Clinical Trials Consist of Four Phases: What are they?

"Clinical research" is a term that many people have heard, but not enough know about. Clinical research consists of numerous steps, processes, and phases to collect data about the efficiency and safety of a potential new treatment option. The information gathered helps researchers and doctors make sure everything is up to the required standards before a drug becomes available to the public. For this article, we specifically mention the phases that a drug, or medication, goes through; however, clinical research also includes medical devices, therapies, and procedures.

Before getting into detail about the four main phases of clinical research and what each entails, a recent addition is not something to overlook. Officially introduced in 2006 by the US Food and Drug Administration (FDA) and the Pharmaceutical Research and Manufacturers of America (PhRMA), Phase 0 clinical trials are aimed to determine if an experimental drug is harmful to humans in any way.

They are not used too widely nor are they required by the FDA, but Phase 0 trials do help streamline the drug approval process because they allow researchers to decide whether to move forward with the drug before being tested in a larger sample size of participants. In this phase, the likelihood of any volunteer seeing a benefit from participation is slim to none because of the small dosage administered. On the plus side, there is also a smaller risk for the same reasons. The higher benefit and risk levels will be seen by those taking part in future phases.

Speaking of the future phases, each one is considered a separate trial despite being for the same drug. The reason for the separation is to receive updates along the way to determine if the testing should continue. After each phase, the individual responsible for conducting the trial, known as a principal investigator, is required to submit all findings to the FDA for review and approval.

At this point, you have heard the term phase numerous times, but what are the different phases of clinical trials? What do they entail? What is the purpose of these different phases?

Phase I

Phase I studies are those that generally involve people for the first time. In this phase, researchers see how the human body reacts to the drug that is being studied. Participants will include a small (typically a couple dozen) number of people. For Phase I clinical trials, the organizations conducting the study will attempt to find the highest dose of a new drug that can be given to the volunteers without serious side effects. In addition, they are used to help determine the best method for administering the drug, whether it be in a pill, injection, or otherwise.

In a Phase I study, the dosage received will vary based on when a volunteer signs up. The first few people involved receive a low dose of the experimental treatment to monitor the possible side effects. Should they be minor or non-existent, the next set of participants will receive a higher dose. This continues throughout the study as new patients are added until the desired effect of the drug is achieved, or the side effects become too severe for the participants. Phase I trials do not involve any placebo and are done to study the effects of the drug. Because of the unknown nature of how the drug will interact with people, Phase I trials often carry the most risk. That said, they can also provide the most benefit to researchers as they continue the development of the treatment. According to CenterWatch, about 70% of all the experimental drugs at this stage pass onto Phase II.

Phase II

Phase II clinical trials begin after a drug is determined to be safe for human use in a Phase I trial. Phase II studies can involve hundreds of patients who all have the same condition—be it cancer, asthma, diabetes, or something else—that the drug is aimed to treat, and can last from a few months to a couple of years.

Many Phase II studies are performed using random selection, known as "randomized", where one group of participants receives the experimental drug and a second group will get standard treatment or placebo. The main goals of Phase II trials are to produce the intended result of the drug and track any side effects. During this phase, participants will get identical dosages of the medication; however, some participants will be placed in groups where the drug will be given differently. There is also the possibility that different dosages will be given to some participants to try and find the best combination of safety and overall effectiveness. Despite the increased size, it is not large enough to prove whether or not the drug will be beneficial for the condition it is targeting. Once Phase II studies are complete, it is determined whether the drug will move to a Phase III study. The FDA claims that roughly 30% of all tested medications make it through Phase II.

Phase III

Once a drug passes through the Phase II study, aspects of the trial begin to scale up as the drug gets closer to general consumption with a Phase III clinical trial. Phase III trials involve randomization and blind (not knowing whether a patient is getting a placebo or the experimental drug) studies. They can last anywhere from one to four years and involve upwards of 3,000 participants from around the United States that have the disease or conditions being targeted.

At this stage, it still has not been determined if the medicine being studied is better than what is currently available to patients. Some participants will receive standard treatment for the condition, while others will receive the new drug to compare and contrast the effectiveness and side effects. Another key point of Phase III clinical trials is that they will provide the most data and information for doctors.

Because of the increased number of patients receiving the drug, new, less common side effects may arise. Of the drugs that make it to Phase III, about 25% of them move on to Phase IV.

Phase IV

The final phase—Phase IV clinical trials—happens when the FDA needs more information on the drug that is being studied. Phase IV studies are commonly referred to as Post-Marketing Surveillance Trials.

At this point, the drug has already been submitted and approved by the FDA for consumer sales, but there may be important questions that remain unanswered. These questions can include long-term safety, cost-effectiveness, or if there are any other potential benefits of taking the medication. These trials will usually involve thousands of people because the medication is readily available for doctors to prescribe to patients. Patients who are not enrolled in the study can have access to the treatment, as doctors can prescribe it. However, they are made aware of the state of the medication if it is still being tested at the time of the prescription.

Depending on the outcome of the Phase IV study, a medication that was previously approved by the FDA could see usage restrictions put in place. There is also the possibility of the drug being removed from the market altogether.

In the End

Due to the unknown nature of medical discoveries, clinical trials, and the various phases, are some of the most important aspects of patient care. Thanks to the people who volunteer to participate in a clinical trial, many people can benefit from the research for years to come and can find the best treatment option for them. 

Learn more about clinical research and trial participation in our Clinical Trials 101.