Guest Author: Amber Trzeciak, Cadent Therapeutics
Clinical trial phases can be a confusing concept to understand. The purpose of clinical trials is to determine how a drug or device (intervention) will interact with a human being. Trials are regulated by our governmental agency the FDA (US Food and Drug Administration). They set forth many guidelines and rules that sponsors (those testing the intervention) must follow before administering their drug or device into human volunteers. Before getting into clinical trial phases, first we will address how a drug or device gets to the point of being approved for administration to humans.
Non-Clinical Development Phases
Every intervention idea begins in a laboratory. This is where researchers begin to develop and discover products or compounds that will help stop or reverse the effects of a disease or condition. From this development phase, the device or compound moves into preclinical research. Here researchers will test their device or compound in vitro, which is in cells in dishes or vials, or in vivo, which is in living animals (rodents, dogs, monkeys, etc). The purpose of preclinical work focuses heavily on determining the amount of drug or device that is considered safe and not toxic.
Once the researchers determine that they have a device or drug compound that they think will work they submit an application to the FDA. This application is called an Investigational New Drug (IND) and it lays out the specifics of what a drug developer (sponsor) hopes that their device or compound will accomplish. The application also includes details of all the current research on this device or compound, including the demonstrated safety and tolerability of it. Most importantly, it includes a protocol. A protocol is a study design plan that maps out what the clinical trial will look like. For example, the protocol will provide information on duration of the trial, who can and cannot participate in the trial, how the device or drug will be administered, and any assessments to be included (for example, blood draws). If the IND is approved by the FDA, the sponsor can move into starting their clinical research.
Clinical Development Phases
Clinical research starts when a drug compound or device is granted access to begin its clinical trial phases. Clinical trials can have any where from 0-4 phases, with phases 1, 2, and 3 being the most common.
Phase 1 Clinical Trial
Most sponsors start with a Phase 1 clinical trial. A Phase 1 trial most often uses healthy volunteers who do not have the disease or condition in which the drug or device may treat. A Phase 1 trial checks for safety and tolerability of the drug, or more simply how the drug affects the body and how it should be given (for example, tablet versus capsule). Most importantly, a Phase 1 trial monitors for any potential side effects. If a Phase 1 trial is determined to be successful it moves onto the next trial phase, Phase 2.
Phase 0 Clinical Trial
At times, there may be mention of a Phase 0 clinical trial, this is less common, but often involves very small amounts of volunteers who have the disease or condition that is hoping to be treated. Often these volunteers participate for a much shorter time and are given a smaller dose of the drug compound. The purpose of a Phase 0 trial is to help expedite moving on through the other phases, or more simply put, weeding out the bad compounds early on without wasting time and resources.
Phase 2 Clinical Trial
A Phase 2 clinical trial involves actual patients who are impacted by the disease or condition that the drug compound or device is hoping to target. The intent of a Phase 2 trial is to test the “efficacy”, which is whether the drug does what the researchers intended, and if it causes any side effects. The volunteer population is usually larger than the first phase trial and the duration can vary depending on the sponsor’s needs. There are different options available for a Phase 2 trial that can include what is called “open-label” or “placebo-controlled”. The difference is that if a trial is open label, everyone in that trial receives the actual drug, versus a placebo-controlled trial that offers some volunteers a placebo intervention (non-drug) whereas some volunteers are given the actual drug. If this route is chosen, a sponsor can also determine to make the trial blinded (no one knows who receives actual drug or placebo) or unblinded (the sponsor knows who received the actual drug versus the placebo intervention). The take-away for going with a blinded study is that your results will more likely be accurate due to the elimination of any bias. If the Phase 2 trial is determined to be successful, it is approved to move onto the next trial phase, Phase 3.
Phase 3 Clinical Trial
The purpose of a Phase 3 clinical trial is to determine if a drug or device offers treatment for a specific disease or condition within a widespread population safely. The main information gained from a Phase 3 is most importantly, safety data, which determines if there any long-term side effects. Typically, this trial phase includes the largest number of participants and lasts the longest. To be considered successful in this phase, the drug or device must be considered safe and prove to be more effective or as effective as other treatments available.
Once a Phase 3 trial begins to wrap up and show positive data, the sponsor seeks approval of this drug or device from the FDA. If the drug or device is filling an unmet need, the team can request to be fast tracked by the FDA which allows for priority review from the FDA. This means that the FDA must review the data and information within 6 months of receiving the application. Another benefit to being considered fast track by the FDA is that the drug or device can be eligible for accelerated approval. The FDA can then grant authorization of this drug or device based upon evidence presented. These designations are only for drugs or devices that provide a new or better treatment option for a disease or condition.
Phase 4 Clinical Trial
A Phase 4 clinical trial occurs after a drug or device has been approved by the FDA and can be used by patients. It continues to monitor the safety and efficacy of that intervention, in real time. This trial occurs without the conditions of being conducted in a research facility and can provide feedback on details that may have not otherwise been noticed.
Why is it important to participate in a clinical trial?
Without volunteers, many medications and devices would not be where they are today. We thank you for your participation!
How to find clinical trials that may be relevant to you:
First and foremost, the FDA has created an online portal where you can search for clinical trials by disease, condition, location, phase and by sponsor.
Another alternative is to use the Pipeline page, found on most sponsor’s websites, for example:
These pipelines provide a quick snapshot of where the company is in the process of the clinical trial phases for their specific disease or condition.
Resources: FDA (https://www.fda.gov/patients/learn-about-drug-and-device-approvals)
About the Author
Cadent Therapeutics, Inc.
Patient Partnership and Advocacy Manager
Amber Trzeciak is the Patient Partnership and Advocacy Manager for Cadent Therapeutics in Cambridge, Massachusetts. She joined the small biotech company in 2017. Originally from Pittsburgh, PA, Amber transitioned to the Alexandria, VA area during her 10 plus years as a Mental Health Counselor. Amber brings nearly 20 years of advocacy experience to her work within the biotechnology field. She has a passion for helping others and often finds herself rallying friends, family, and colleagues to help at events that she supports.
Amber has a M.S. in Clinical Mental Health Counseling from Indiana University of Pennsylvania, a M.S. in Legal Studies-Law and Public Policy Concentration from California University of Pennsylvania and her bachelor’s degree is in Criminology, also from Indiana University of Pennsylvania.