doseranging

Doseranging is a methodological approach in pharmacology and related fields that involves testing several dosage levels of a substance to map the dose–response relationship and identify an optimal dose that balances efficacy and safety. It is commonly used in early-stage drug development, but can also apply to veterinary medicine, agriculture, and toxicology assessments.

In practice, dose-ranging studies may be conducted as phase I or phase II trials, using escalating-dose or stepwise cohorts. Randomization and, when possible, blinding are used to reduce bias. Typical endpoints include pharmacodynamic or surrogate efficacy measures, as well as adverse events and tolerability. Pharmacokinetic/pharmacodynamic modeling and exposure–response analyses are often employed to characterize the relationship and to estimate parameters such as ED50, EC50, NOAEL, and maximum tolerated dose (MTD).

Outcomes serve to select a dose or a small range for confirmatory pivotal trials and to establish a recommended dose. Adaptive dose-ranging designs, including Bayesian dose finding and escalation with overdose control, may allow more efficient identification of the therapeutic window while minimizing subject exposure to subtherapeutic or unsafe doses.

Limitations include ethical considerations, small sample sizes, and disease heterogeneity that can obscure true dose-response relationships. External validity depends on population similarity; results may not transfer across indications, populations, or comedications. Regulatory agencies often expect robust dose-ranging data to support dose selection in later-stage trials and labeling.