Evaluating biomedical literature requires discerning the pyramid of evidence.
Preclinical research (in vitro cell cultures and animal models) provides vital mechanistic proof-of-concept regarding receptor binding and safety margins. However, species differences in receptor density and metabolism mean preclinical findings cannot be assumed to translate directly into human efficacy.
- Phase 1: Safety, tolerability, and pharmacokinetics in small cohorts.
- Phase 2: Dose-ranging and preliminary efficacy in target populations.
- Phase 3: Large-scale multicenter randomized controlled trials (e.g. the STEP and SURMOUNT programs) comparing the compound against placebo or standard of care.