doseescalation

Dose escalation is a method used in pharmacology and clinical research to determine a drug's appropriate dose range by gradually increasing the dose in participants. The aim is to identify the maximum tolerated dose or the recommended dose for further testing, balancing potential efficacy with safety. In early-phase trials, dose escalation helps characterize pharmacokinetics and pharmacodynamics and guides dosing for later stages.

Phase I dose-escalation studies may use single-ascending-dose or multiple-ascending-dose designs, with schemes such as traditional 3+3, accelerated titration, or Bayesian model–based approaches. The design choice depends on the therapeutic area, existing data, and safety concerns. Dosing is guided by predefined rules and real-time safety data, and escalation may pause or stop if dose-limiting toxicities occur. In oncology, the goal is often the maximum tolerated dose, while in other fields the focus may be the biologically effective or recommended phase II dose.

Ethical and regulatory oversight is essential. Trials require informed consent, regulatory approvals, and monitoring by an independent safety committee. Doses are chosen to minimize risk while enabling meaningful pharmacokinetic and pharmacodynamic information.

Limitations include that findings in a small, early population may not generalize; adaptive designs and modeling aim to use data efficiently and may reduce exposure to subtherapeutic or harmful doses. Dose escalation remains a core element of early drug development, shaping subsequent trials and dosing recommendations.