidence to go forward to expensive large-scale trials. |
| |
| In this context, MR measurements are biomarkers, where, following the NIH Biomarkers Definitions Working Group (2001), a biomarker is a ‘characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention’ as distinct from a surrogate end point, which, when validated, is expected definitively to predict clinical benefit. Surrogate end points generally require evidence of validation for regulatory bodies. |
| Aim to operate the analysis at a level of computer software validation between publication standard quality assurance and ICH GCP (1996). |
| Have realistic guidelines (resource issues – who pays to develop methods and maintain facilities?). |
