Phases of Clinical Trials in Drug Development

Overview & position within new-drug development

• Definition — A clinical trial is a prospective, ethically designed investigation in human subjects to objectively discover, verify or compare the results of two or more therapeutic measures — it characterises the drug's pharmacokinetics & pharmacodynamics in humans and establishes its efficacy and safety before marketing.
• The four phases — Human drug evaluation is conventionally divided into four temporal phases (Phase I → IV), sequenced so results of earlier studies inform later ones. They are divisions of convenience in a single continuously expanding process — from a few closely-observed subjects, to hundreds, to thousands.
• Pre- vs post-marketing — Phases I–III are pre-marketing (establish safety + efficacy to support the marketing application); Phase IV is post-marketing (surveillance after approval). The phased structure embodies a risk-minimisation logic — few subjects under close supervision first, larger numbers later.
• Steep attrition — Of ~5,000–10,000 screened compounds, ~250 enter preclinical testing, ~5 enter clinical trials, and only ~1 is ultimately approved. Overall timeline synthesis → approval is ~10–15 years, at an estimated cost of US $1–4 billion per new molecular entity.
• Surrounding milestones — Synthesis (1–2 yr) → preclinical studies under GLP in ≥2 species (2–4 yr) → IND application (FDA has 30 days to review before any human dosing) → Phase I–III clinical studies (3–10 yr) → NDA/BLA review & marketing permission (0.5–2 yr) → Phase IV.