Clinical trials are done in several progressive phases, with each phase aiming to answer different questions.  

Phase I: Is it safe?  Phase I clinical trials are the first step in testing a new intervention in human participants. The focus in this first step is on ensuring safety and identifying side effects. A phase I trial allows a clinical researcher to see how the new intervention affects the human body and to find the best dosage range and dose schedule that can be given safely without serious side effects.

Phase II: Does it work?  Phase II clinical trials are the second step in the testing process, where researchers look at how the intervention affects the disease and whether the intervention is effective. The intervention is now tested in a larger group of human participants (up to several hundred people), using the dosage range and schedule determined to be safe in the phase I trial. Researchers also continue to evaluate the safety of the intervention in this stage.

Phase III: Is it better?  Phase III clinical trials are done only after the results of the phase II trial show promise. These trials are done in an even larger number of human participants (300 to 3,000 people) who are assigned to different groups (also known as arms). Some of the participants are assigned to receive the intervention (the study group), while others are assigned to receive a commonly used intervention or the current standard-of-care intervention (the control group). Participants do not get to choose which group they are assigned to. Rather, the researchers assign them to groups randomly; this is known as a randomized clinical trial. Comparing the results from the study group versus the control group allows the researchers to see whether the effectiveness and safety of the new intervention are better, the same, or worse than other interventions already being commonly used.

Phase IV: Which questions remain to be answered?  Phase IV clinical trials are done after the new intervention — which proceeded successfully through phases I, II, and III — has been approved by the Food and Drug Administration (FDA). These trials are done with several thousand participants. At this point, even though the intervention is now available for patients to receive from their doctors, patients can still participate in phase IV trials to help researchers answer important remaining questions. For example, a phase IV trial might look at the intervention’s safety over a longer period of time, its cost effectiveness, or whether it affects patients’ longevity or quality of life.