A phase 1, 2 or 3 trial is a step in the process of investigating a new treatment before it becomes widely available. Phase 1 mainly looks at safety and dosing in a small group, phase 2 looks at whether the treatment seems to have an effect in the disease in question, and phase 3 compares the treatment on a large scale with existing standard care. Only after a successful phase 3 can a drug be approved for use outside of a research setting.
The phases follow one another because each step answers a different question. Phase 1 tells us something about safety in a handful of people, not about effectiveness in a larger group of patients. This is precisely why news about a promising phase 1 study should be read with caution: the chance that a drug that passes phase 1 will ultimately also be approved is relatively small. Most substances that start in phase 1 do not reach phase 3.
What happens in phase 1
In phase 1, a new treatment is tested in humans for the first time, often in twenty to one hundred participants. Researchers look at side effects, how the body processes the substance and what dose is still safe. In some diseases, such as certain forms of cancer, patients also participate instead of healthy volunteers, because the substance is too risky to test in healthy people. A positive signal in phase 1 therefore mainly means: the substance seems manageable enough to investigate further, not that it works.
What happens in phase 2
Phase 2 revolves around the question of whether the treatment actually has an effect in the condition it is intended for. Usually several tens to a few hundred patients are involved. Researchers gather initial evidence of effectiveness and closely monitor side effects in a larger group than in phase 1. This phase provides an indication, but the numbers are usually still too small and the design often not strict enough to draw firm conclusions. Those who want to know more about how to assess such a study design can find background information in the article treatment methods and their level of evidence per disease.
What happens in phase 3
Phase 3 is the largest and most expensive phase, often with hundreds to thousands of participants, spread across multiple hospitals and sometimes multiple countries. The new treatment is compared here with existing standard treatment or with a placebo, usually in a design where it is not known who receives which treatment. This comparison, combined with the larger numbers, makes it possible to say with more certainty whether a treatment actually works better and how the side effects compare to the benefit. Only on the basis of convincing phase 3 results do regulatory authorities such as the European Medicines Agency assess whether a drug is approved.
Why a phase 1 result still says little
News reports on research regularly report a phase 1 study with a hopeful outcome. It is understandable that such news attracts attention, especially for those living with a disease for which there are few treatment options. Yet it holds true: the earlier the phase, the smaller the group, the more preliminary the conclusion. A drug that proves safe in phase 1 must still show that it works in phase 2, and that it works better than what already exists in phase 3. Therefore, researchers only consider after phase 3, and sometimes only after longer follow-up studies, whether a treatment can change standard care.
How you can use this knowledge
If you read news about research into a treatment for your disease, it's useful to check which phase the study is in. That immediately puts the outcome into perspective, without denying the value of the research. Codex mentions the level of evidence for publications, so it's clear how well-supported an outcome is. Anyone who wants to know exactly where that information comes from and how it was obtained can read more on the page about how Codex works. For questions about what is and isn't included when using Codex, there's also an overview with answers to frequently asked questions.
Whether a new research result means anything for your own situation is a question best discussed together with your doctor. They can compare the phase of the research, the group studied and your own situation.
Codex collects per disease the treatments and underlying research, including the phase that studies are in, entirely free and without requiring an account. Anyone who creates an account can save publications with their own notes. Curious how that looks for a specific disease? A free account creation takes a few minutes.