Clinical trials: What are the 4 phases of clinical trials and why enroll?

What are the 4 phases of clinical trials?

Clinical trials are comprehensive studies undertaken in 4 main phases involving human volunteers, after a new drug goes through preclinical studies in laboratory and/or animal tests. Generally, later-phase trials collect greater amounts of data from larger populations, and by that point a decent amount of safety information has been formally collected on the study drug. Earlier-phase studies are more exploratory in nature, aiming to gather data about the drug in its first uses in human subjects. Not all drugs make it to phase IV. Certain aspects of the different clinical trial phases may overlap (for example, they all collect safety information), but there are prominent differences which we will discuss below in hopes that it helps you understand the information you come across and be able to find a clinical trial that is right for you.

Phase I clinical trials - also known as dose-escalation studies, are designed to identify the best method of administration and the maximum tolerable dosage (MTD; the maximum dose that doesn’t cause unmanageable side effects), in 20-100 volunteers (typically healthy individuals). Since little is known about the safety of the drug at this point, these can be considered higher-risk trials, as a generalization.
Phase II clinical trials - also known as dose-finding studies, are designed to test the new treatment/drug in a larger population (around 100-300 participants) and determine the most successful dose (MSD; the dose with the best ratio of benefit to side effects).
Phase III clinical trials - also known as pivotal studies, involve monitoring the drug’s side effects in somewhere around a hundred to a thousand participants. By this point, there is a fairly good amount of safety data on the novel drug. These are considered the “bulk” of clinical research studies, providing the most robust evidence for efficacy and safety in a larger population, and often lasting multiple years. If results are favorable, a New Drug Application (NDA) is filed with the FDA and the drug is approved for use.
Phase IV clinical trials - also known as post-marketing surveillance studies, involve long-term safety monitoring of the drug under real-world conditions. These may often be observational studies, meaning that patients taking the drug to control the condition are simply monitored and there is no direct intervention by researchers unless issues with safety, tolerability, or efficacy are identified.

Why enroll in a clinical trial? What are the potential benefits?

As of November 2022, there were around 228,000 registered clinical studies outside of the U.S., and over 136 thousand in the U.S. alone. Volunteer participants are required for each and every one of these studies in order to bring about measurable results, so there is no shortage of opportunity for participation. Clinical trials represent a vital aspect of healthcare research, yet they cannot guarantee personally positive outcomes for all participants. So, why would you enroll in a clinical trial?

One of the major benefits of enrolling in a clinical trial is that you may get access to a novel treatment for your condition well before they are available to the public, and often for free or at an extremely reduced cost. This could be a strong motivator if you have not responded well to currently available treatments, or if there aren’t any available at all. Another motivation is taking an active role in your health and healthcare decisions. Beyond the personal level, participating in clinical research represents a significant contribution to healthcare and advances in treatments which may help many other people, both current and future. Thus, there is a strong aspect of “making a difference” that may motivate some volunteers. There are also many trials enrolling healthy volunteers, and researchers urge healthy individuals to find a clinical trial and contribute to the advancement of science and healthcare as well. Still other trials offer monetary compensation for participation, although this should not be the main reason for taking part in a clinical trial as there are arguably much more important factors at play.

Paid clinical trials

One of the questions potential participants may ask is "are clinical trials free?” This is a reasonable question, as it is important to understand potential financial costs of participation and what is and is not covered by the study sponsor and your insurance provider. Generally, treatments and tests directly required by the study protocol are paid for by the trial’s sponsor. This includes the new treatment/drug being tested and costs related to check-ups and other medical interventions that are part of the study. Other aspects may not be covered, for example routine tests or treatments that are not related to the clinical trial. It is important to consult with your insurance provider and the study investigators to clarify who covers what costs before enrolling. It is also important to consider potential expenses related to travel, time off work, childcare, which are less likely to be covered.

Nonetheless, some paid clinical trials offer monetary compensation to their volunteers for participation or travel expenditures. That being said, monetary gain is not the correct reason to enroll in a clinical trial. Be sure you are aware of what participation requires of you, the potential risks, and possible out-of-pocket expenses that would be your responsibility to cover.