After countless hours of dedicated lab work from a team of scientists, they finally see the results they were hoping for and believe they have found a new drug or treatment. Before this newly discovered drug or treatment can be approved by the FDA for public use, the scientists must fill out a Pre-Investigational New Drug application. This application, if approved by the FDA, grants access to use the drug in trials on humans. Once they gain approval the treatment must then go through a rigorous clinical trial process to test for safety and efficacy. The clinical trial process consists of four phases that look at different aspects of the drug and its effects on people. Each phase plays a key role in determining if the potential treatment is a viable option for people with the disease or condition it is designed for.
The initial phase in the clinical trial process is designed to test the safety of the potential treatment and find the correct dosage for administration. This phase is small in scale and typically consists of 20 to 80 healthy and usually compensated volunteers. In some cases people with the disease or condition the drug is designed for will also participate. The researchers use this phase to observe how the drug or treatment interacts with the human body. The dosage is adjusted to determine how much a person can safely tolerate and what the side effects are. Calculating how much the body can safely tolerate will give clinicians the optimal dosage to use in the later phases. Some early evidence of the effectiveness of a drug may be observed during this phase. Phase I lasts several months and, according to the FDA, approximately 70 percent of drugs move from Phase I into Phase II. Determining the correct dosage and reviewing the side effects help set up the design of the Phase II study.
In Phase II researchers administer the treatment to people living with the disease or condition it was designed for. It involves up to several hundred participants and provides more information about the safety and efficacy of the drug or treatment. During this phase researchers are trying to see if the treatment can prove to be efficacious. Many Phase II trials involve a randomized experiment where one group of the participants receives the experimental drug while the other group, the control, receives a placebo. These trials are also typically “blind studies” which means that neither the participant nor the researchers know who received which. Although the number of participants is expanded compared to Phase I, it is still not large enough to determine definitively if the drug is an effective treatment for the disease or condition. This phase lasts anywhere from several months to several years and the FDA estimates that about 33 percent of all new drugs move on to Phase III.
Also known as pivotal studies, Phase III involves several hundred to several thousand participants and takes several years to complete. The goal of a Phase III trial is to determine whether or not the drug will provide an improved treatment when compared to already available options. This phase also contributes to much of the safety data that researchers gather during the clinical trial process. Due to its expanded participant size and increased study length, rare or long term side effects that may not have appeared or been noticed in the first two phases may become more evident. The FDA estimates that approximately 25 to 30 percent of all drugs move past Phase III. After completing this phase, application for approval of the potential treatment can be sent for review by the FDA.
Also known as Post Market Safety Monitoring, Phase IV occurs after a drug has been approved by the FDA. Phase IV involves thousands of participants who have the disease or condition that the drug was designed for, and can last several years. Even after all the testing that takes place in phases I through III, researchers may not have all the information about the long-term safety or efficacy of a drug. This phase allows researchers to observe the long-term effectiveness of the drug, the extent to which it increases the quality of life for people with the disease or condition it was designed for, as well as any long-term side effects that may not have been noticed during previous phases. There are some exceptions to this phase. For example, drugs for orphan diseases, those that affect less than 200,000 people nationwide (which includes ALS), may have an accelerated Phase IV process.
Developing a new drug and bringing it all the way through the clinical trial process is a long and difficult task. It is designed to guarantee that potential drugs and treatments are both safe for use and effective at treating the disease or condition they were designed for. The four different phases each play a vital role in ensuring that only safe and efficacious drugs and treatments are made available on the market. Even though that is the typical process new drugs go through there are some exceptions to this pattern. Orphan diseases, those that affect less than 200,000 people nationwide like ALS, may have an accelerated track to being approved. Due to the nature of these orphan diseases there is typically no effective treatment available in the general market. Because of this developers may apply for fast track, accelerated approval or priority review status to help speed the process along while still testing the safety and efficacy thoroughly. Despite these exceptions to speed the process up, it is still a time consuming and difficult task that can be frustrating for researchers and potential patients alike. It is easy to understand why it is frustrating but it’s also important to remember that this process was designed to ensure the safety of people who will use the drug and conducting and reviewing the data of the studies takes time. To learn more about currently enrolling clinical trials for people living with ALS, click here.