Despite thousands of molecules being evaluated as potential medications every year, only 53 medications reached FDA approval in 2020. Believe it or not, 53 is actually a record high!
New medical treatments have to undergo rigorous testing to prove their efficacy and safety in humans. The different clinical trial phases walk the medication through testing, slowly expanding to larger and larger groups of participants until the medication is deemed successful. The phases are very well structured and are fascinating to learn about.
If you want to learn how your medication gets developed, keep reading for all you need to know about the different phases of clinical trials.
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Phase I clinical trials are typically the first testing done on humans for the drug. The primary focus of Phase I is evaluating safety.
Though we have a concept of how the drug will work from preclinical testing, it is not always a seamless transition to the human body. The way one molecule may be metabolized in an animal does not guarantee that it will be metabolized the same way in the human body.
Studies at this phase contain very few participants, usually fewer than 10. There is no placebo group at this stage as the investigators will be very closely observing the participants to monitor for any side effects.
Phase I clinical trials also help start to lay out an acceptable dose range in humans. Investigators at this stage will want to understand what the maximum tolerable dose will be in human subjects.
Phase II clinical trials explore the drug’s efficacy. Investigators want to see whether or not the dose will have the intended effect.
At this stage, we start bringing in more subjects. Phase II clinical trials can range from about 25-100 subjects, usually spread out across multiple sites.
Phase II clinical trials also serve as the beginning of control groups. Different treatment groups can compare different dosages of the drug and can compare the medication effectiveness of the investigational product against a placebo (a fake medication that has no treatment impact on the human body).
The placebo effect is strong. By directly comparing the study medication to a placebo, we can ensure that the medication is truly more effective than a placebo. To ensure neither the research staff nor the subjects know which medication the subjects receive, these types of studies maintain a double-blind.
This stage also helps us narrow our dosing range. By directly comparing one dose to another, we can evaluate the safety and efficacy of the medication.
Because there are more subjects in Phase II, we are also able to recognize side effect trends. In Phase I, there are so few subjects it is difficult to determine whether or not reported adverse events are associated with the investigational product or are coincidental. With more subjects enrolled, researchers are able to identify trends and start to establish their relationship to the product.
If there is a significant number of serious adverse events (called SAEs), the trial may not proceed to Phase III. Additionally, if the drug is not shown to be effective it will not proceed. Around 1/3 of drugs pass Phase II and enter Phase III.
Phase III trials are when we begin to drastically expand the study. These trials usually contain hundreds to thousands of subjects and are conducted at sites across the country and often in countries around the world.
The goal of a Phase III trial is to establish if the investigational product is better than what is already FDA-approved and on the market. These trials are typically double-blind, with treatment groups of the new medication, currently-available medication, and/or placebo. Directly comparing these groups can show us whether or not the medication is truly more effective than the current standard of care.
Phase III trials are massive operations. There are hundreds of personnel involved in these trials at every level:
- The Principal Investigator (the doctor at your treatment site)
- Clinical Research Coordinators (the staff who handles day-to-day research operations at sites)
- Monitoring staff (independent research professionals who ensure the site is conducting the study properly)
- Pharmaceutical companies (Sponsors, the maker of the drug in the trial)
- Site management organizations (SMOs)
- Independent Review Boards (IRBs)
- Clinical Trials Supply distributors
And more! All of these people work together in harmony to ensure the study is safe.
If the medication is shown to be effective and safe at this stage, it is ready to submit to the FDA for approval. If the FDA approves the investigational product, it will be available for sale in the United States.
Phase IV trials help us monitor the medication after it is approved. Though Phase III trials are relatively longer than earlier stages, they usually do not extend beyond a few years. We still want to observe the drug and its safety and efficacy in the long term.
In the previous stages, we should have established that the drug is safe and effective. But are there long-term side effects we should know about? Does the medication maintain its level of effectiveness after numerous years of use?
Answering those questions involves the largest population of subjects. There are often thousands of subjects enrolled in these trials. The trials are somewhat less involved for subjects, as the medication should fit into their standard of care routines.
These are also the safest trials for subjects, as the drug has passed many rounds of testing with many subjects.
Exploring the Wonderful World of Clinical Trial Phases
Clinical research is constantly growing and evolving. New medications are constantly being developed for all types of diseases and conditions, all of which need to be tested for safety and efficiency. These established clinical trial phases help guide a new drug through the process of testing in a way that is safe and efficient.
It really is an amazing process! For more amazing information about all things lifestyle, check out the rest of the blog!