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The traditional way of finding a dose looks only at severe side effects in the first month. Modern statistical designs can use all patients' data and count the grumbling, long-lasting problems that make people quit months later.
Phase 1 designs (BOIN, CRM, TITE variants) that incorporate late-onset toxicity, cumulative low-grade toxicity over multiple cycles, patient-reported tolerability and pharmacokinetics into dose selection, with a target of the 'optimal biological dose' rather than the MTD, and with backfill cohorts at lower doses. Regulators expect a model-based design; the 3+3 becomes the exception requiring justification.
Shares Wrong doses, Small-molecule kinase inhibitors, Immune checkpoint inhibitors.
Shares Wrong doses, Small-molecule kinase inhibitors, Immune checkpoint inhibitors.
Shares Wrong doses, Antibody-drug conjugate (ADC), Immune checkpoint inhibitors.