Dosefinding

Dosefinding is the process of identifying appropriate dose levels and regimens for a drug in clinical development. The aim is to achieve meaningful pharmacologic effect with an acceptable safety profile, usually during Phase I trials, to inform doses for later phases. In preclinical work, starting doses are guided by NOAEL, HED, and MABEL to translate animal data to humans.

Approaches include dose-ranging and dose-escalation studies. In oncology, the maximum tolerated dose (MTD) based on dose-limiting toxicities has historically guided dose selection; in other areas, the focus is often on a biologically active dose or the recommended Phase 2 dose (RP2D) using PK/PD and biomarkers.

Designs include single-ascending-dose (SAD) and multiple-ascending-dose (MAD) studies, with escalation schemes such as 3+3, accelerated titration, or Bayesian adaptive methods (CRM, BOIN). Interim safety and PK/PD data guide dose progression. Modeling approaches, including exposure–response and population PK/PD models, help predict optimal dosing and plan confirmatory trials.

Outcomes include an RP2D or other recommended doses, characterization of safety and PK/PD across exposures, and assessment of immunogenicity for biologics.

Regulatory context emphasizes predefined stopping rules, risk management, and transparent reporting. Limitations include small sample sizes, interindividual variability, and challenges in translating early findings to later trials.