Dose Escalation Study
A clinical trial testing successively higher doses in small groups to determine the maximum tolerated dose. Single ascending dose (SAD) and multiple ascending dose (MAD) designs are standard Phase I approaches. Semaglutide's clinical dose titration schedule reflects dose escalation principles.
Technical Context
The traditional 3+3 design: 3 patients at each dose level; if 0/3 DLTs → escalate; if 1/3 DLTs → add 3 more patients (if 1/6 DLTs → escalate, if ≥2/6 → MTD exceeded, previous dose = MTD); if ≥2/3 DLTs → MTD exceeded. Limitations: treats MTD as a fixed threshold, uses limited data at each level, tends to recommend doses below the true MTD. Model-based designs (continual reassessment method, CRM; Bayesian optimal interval, BOIN) use accumulating data to continuously update the dose-toxicity relationship and target a specific DLT rate (usually 20-30%). Accelerated titration designs (single patient per cohort until first toxicity) can speed initial escalation through clearly sub-therapeutic doses. Peptide-specific considerations: immunogenicity may be dose-dependent and delayed, requiring extended observation windows.