Mike Straw - Nov 20, 2018

Clinical Trials Consist of Four Phases: What are they?

Clinical trials is a term that many people have heard, but not enough seem to know about.

Conducted to collect data about the efficiency and safety of a potential new treatment option, clinical trials are multi-level processes that involve numerous steps, or phases in this case. The information gathered helps researchers and doctors make sure everything is up to the required standards before a drug ever sees the light of day for public utilization.

For the longest time, trials consisted of four main phases, but before getting into more detail about those and what each represents and 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 aren’t 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.

With this phase, the likelihood of any volunteer seeing a benefit of taking part is slim-to-none simply because of the small dosage being 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 in order to determine if the testing should continue. After each phase, an investigator is required to submit all findings to the FDA for review and approval.

At this point, you’ve 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. It is also where testing is done to actually see how the human body reacts to the experimental drug.

Participants will include small -- typically a couple dozen -- number of people. In some cases, patients can suffer from different cancers or ailments and still take part in the same Phase I study.

With 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 orally, subcutaneously 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 in order 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 duration of the study as new patients are added until the desired effect of the drug is documented, or the side effects become too severe for the participants.

Usually administered in major cancer centers across the country, Phase I trials do not involve any placebo and are done to find out what the drug will do to the body.

Because of the truly unknown nature of how the drug interacts with the human body, 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 of testing pass.

Phase II

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

Many Phase II studies are randomized trials where one group of participants receive the experimental drug while a second group will get standard treatment or placebo.

The major goal of Phase II trials is to produce the intended result of the drug, as well as track the side effects in patients. During this phase, patients will get identical dosage of the medication though some will be placed in different groups where the drug will be given in a different way. Further, there’s the possibility that different dosages will be given to some participants in order to try and find the best combination of safety and overall effectiveness. Despite the increased size, however, it is not large enough to prove whether or not the drug will be beneficial for the disease it’s targeting.

After Phase II studies complete, it’s determined whether or not the drug will move to a Phase III study. The FDA claims that about one-third of all tested medications make it through Phase II.

Phase III

Once a drug passes through the Phase II study, things begin to scale in a larger fashion as it works closer to general consumption with a Phase III clinical trial.

Continuing with the randomization and blind (not knowing whether a patient is getting a placebo or the experimental drug) testing, Phase III studies last anywhere from one to four years and involve upwards of 3,000 patients from around the United States that suffer from the disease or conditions being targeted.

At this stage it still hasn’t been determined if the experimental medicine is better than what is currently available to patients. Due to that fact, some patients will receive a standard treatment for the condition while others will receive the new drug in order to compare and contrast the effectiveness and side effects. Another key point of a Phase III clinical trial is that it will provide the most safety data for doctors.

Because of the increased number of patients receiving the drug, it’s possible that new, less common side effects arise. Long-term side effects are even likely to appear due to the length of the trial itself.

Of the drugs to make it to Phase III, about a quarter of them move on to Phase IV.

Phase IV

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

At this point, a drug has already been submitted and approved by the FDA for consumer sales, but there may be important questions that remain unanswered like long-term safety, cost effectiveness, or if there are any other potential benefits from taking the medication.

These trials will usually involve thousands of people because the medication is readily available for doctors to prescribe to patients. Because of a doctor’s ability to prescribe the medication, patients who aren’t enrolled in the study can have access to the drugs. However, they are made aware of the state of the medication if it is still being tested at the time of a script being written.

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

In the End

With the unknown nature of when new medicine will be discovered, clinical trials and the various phases are some of, if not the most important aspects of patient care. Thanks to the willingness of the participants, many people who don’t even know it yet will benefit from the research being done to find the best treatment options for their ailment.

Written by Mike Straw

Mike Straw is the lead developer at TrialScout. With the visitor in mind, Mike's primary focus is to make sure TrialScout is not only easy on the eyes but easy to use for everyone. In addition to development, he helps create content and graphics for TrialScout. Mike is also is a veteran journalist who has been lucky enough to travel across the United States and Canada while having his work appear on major outlets such as Yahoo! and Sports Illustrated. When not focusing on his work, Mike spends his free time honing his craft as a guitarist while writing his own music.

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