There could be many reasons, BP's original work showed RO varied from patient to patient. Receptor population, different level of affinity, etc. For every drug we prescribe we realize dose may need to be adjusted, BP meds for an example. Since we have an bioassay for LL RO; for example if 20% of patients in the study group had less than 50% RO and died, to me that is not drug failure, but treatment failure. When this molecule is used clinically I feel RO will be used to determine optimum dosing since there is no toxicity.