What is meant by preclinical, Phase I, Phase II, and Phase III clinical evidence?
Preclinical and clinical phases (Phase I, II, and III) represent sequential stages of drug development that evaluate the safety and efficacy of active compounds before and during human use:
1. Preclinical evidence: Based on laboratory (in vitro cellular assays) and animal study (in vivo models) results. Its objective is to elucidate the mechanism of action, demonstrate biological plausibility, and characterize pharmacokinetic profiles and early toxicity profiles prior to initiating human administration.
2. Phase I clinical evidence: Derived from small-scale studies (typically conducted in healthy volunteers or patients with advanced/severe conditions). Its primary objective is to determine safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetics, the maximum tolerated dose (MTD), and the recommended dose for subsequent phases.
3. Phase II clinical evidence: Built on trials in medium-sized cohorts of patients with the target disease. Its purpose is the preliminary evaluation of therapeutic efficacy (e.g., tumor shrinkage, progression-free survival, or surrogate endpoints), refinement of the appropriate dosing regimen, and further safety monitoring.
4. Phase III clinical evidence: Evidence originating from large-scale, multicentre, usually randomized, controlled trials. Its goal is to confirm the clinical efficacy and safety of the new treatment compared to the existing standard of care or placebo, frequently based on hard clinical endpoints (such as overall survival), which serves as the foundation for marketing authorization.