Clinical trial phases

Drugs are tested in people in stages. Each stage asks a narrower question, enrols more participants and runs longer. The FDA's own outline of the phases:

Multiply the success rates and most drugs that enter phase 1 never reach approval.

Before phase 1

A compound first goes through laboratory and animal studies, and the sponsor files an Investigational New Drug application with the FDA before any person receives it. Animal data guide the first human dose and flag toxicity. They often fail to predict effects in people, which is why the phases exist at all.

What each phase can and cannot tell you

Phase 1 finds a tolerable dose range and measures pharmacokinetics. It says almost nothing about benefit.

Phase 2 gives the first controlled estimate of effect and tests several doses. Groups are small, so estimates are imprecise and rare side effects are invisible. The retatrutide phase 2 trial in obesity enrolled 338 adults across seven arms. Its 12 mg arm lost a mean 24.2 percent at 48 weeks against 2.1 percent on placebo, a striking number from a few dozen people per arm.

Phase 3 is the confirmation, in hundreds to thousands of people, usually placebo-controlled, at the doses that will go on the label. STEP 1 (1,961 people) and SURMOUNT-1 (2,539 people) are phase 3 trials. Some phase 3 trials are cardiovascular outcome trials, like SELECT with 17,604 people, which run for years and report a hazard ratio.

Phase 4 follows the drug after approval. Rare harms often surface here, in far larger and more varied populations than any trial.

Reading a headline

A press release saying a drug "met its primary endpoint" in phase 3 is a company announcement. The peer-reviewed paper, with full methods, comes later, and regulators review the full data before approval. Phase 2 results often shrink in phase 3, as more varied patients enrol and the trial runs longer. When a page on this site reports a number, it says which phase and whether it is peer reviewed. The retatrutide page tracks its phase 3 programme.

Compounds that have only been tested in animals have not entered phase 1. That is most of the research peptide list, and the compound pages say so.

The app's compound library grades each compound by how much human evidence exists, from approved drugs with phase 3 and outcome trials down to compounds with animal data only.

Related terms: placebo-controlled trial, surrogate endpoint, estimand, hazard ratio. Back to the glossary.