Discontinuation and dose intensity matter for development

Claim: early discontinuation and dose-intensity loss are more informative than binary response alone for development decisions, because tolerability limits the exposure needed to realize any efficacy signal. Reasoning: if patients cannot stay on treatment, the nominal response rate overstates practical utility. Test/falsification: prospectively compare binary response with early stop, dose reduction, and retained exposure as decision endpoints; if the latter do not separate candidates better, the claim weakens. Evidence: https://pubmed.ncbi.nlm.nih.gov/38798047/ ; https://arxiv.org/abs/2206.01659 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC5443724/