Phases of clinical trials
- Concept
A new medicine moves through phases: safety in a few volunteers first, then efficacy in hundreds, then thousands of patients and, after approval, monitoring.
What it is
The clinical development of a medicine moves through phases, each with its own question. Phase I studies safety and the dose range in a few volunteers; phase II explores efficacy and adverse effects in a few hundred patients; phase III confirms efficacy against the standard in hundreds to thousands of patients and supports approval; phase IV takes place after marketing and monitors safety in real practice. The optional phase 0 gives microdoses to very few people to study how the drug behaves in the body.
Worked example
- Approximate FDA figures: about 70% of drugs move on from phase I, 33% from phase II and 25-30% from phase III.
- Of 100 drugs entering phase I, about 100 × 0.70 = 70 reach phase II.
- About 70 × 0.33 ≈ 23 reach phase III.
- About 23 × 0.25 ≈ 6 to 23 × 0.30 ≈ 7 get through phase III.
- Reading: of every 100 candidates tested in people, only about 6 or 7 go on to seek approval.
- An adverse effect in 1 of 10 000 patients: a 95% chance of seeing it at least once needs about 3 × 10 000 = 30 000 people.
- A phase III trial of 3 000 patients will rarely detect it: that is why phase IV exists.
The phases at a glance
| Phase | Participants | Main question |
|---|---|---|
| 0 (exploratory) | Very few | How does a microdose behave in the body? |
| I | About 20 to 100 people, often healthy volunteers | Is it safe, and in what dose range? |
| II | Up to several hundred patients | Does it work, and what adverse effects does it have? |
| III | About 300 to 3 000 patients or more | Is it effective against the standard or placebo? |
| IV | Thousands of patients in real practice | Do rare or late effects appear after approval? |
Markers
- Phase I
- Phase II
- Phase III
- Phase IV
In practice
- The rule of three: if no event was seen in n patients, the upper limit of the 95% CI for the risk is about 3/n.
- In Colombia, post-marketing pharmacovigilance is coordinated by INVIMA; health professionals can report adverse events.
Common pitfalls
- Thinking that an approved medicine already has all its adverse effects known.
- Confusing phase IV with a bigger phase III trial: phase IV comes after approval and often includes observational studies and spontaneous reports.
Test yourself
Think of the answer, then tap the question to see it.
What is the main aim of phase I?
To assess safety and the tolerable dose range in a small group of healthy volunteers or patients.
Which phase usually detects very rare adverse effects?
Phase IV (post-marketing), because only then is the drug used by thousands or millions of people.
A phase III trial with 1 500 patients saw no case of an adverse effect. What is the highest plausible risk?
By the rule of three, about 3/1 500 = 0.2% (1 in 500) as the upper limit of the 95% CI.
Connections
Educational content on epidemiological and statistical methods; the examples use made-up numbers to teach the calculation. Not a clinical or legal guide: current Colombian rules are in the official sources.
Sources: Step 3: Clinical Research (U.S. Food and Drug Administration, 2018); Clinical trials (World Health Organization, 2026).
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Representative model, for educational purposes only.