The phases of clinical trials are the stages through which an investigational drug or medical product is tested in people, moving from small safety studies in Phase 1 to large comparison studies in Phase 3 and monitoring after approval in Phase 4.
The phase framework applies across medicine, including the work covered in stem cell research, and it explains why a promising lab result is not the same as an approved treatment.
Why clinical research is split into phases
Preclinical work answers basic safety questions, but the FDA notes that it is not a substitute for studies of how a drug interacts with the human body. Clinical research refers to studies, or trials, that are done in people.
Each trial follows a written study plan called a protocol. Before a trial begins, researchers decide who qualifies to participate, how many people will take part, how long the study will last, whether there will be a control group, how the product is given and at what dose, and how the data will be analysed.
Every trial also has eligibility criteria. The National Cancer Institute explains that these criteria help reduce the medical differences among people in the trial and reduce the risk that people will be harmed. When participants are alike in specific ways, researchers can be more certain that results are due to the intervention being tested and not to other factors.
Phases exist so that risk and scale grow together. A product that looks unsafe in a small group never reaches a large one, and a product that shows no signal in a mid-sized group does not move on to an expensive late-stage study.
Before Phase 1: the Investigational New Drug application
In the United States, developers must submit an Investigational New Drug (IND) application to the FDA before beginning clinical research. The FDA says the application must include animal study and toxicity data, manufacturing information, clinical protocols, data from any prior human research and information about the investigator.
The FDA review team has 30 days to review the original IND submission. The FDA can place a clinical hold, which delays or stops the investigation, though a clinical hold is rare. If the FDA is satisfied that the trial meets Federal standards, the applicant is allowed to proceed with the proposed study.
- About 70% of drugs move from Phase 1 to Phase 2: 70%
- About 33% of drugs move from Phase 2 to Phase 3: 33%
- About 25-30% of drugs move from Phase 3 onward: 25-30%
- FDA has 30 days to review an original IND submission: 30 days
Phase 1: safety and dosage
Phase 1 is the first time a new product is given to people. According to the FDA, these studies involve 20 to 100 healthy volunteers or people with the disease or condition and last several months. Their purpose is safety and dosage.
Researchers learn how much of a product the body can tolerate, what its acute side effects are and how it behaves in the body. If a product is intended for cancer patients, Phase 1 studies are run in patients with that type of cancer rather than in healthy volunteers.
The FDA reports that approximately 70% of drugs move to the next phase.
Phase 2: early signs of effect and more safety data
Phase 2 studies give the product to a group of patients who have the condition it is meant for. Participants number up to several hundred people, and the studies run from several months to 2 years, with efficacy and side effects as the purpose, as described by the FDA.
These studies are not large enough to show whether a product will be beneficial. Instead, they provide additional safety data that researchers use to refine research questions, develop methods and design Phase 3 protocols. The same FDA page puts the share of drugs that move on from this phase at approximately 33%.
Phase 3: comparing against the standard
Phase 3 studies, sometimes called pivotal studies, are designed to show whether a product offers a treatment benefit to a specific population. The FDA lists 300 to 3,000 participants who have the disease or condition and a length of 1 to 4 years.
Because these studies are larger and longer, they provide most of the safety data and are more likely to reveal long-term or rare side effects that earlier studies could have missed. The FDA reports that approximately 25-30% of drugs move to the next phase.
The National Cancer Institute explains that in a Phase 3 trial researchers compare the treatment with the current standard therapy to see which works better, and that participants are randomly assigned to one of the treatments. Randomization, in which people are assigned to groups by chance alone, helps prevent bias, meaning results affected by human choices or other factors unrelated to the treatment being tested.
The NCI adds that results from Phase 1 to 3 trials are used to make decisions about approving new treatments, or existing treatments for new conditions, by agencies such as the US Food and Drug Administration.
In the NCI’s summary, the early phases (Phase 1 and 2) test for safety, such as what the side effects are and what a safe dose is, while the later phases (Phase 3 and 4) compare the treatment with current standard treatments. That split is a useful rule of thumb: early phases ask whether a product is safe enough to keep studying, and later phases ask whether it performs better than what patients already have.
Phase 4: monitoring after approval
Phase 4 trials are carried out once a drug or device has been approved by the FDA, during post-market safety monitoring, according to the FDA. The NCI describes them as looking at long-term safety and effectiveness in large, diverse populations as more people use the product over a longer period.
Approval is therefore not the end of evidence gathering. It is a point at which the available evidence was judged sufficient, with further monitoring continuing afterwards.
Reading phases when a therapy is still investigational
The phase label tells a reader what question a study was built to answer. A Phase 1 result speaks to safety and dose, not to whether a product works. A Phase 2 result is an early signal at best, since the FDA states these studies are not large enough to show whether a drug will be beneficial.
That distinction matters for new fields such as cell-based medicine, where news coverage often describes early-stage studies in strong language. The practical guide to finding and reading registered studies is covered in stem cell clinical trials, and the background on how the field reached its present stage is in the history of stem cell research.
Whether any particular study or treatment is appropriate for a specific person is a question for a licensed physician who knows that person’s situation.
Frequently asked questions
What is the main difference between Phase 1 and Phase 3?
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Phase 1 is a small, closely monitored study focused on safety and dosage, while Phase 3 is a much larger study that tests whether a product offers a benefit to a specific population and provides most of the safety data, according to the FDA.
Does a Phase 4 trial mean a product is still experimental?
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No. Phase 4 trials take place after the FDA has approved a drug or device, as part of post-market safety monitoring.
Why are participants randomly assigned in later phases?
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The National Cancer Institute explains that random assignment by chance alone helps prevent bias, so that differences between groups are more likely to reflect the treatment rather than human choices.
Do all products move through every phase?
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No. The FDA reports that only a share of drugs move from each phase to the next, approximately 70% after Phase 1, approximately 33% after Phase 2 and approximately 25-30% after Phase 3.
