Clinical-Trial Phases Explained

Why phases exist

Treatments are tested in people in steps so that safety questions are answered before large groups are exposed, and effectiveness questions are answered with enough people to mean something. The phases below are how the U.S. FDA and others describe drug testing. This page is information only. It is not advice about joining a trial. Different regulators and different product types, such as devices and behavioral programs, can work differently.

The four phases

The sizes and lengths come from the FDA's description of the process. [1] Other sources give slightly different ranges. The NIA, for instance, describes Phase 1 as around 20 to 80 people and Phase 2 as around 100 to 300. [2] Treat all of these as rough guides, not rules.

Phase 1

Phase 1 studies are the first step in testing a new treatment in humans. They test safety, side effects, best dose and timing, and sometimes the best way to give the treatment. [3] They are closely monitored and gather information about how a drug interacts with the human body. [1] Participants may be healthy volunteers or, for some conditions such as cancer, patients. [1] The NHS says researchers start with small doses and only increase them if volunteers do not have side effects, or only minor ones. [4] A Phase 1 study cannot show that a treatment works.

Phase 2

Phase 2 studies test whether a new treatment works for a certain disease, and also give more information about safety. [5] The FDA notes these studies typically involve a few hundred patients and are not large enough to show whether the drug will be beneficial. [1] A positive Phase 2 result is a reason to run a larger study, not a verdict.

Phase 3

Phase 3 studies test safety and how well a treatment works compared with a standard treatment. [6] The FDA says they are designed to demonstrate whether a product offers a treatment benefit to a specific population, and because they are larger and longer, they are more likely to show long-term or rare side effects. [1] Before filing a marketing application, a developer must have adequate data from two large, controlled clinical trials. [1] Even so, a Phase 3 result applies to the group and conditions studied.

Phase 4

Phase 4 trials take place after the FDA has approved the drug or device. [1] They study side effects over time and look for ones not seen in earlier trials. [7] The NHS notes they are not required for every medicine. [4]

How many treatments get through

The FDA reports that approximately 70% of drugs move from Phase 1 to the next phase, approximately 33% from Phase 2, and approximately 25 to 30% from Phase 3. [1] These are FDA figures for the drug process, not a promise about any one product.

What a phase does not tell you

• A phase is not an approval. Approval is a regulator's separate review of all the data. [8]
• A registered or running trial proves nothing about effectiveness. See registered trials vs published results.
• Phase labels fit drug-style testing best. Not every wellness product or technology is tested this way. Trials of behavior change follow similar steps but are not regulated by the FDA. [2]
• Early success may not hold. Small trials tend to show larger effects: treatment effects averaged 48% larger in trials with fewer than 50 patients than in trials of 1,000 or more. [9]
• Design matters too. Many trials compare a treatment group with a control group, which receives a standard treatment or a placebo. [4]

Where the phase fits in the bigger picture

Trials in people come after laboratory and animal work. See cell studies vs animal studies vs human trials and discovery vs clinical application. If you are considering joining a trial, read clinical trials explained for participants and ask your own clinician.