Dose-ranging studies (including discovery, preclinical and clinical)

Dose-ranging studies are critical experiments conducted in discovery, preclinical, and clinical settings to identify the most effective and safe dose for a particular drug candidate. These studies aim to determine the relationship between  dose and therapeutic response, toxicity, and side effects.

• In preclinical studies, dose-ranging experiments involve animal models to identify potential therapeutic windows and the doses that maximize efficacy while minimizing adverse effects. The starting doses and dosing regimen should be based on prior pharmacokinetic, pharmacodynamic, or in vitro studies. A range of doses should be tested until significant toxicity is observed. If severe toxicity occurs, researchers may test an intermediate dose to fine-tune the maximum tolerated dose. This helps ensure that the dose selected is both safe and effective for future studies. These studies help establish a safe starting dose for human clinical trials.

• In clinical trials, dose-ranging studies are typically part of Phase 1 and 2 trials. They aim to fine-tune the optimal dose based on human responses, often using different dose levels or dosing regimens (once daily vs. twice daily dosing) to balance efficacy with safety. Typically, a dose ranging study is tested in healthy human volunteers and will include normally 3 to 4 groups that receive different doses of the test drug. For example, a typical dose-ranging study may include: a low-dose group, medium-dose group and a high-dose group. The ideal outcome of a dose-ranging study is to bracket the desired clinical dose by showing that the next dose down has less efficacy and that the next dose above has no added efficacy and perhaps is associated with poor tolerability or high rates of adverse events. This data informs the choice of the dose for larger, more definitive Phase 3 trials.

Dose-ranging studies are integral to ensuring that the right dosage is selected for further clinical development, minimizing the risk of ineffective or harmful treatments reaching the market.