Clinical trials are required to demonstrate how new drugs or therapies, medical devices, and surgical techniques impact human participants. 

Clinical trials are typically carried out in three to four distinct phases. Each phase plays an important part, helping investigators to answer important questions related to the therapy’s safety, side effects, efficacy or ability to meet its desired clinical endpoint, and more. 

The four phases of clinical trials

Phase I: The initial phase of a clinical trial is often referred to as the first-in-human trial. This phase involves a small number — typically in the tens — of patients. Phase I drug trials usually move very slowly, enrolling about three participants at a time and then monitoring those participants closely for a number of weeks before sponsors and investigators deem it safe to enroll more. 

Typically, to start, there are pre-determined dose levels, predicted from animal or pre-clinical studies. The first group of about three participants that is enrolled receives the lowest dose of the drug, or dose level 1. Each subsequent group that is enrolled receives an increased dose (dose level 2, dose level 3, and so on), assuming that the dose before it was deemed safe. Phase I trials allow the trial investigators to evaluate how human participants respond to the drug, how the drugs are metabolized, and what doses are safe. This initial phase provides important insight into the safety and tolerability of the new drug or device, and this information helps guide the design of Phase II trials.

Phase II: After initial safety data has been collected in the Phase I trial, a larger study is conducted and typically involves 100 to 300 patients, depending on the disease. The purpose of Phase II trials is to collect more safety information, specifically side effects, to explore the clinical impact of different dosages or dosing schedules, and to start to look at efficacy — or if the drug or device has any effect on the disease or condition being studied. This often involves running parallel trials concurrently, so that the impact of the therapy or device can be studied in different patient subpopulations or for different clinical indications. 

Phase III: This phase involves enrolling a larger group of patients, typically 1,000 to 3,000 participants depending on the disease, in which participants are often randomized, or randomly assigned, to one of two or more trial arms. An arm can be a new drug or combination therapy, the standard drug or combination therapy, a new drug in combination with a standard drug, or no therapy (usually a placebo or observation group) if no standard treatment currently exists. The purpose of Phase III trials is to evaluate the efficacy of the new drug or device compared to the current standard treatment for that disease or condition, and continue to collect safety and side effect information. Most often, an application for approval is submitted to the FDA after the completion of a Phase III trial if the data collected for the new drug or device shows that its efficacy is as good or better than the current standard treatment and it has an acceptable safety and side effect profile.

Phase IV: While the data collected during Phase I, II, and III trials are submitted in an application to seek approval by the FDA (and other global regulatory bodies), Phase IV trials are carried out to study the drug or device once it has received regulatory approval and is being prescribed to patients in real-world clinical settings. 

Often referred to as post-marketing studies, Phase IV trials aim to study the safety and efficacy of a new drug or device over longer periods of time in real-world populations of patients — groups that will typically be more diverse than the similarly grouped human subjects that are included in Phases I, II, and III trials.

Phase IV studies are essential to broaden the medical community’s understanding of how the drug or device works when prescribed to patients who may have different age demographics or underlying conditions compared to those patients enrolled in the initial trials. Phase IV studies also aim to study longer-term clinical and safety impacts of the drug or device in actual prescribing scenarios. 

This blog is intended to be informational in nature. The information and other content provided in this blog, or in any linked materials, are not intended and should not be construed as medical advice, nor is the information a substitute for professional medical expertise or treatment.

If you have any questions or concerns, please talk to your doctor. Never disregard professional medical advice or delay in seeking it because of something you have read on this blog or in any linked materials. If you think you may have a medical emergency, call your doctor or emergency services immediately.

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