You nailed it, the endpoint of treatment in this case is not a milligram dose or a serum value. Half life does not filter in, if RO drops and the drug is still present, I would try to increase serum levels till RO increases. This becomes the CLINICAL treatment, not the lap top treatment. Give flexibility to the clinician within a trial design and amazing results could be forthcoming. The endpoint is efficacy which can be measured simply by RO regardless of weight, gender lean body mass. And I am not peddling INCelldx kits, have whomever in Brazil do the study!!
Study design becomes touchy with adding a placebo blood draw and changing doses based on lab measurements, but can be done. I know if I were treating critical COVID in the ICU I would treat to max RO, and even go beyond the dose if needed since toxicity is not an issue.