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Many people wonder what it is like to participate in a clinical trial. Some have never been introduced to the concept of a clinical research study, and do not have a good understanding of the requirements of participation. Others may be more familiar with clinical studies, but simply want to learn more. The key questions that people ask themselves before participating in a clinical trial is “what is this,” and “is it right for me?”
There are many factors to weigh when considering participation in a clinical trial. Your decision to join is likely to be based upon several factors, such as the clinical development phase of the drug under study, protocol requirements (i.e., what you must “do” as part of the trial), the risks and benefits of participation, and your understanding of your rights as a human subject. You also may want to know if you will receive an active treatment for a medical disorder, if you have the chance of receiving placebo (sugar pill), or if you will be paid for your time. Whatever is the case, if you do decide to volunteer for a clinical research project you will be among the many volunteers each year who help pharmaceutical and biotechnology companies bring new drugs to those in need. We consider these people to be “medical heroes.”
So, what are clinical trials? Clinical trials are research studies that involve the testing of new investigational drugs or medical devices. Such trials are done in order to evaluate new drugs that have not yet been approved or are pending approval by the US Food and Drug Administration (FDA). Trials also may be done to test a new drug against approved medications, in new patient populations or new forms, or in other circumstances.
Clinical trials are conducted in three different phases prior to a drug’s approval. One additional phase (Phase IV) includes studies conducted after marketing approval. Trials performed during the first of these phases of clinical development provide important information that constitutes the manufacturer’s evidence for carrying a drug forward, and form the fundamental basis of the NDA that is submitted to the FDA. It is important to note that although these phases are numbered and represented in consecutive order, it is common for studies to overlap or even run concurrently. For example, a Phase II study of a drug may be in progress when an important Phase I drug-drug interaction stdy is initiated.
In Phase I studies, researchers test an investigational drug or device in a small group of people (20-100), usually normal healthy volunteers, but in certain circumstances patients with health problems also will be tested. These studies are designed to determine the basic characteristics of a drug and how it is absorbed by the human body, how it is broken down, and how it is digested or eliminated from the body. These studies always follow extensive pre-clinical tests in animals that give researchers an idea of the proper amounts of medication that should be tested. Most importantly, Phase I studies offer us an opportunity to learn about the types of adverse experiences or “side effects” that might be associated with a new medication. This is one way that scientists can document that a drug is safe, and appropriate for further testing.
During Phase II, an investigational drug or device is given to a larger group of people (100 – 500) in order to evaluate the effectiveness of a drug for a particular indication or indications in patients with the disease or condition under study. Phase II studies also aim to further document the common short-term side effects and risks associated with the drug or device under evaluation. In clinical trials, it is common for Phase II studies to identify outcomes that will later be used in larger “pivotal” trials done later in development. For example, when testing a new drug under development for the treatment of cancer, scientists have to make a decision, up front, about the outcome they will look at to determine if a drug is effective. Is it the number of cancer cells, is it the size of a tumor, or is it some other measure? Most importantly, Phase II offers drug manufacturers an opportunity to determine the drug dose or doses that it will carry forward into the next phase of development by weighing the trade-offs between increasing effectiveness and the risk of side effects.
Phase III “pivotal” studies represent the drug manufacturer’s most important opportunity to document the effectiveness and safety of their drug products by testing them in large groups of people (1,000 – 5,000). Studies conducted during Phase III are intended to gather critical information regarding the overall benefit-risk relationship of a drug, as well as provide an adequate basis for labeling. The label is also known as the “package insert” and these are the instructions that doctors, pharmacists, and patients get about the proper use of a medication. By the time a drug enters this phase of testing, its basic characteristics are well-known, its likely therapeutic effects have been defined, and its safety profile has been reasonably characterized. Manufacturers who initiate Phase III trials generally are confident that their product will be shown to be safe and effective, and ultimately will win regulatory approval. Even though the odds of success are much higher for a drug product at this point than when entering pre-clinical evaluations, only one out of every five drugs that enters Phase II testing will successfully complete Phase III and become a marketed product.
After a drug’s NDA has been approved by the FDA, Phase IV trials may be conducted to further clarify its efficacy and safety. New and specific patient populations are likely to be studied. For example, a drug may be tested in the elderly or in children to determine its therapeutic benefits in these so-called “special” populations.
There are occasions when Phase IV trials provide information that is used to revise the labeling of a drug product (e.g., the inclusion of additional adverse event information), and some Phase IV trials may support a manufacturer’s decision to pursue a secondary NDA (sNDA) that seeks approval for a new therapeutic indication for a drug.
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