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The different phases of clinical trials

Clinical trials are run in multiple steps, called phases, that build on one another. Each phase helps answer different questions about the new treatment.

While the treatment’s safety and efficacy is monitored throughout each phase, the phase a clinical trial is in roughly represents how much is known about the treatment being studied. The phase that a clinical trial is in can be a factor to consider when finding and deciding between different studies you might want to participate in.

You're never required to participate in all phases, and in most cases, you can join at any phase. For example, you could enroll in the phase 3 clinical trial of a specific treatment even if you didn’t participate in its phase 2 clinical trial.

Note: While both cancer stages and clinical trial phases use the same numbers (1,2,3, and 4), the two numbers are different. Every trial has a different set of criteria that determines who can participate in the study, but the stage of cancer doesn't necessarily match which clinical trial phase is a good fit.

Trial-Phases

Phase 1: Is the new treatment safe?

Phase 1 clinical trials are usually the first to involve people, and help doctors learn if a new treatment is safe. If you join a phase I clinical trial, you could be one of the first people to get a promising new drug or treatment.

In this phase, the medical team collects information on:

  • The most common side effects
  • How your body responds to the treatment
  • What dose of the treatment works the best (in the case of a drug)

The first few people in a phase 1 trial often get a very low dose of the treatment and are followed closely. If there are only minor side effects, the next few participants might get a higher dose. This continues until doctors find the dose that's most likely to work well.

Phase I clinical trials last several months to a year, and usually have 10 to 80 participants. All information gathered from the phase 1 trial helps researchers design the Phase 2 study.

Phase 2: Does the treatment work?

If the phase 1 clinical trial shows the treatment is reasonably safe, it moves on to a phase 2 clinical trial to see if it works for treating the condition. A larger group of 100-300 participants typically receive the amount of treatment that was found to be the most effective in the phase 1 trial. Phase 2 trials usually last over the course of several months to two years.

In some trials, the patients participating will receive different treatments. For example, one group could receive the FDA approved treatment that they would be receiving if they didn't participate in the clinical trial, and another would receive the new treatment being studied in the trial.

The response the doctors look for in patients depends on the goal of the treatment. For example, in a cancer clinical trial, it may mean the cancer disappears completely, or that patients on the new treatment live longer than they would have been expected to without the treatment. In other studies, especially for chronic conditions, the benefit may be an improved quality of life.

If the treatment seems to be effective for treating the condition, the study will likely move on to a Phase 3 trial.

Phase 3: Is the treatment better than what's currently available?

Treatments that have been shown to work in phase 2 trials typically need to be evaluated in one more phase before they’re approved for general use. This happens in phase 3 clinical trials, where doctors compare the new treatment with the best treatment known today (also called the "standard treatment").

To do this, they need to assign people to different groups as part of the clinical trial. The patients in each group get a specific treatment, and the treatments are different between each of the groups. This helps them see if the new treatment works better than the standard treatment, has fewer side effects, or both. Because doctors don't know which treatment is better yet, study participants are often assigned to the groups randomly, and neither the doctors nor patients know which treatment they're on. Placebos may be used in some trials, but are rarely used alone if there's already an approved treatment that has been shown to work.

These trials can take many years, and have up to several thousand volunteers who participate. If the results show that the treatment works well, the research team can then apply for FDA approval, to make the treatment available to the general public.

Getting the treatment FDA approved

When phase 3 clinical trials (or sometimes phase 2 studies) show a new drug is more effective and safer than the current standard treatment, a New Drug Application (NDA) is submitted to the Food and Drug Administration (FDA) for approval. The NDA, which includes data from all the pre-clinical and clinical studies, is reviewed by the FDA.

Based on the review, the FDA decides whether or not to approve the treatment for patients with the condition the drug was tested on (to be used in a different condition, additional clinical trials have to be done).

If the FDA believes that more evidence is needed to show that the new treatment's benefits outweigh its risks, it will ask for more information or even require that more studies be done. If approved, the new treatment often becomes a standard of care, and newer treatments must often be compared to it before being approved.

Phase 4: What else can we learn about the treatment?

Even after being approved by the FDA, treatments are still often watched for a long period of time in phase 4 studies. Although the medicine has been tested in thousands of people, additional studies can help show more about the treatment, such as very long term side effects. These studies may also look at other traits of the treatment, such as quality of life or cost effectiveness.

For example, a stem cell treatment may get FDA approval because it was shown to improve the function of individuals with knee osteoarthritis. But the medical teams may want to know if there are any rare side effects that haven’t been seen yet, or side effects that only show up after a person has had the therapy for a long time. These types of questions can take many years to answer, and are often answered in phase 4 clinical trials.

Phase 4 studies are generally the safest type of clinical trial because the treatment has already been studied for a long time, and might have already been used in many people. While you can access the treatments in a phase 4 trial without enrolling in the study, participating can allow you to access an already FDA approved treatment at little to no cost, since the sponsor of the study will typically cover the cost of the therapy completely. Additionally, volunteering can help doctors learn more about the treatment and help patients in the future.