What are clinical trial phases?

In order to reach patients, every potential medical intervention must make its way through a rigorous approval process, passing through clinical trial phases. Each clinical trial phase has a different goal and separate hurdles to clear before a potential new treatment or medical device can move forward.

The process begins when researchers develop new drugs in a lab. Before an intervention reaches any clinical trial stage, scientists research ideas in what is called the discovery phase. This step can take from three to six years. Typically, researchers will test drugs on animals before moving on to the first stage of clinical testing in humans. Once approved, researchers, pharmaceutical companies, or biotechs can begin enrolling volunteers in a phase I trial.

At the end of the day (or decade), it takes approximately ten years for a new treatment to complete the journey from initial discovery to the marketplace. Clinical trials alone take six to seven years on average to complete.

Phase I clinical trials

Phase I clinical trials test whether drugs are safe to use in humans. These trials are typically small — they enroll approximately 20 to 100 volunteers. Some phase I clinical trials only look for healthy volunteers, who may be compensated for participating. Others accept those with the condition the drug aims to target. While the drug may help symptoms, a phase I trial’s goal is to prove safety, but not necessarily how effective the drug or device is. This trial phase can last anywhere from several months to a year. 

Doctors start the trial by administering a very small dose of the drug and measuring how it's absorbed, metabolized, and excreted in the body. Researchers also check for side effects. As researchers increase dosage, they continue to measure side effects. If researchers find the drug to be safe, it then moves forward to phase II. Around 70% of experimental drugs move past this stage.

Phase II clinical trials

Phase II clinical trials test both the safety and effectiveness of a drug or medical device. Trials in this stage can last from several months to a few years, and recruit up to several hundred patients with the condition to take part.

Many phase II clinical trials are randomized, which means one group of participants receives the study drug, while the other group receives a placebo or an existing, standard treatment. Other phase II studies are "blinded," which means that neither the researchers nor the participants know who received the study drug.

In this phase, the drug has to be found safe and effective in order to move forward to phase III, which is typically only 33% of drugs or interventions. 

Phase III clinical trials

Phase III clinical trials are usually the largest — these trials test a potential treatment in hundreds to thousands of people in a randomized, blind study. This testing phase can last several years as the FDA gathers thorough data about the drug's effectiveness and potential side effects.

Once a potential treatment or device makes it through this stage, a pharmaceutical company can request FDA approval to start marketing the drug. A pharmaceutical company may submit a New Drug Application (NDA) or a biologics license application (BLA) to the FDA. The FDA then reviews results from all stages of the trial to determine whether it will approve the drug and allow the pharmaceutical company to begin marketing it to the public.

Sometimes, it may require that additional studies be done or that a hearing be held to decide whether a drug’s benefits outweigh its risks. If all looks good, the drug is approved and the pharmaceutical company can bring it to market.

During a public health emergency, such as the current COVID-19 pandemic, the FDA may issue an Emergency Use Authorization (EUA), which is a mechanism to facilitate the availability and use of medical countermeasures, including vaccines. While the process for COVID-19 vaccines has been greatly accelerated, the clinical trials being conducted adhere to the same rigorous standards set forth by the FDA for other potential treatments and devices. 

Phase IV clinical trials

Also known as “Post-Approval Research and Monitoring”, Phase IV takes place after a drug or device has been approved. In this phase, pharmaceutical companies monitor a drug's long-term impact. This phase is crucial, because it may take a few years for longer-term side effects to appear.

Is a clinical trial right for you?

When you're considering taking part in a clinical trial, ask the study team about the schedule of the trial. Some trials may last for several years, but only require visits every few months, for example. Other trials may require more frequent visits, or for participants to make entries in an e-diary or paper diary in-between visits. You'll want to weigh the potential benefits of participation against the time it may require of you. Some clinical trials reimburse you for participating in a trial, and others pay for travel.

If you choose to join a clinical trial, you're free to leave at any time for any reason, even before the trial is completed. If researchers aren't seeing the results they were hoping for, some trials also end early. 

The clinical trial process is long — and it's set up that way so that by the time drugs reach the public, they have been thoroughly evaluated. Without enough volunteers, up to 80% of clinical trials are delayed. Start looking for a clinical trial near you and help research move forward below.