Background

A clinical trial is a research study aimed at answering specific questions about vaccines, new therapies or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people.

Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the treatments with the most promising laboratory results are moved into clinical trials. Clinical trials are conventionally classified into different phases. During a trial, more and more information is gained about a new treatment, its risks and how well it may work or not.

A regulatory authority, such as the Food and Drug Administration (FDA) in the United States or the European Agency for the Evaluation of Medicinal Products (EMEA) in Europe, must approve a substance as a drug before it can be marketed. The approval process involves several steps including pre-clinical laboratory and animal studies, clinical trials for safety and efficacy, filing of a New Drug Application by the manufacturer of the drug, authority review of the application, and authority approval/rejection of application.

Phase definitions

Clinical trials are categorized as Phase I to IV trials. Chiesi Group defines the Phase I to IV clinical trials as follows:

Phase I (small number of healthy volunteers; in certain cases, i.e. virology/oncology, also patients).
Phase I studies are designed to allow scientists and medical doctors to understand what effects an investigational compound has in human subjects. The goal is to study what happens to the investigational compound in the body from the time it is swallowed or injected until it is excreted, when it is excreted and how the human body reacts to the new compound from a safety and tolerability point of view. Study participants are monitored for the occurrence and severity of any side effects that they may experience.

Phase II
Phase II studies are designed to evaluate the safety and efficacy of an investigational compound in patients with a specific disease or condition. Phase II trials are typically conducted in a group of patients who are usually selected based upon being at the same stage of a disease. The patients are given various doses of the compound and closely monitored to compare the effects and to determine the safest dosing regimen. In many instances, multiple Phase II studies are conducted to test the compound in a variety of patient populations or indications.

Phase III
Phase III studies are designed to confirm the safety and efficacy of an investigational compound and the dosage regimen chosen in large numbers of patients with a specific disease or condition. These studies, like the previous ones, may involve one or more ‘treatment arms’, which allow the investigational drug to be compared to other available treatments, or to be tested for effectiveness in combination with other therapies. The safety and efficacy of the new compound is compared to that of the currently accepted standard treatment. Information obtained from Phase III studies is used to determine how the compound is best prescribed to patients in the future. The complete information available on the new compound is submitted to Health Authorities.

Phase IV
Phase IV studies take place after the drug has been approved for marketing and are designed to provide broader experience in evaluating the safety and effectiveness of the new medicine in larger numbers of patients, subpopulations of patients, and to compare and/or combine it with other available treatments. These studies are designed to evaluate the long-term effects of the drug. Under these circumstances, less common adverse events may be detected.