Phases of Clinical Trials

Clinical trials are the best way to learn what works in treating diseases like cancer. Clinical trials occur in different “phases” that build on one another. Each phase is designed to answer certain questions and keep participants as safe as possible.

Knowing the phase of a clinical trial is important because it can give you an idea about how much is known about the treatment being studied. While there are many types of clinical trials, this information focuses on clinical trials for treatments for people with cancer.

Phase 0 clinical trials: Is this treatment worth studying more?

Phase 0 studies aren’t like the other phases of clinical trials. The purpose of this phase is to help speed up the drug approval process. This may help save time and money that would have been spent in later clinical trial phases. They’re not a required part of testing a new treatment.

They might test:

• Whether the drug reaches the tumor
• How the drug acts in the human body
• How cancer cells in the human body respond to it

Key points of phase 0 clinical trials

• Phase 0 studies only use small doses of a new medicine for a short time in a few people, often fewer than 15.
• People in these studies might need extra tests such as biopsies, scans, and blood samples as part of the process.
• Unlike other phases of clinical trials, there’s almost no chance the people in phase 0 trials will benefit. The benefit will be for other people in the future.
• Because medicine doses are low, there’s less risk to those in the trial.

Phase I clinical trials: Is the treatment safe?

Phase I studies are done to find the highest dose of a new treatment that can be given safely without causing severe side effects. These studies also help to decide on the best way to give the new treatment.

Key points of phase I clinical trials

• The first few people in the study get a very low dose of the treatment and are watched very closely. If there are only minor side effects, the next few participants get a higher dose. This process continues until doctors find a dose that’s most likely to work while having an acceptable level of side effects.
• Phase I trials also look at what the treatment does to the body and what the body does with the treatment.
• Safety is the main concern. The research team keeps a close eye on the people and watches for any severe side effects. Because of the small numbers of people in phase I studies, rare side effects may not be seen until later phases of trials when more people receive the treatment.
• Placebos (inactive treatments) are not used in phase I trials.
• Phase I trials usually include a small number of people (usually 10-30).
• Phase I trials usually include people with different types of cancer.
• These studies are usually done at major cancer centers.

Phase I trials carry the most potential risk. But phase I studies do help some patients. For those with life-threatening illnesses, weighing the potential risks and benefits carefully is key. Sometimes, people choose to join phase I trials when all other treatment options have already been tried.

Phase II clinical trials: Does the treatment work?

If a new treatment is found to be safe in phase I clinical trials, a phase II clinical trial is done to see if it works in certain types of cancer.

Phase II trials may look to see if:

• The cancer shrinks or disappears.
• There’s a longer period of time where the cancer doesn’t get any bigger.
• There’s a longer time before the cancer comes back.
• The treatment improves the quality of life of people who receive it.
• People who get the treatment live longer than those who don’t receive it.

Key points of phase II clinical trials

• A group of 25 to 100 patients with the same type of cancer get the new treatment in a phase II study. They’re treated using the dose and method found to be the safest and most effective in phase I studies.
• Usually in phase II clinical trials, everyone gets the same dose. But some phase II studies randomly assign people to different groups. These groups may get different doses or get treatment in different ways to see which provides the best balance of safety and response.
• Placebos (inactive treatments) are not used in phase II trials.
• Phase II studies may be done at major cancer centers, community hospitals, or doctors’ offices.
• Larger numbers of people get the treatment in phase II trials, so less common side effects may be seen.

If enough people benefit from the treatment, and the side effects aren’t too bad, phase III clinical trials may begin.

Phase III clinical trials: Is it better than the standard treatment?

Phase III clinical trials compare the safety and effectiveness of the new treatment against the current standard treatment. Side effects of the treatments are also compared. If the clinical trial is successful, the new treatment may be approved for use outside of clinical trials.

Because doctors do not yet know which treatment is better, study participants are often picked at random (randomized) to get either the standard treatment or the new treatment. When possible, neither the doctor nor the patient knows which of the treatments the patient is getting. This type of study is called a double-blind study. For more information, see Things to Consider Before Taking Part in a Clinical Trial.

Key points of phase III clinical trials

• Most phase III clinical trials include many patients, at least several hundred.
• These studies are often done in many places across the country (or even around the world) at the same time.
• Phase III clinical trials are more likely to be offered in local community hospitals and doctors’ offices.
• These studies tend to last longer than phase I and II studies.
• Placebos (inactive treatments) may be used in some phase III studies. But if there’s a treatment available that works (the standard treatment), a participant can expect to receive it. It would be unethical otherwise.

As with other trials, people in phase III clinical trials are watched closely for side effects. Treatment is stopped if they’re too hard to manage.

Phase IV clinical trials: What else do we need to know?

Treatments approved by the US Food and Drug Administration (FDA) are often watched over a long period of time in phase IV studies. Even after testing a new treatment on thousands of people, some questions may still need to be answered. For example:

• A treatment may get FDA approval because it was shown to reduce the risk of cancer coming back. But does this mean that those who get it are more likely to live longer?
• Are there rare side effects that haven’t been seen yet?
• Are there side effects that only show up after a person has taken the treatment for a long time?

Key points of phase IV clinical trials

• Phase IV trials look at treatments that are already available for doctors to prescribe for patients.
• These clinical trials may involve thousands of people.
• This is often the safest type of clinical trial because the treatment has already been studied a lot and has likely been given to many people. Phase IV studies look at safety over time.
• These clinical trials may also look at other aspects of the treatment, such as quality of life or cost effectiveness.

You can get the medicines used in a phase IV trial without being in a study. And the care you would get in a phase IV study is much like the care you would get if you were to get the treatment outside of a trial. But in phase IV studies, you’re helping researchers learn more about the treatment and doing a service to future patients.

How does a new treatment make it into a clinical trial?

Before a clinical trial can start, the research must be approved. An investigational new drug (IND) application must be filed with the FDA when researchers want to study a new treatment in humans. The IND application must contain information like:

• Results from preclinical (laboratory) studies, so the FDA can decide if the treatment is safe for testing in people.
• How the treatment is made, who makes it, what’s in it, how stable it is, and more.
• Detailed plans for the proposed clinical trial that ensure that people are not exposed to needless risks.
• Details about the clinical trial team that prove they have the knowledge and skill to run the proposed clinical trial.

The research team must commit to getting informed consent from everyone in the clinical trial. They must plan to get the study reviewed by an institutional review board (IRB) and follow all the rules required for studying investigational new treatments.

How does a new treatment get approved by the FDA?

When phase III clinical trials (or sometimes phase II trials) show a new treatment is more effective or safer than the standard treatment, a New Drug Application (NDA) is submitted to the FDA for approval. The FDA reviews the results from the clinical trials and other relevant information.

If approved, the new treatment often becomes the standard of care, and newer treatments may be tested against it before they can be approved.

If the FDA feels that more evidence is needed to show that the new treatment's benefits outweigh its risks, they may ask for more information or even require that more studies be done.