Clinical trials 101

A clinical trial is a specific type of medical research in which humans are studied to see how they respond to promising new treatments, including drugs, therapies, devices, and procedures. Clinical trials often lead to treatments or even cures that are safer, more effective, and have fewer side effects. The clinical trial process is regulated by the U.S. Food and Drug Administration (FDA), which is responsible for authorizing new treatments to enter the health care market.

Finding better ways

Health researchers are always looking for better ways to identify, diagnose, treat, manage, and prevent medical conditions. Whether publicly or privately funded, research often begins with pre-clinical testing, meaning tests done in a laboratory without human participants.

When researchers find a possible treatment, they first test it in computer models, bacterial cultures, and/or on isolated human cells. If the treatment seems to work, the testing usually advances to animals, to learn how it affects them and how it might affect humans. Pre-clinical testing may span months or years.

The treatments that make it to clinical trials already have shown promise and a reasonable risk-to-benefit ratio. The standards for entering a clinical trial are so strict that only about five in 5,000 new treatments that begin the road toward clinical trials are approved by the FDA for human testing.

Once a treatment is optimized in the laboratory, a public or private entity (called a sponsor) may apply for an Investigational New Drug (IND) application with the FDA. The FDA decides whether it is reasonably safe for the sponsor to move forward with testing the treatment in humans. The clinical trial process usually takes several more years.

By the time a clinical trial is offered as a beneficial treatment option to patients, its potential is clear, and it has been determined to be relatively safe. The plan for a clinical trial must gain approval from the FDA and be overseen by an institutional review board (IRB), a panel of scientists and non-scientists at research institutions such as UAB Medicine.

The four phases

Clinical trials advance through three phases to test a treatment, find the appropriate dosage, and look for side effects. After the first three phases, if researchers find a treatment to be safe and effective, the FDA approves it for patient use and continues to monitor its effects in a fourth phase.

• A phase 1 trial tests an experimental treatment on a small group of people (usually numbering 20-80) to judge its safety and side effects and determine the correct dosage.
• A phase 2 trial involves more people (100-300). While the emphasis in phase 1 is on safety, the emphasis in phase 2 is on effectiveness. This phase seeks to obtain data on whether the treatment works in people who have a certain disease or condition. These trials also continue to study safety, including short-term side effects.
• A phase 3 trial gathers more information about safety and effectiveness, studying different populations and different dosages and combining the treatment with other drugs. The number of participants usually ranges from several hundred to about 3,000. If the FDA agrees that the trial results are positive, it will approve the experimental drug or device.
• A phase 4 trial takes place after the FDA approves the treatment or device and is done to monitor for longer-term effects.