Clinical trials
Pharmaceutical clinical trials are commonly classified into four phases, and the drug-development process will normally proceed through all four stages over many years. If the drug successfully passes through the Phases I, II, and III, it will usually be approved for use in the general population. Before clinical trials on drugs start, extensive pre-clinical studies are conducted.
Phase I - Phase I trials are the first-stage of testing in human subjects. Normally a small group of healthy volunteers will be selected (20 – 80 people). This phase includes trials designed to assess the safety tolerability, and mode of action of a therapy. These trials are almost always conducted in hospital, where full-time medical staff can observe the subject. The subject is usually observed until the medical staff can be certain that the entire trial drug has been excreted from the body. Phase I trials also normally include dose-ranging studies so that doses for clinical use can be refined. The tested range of doses will usually be a small fraction of the dose that causes harm in animal testing. Phase I trials most often include healthy volunteers, however there are some circumstances when patients are used, such as with oncology (cancer) and HIV drug trials.
Phase II - Once the initial safety of the therapy has been confirmed in Phase I trials, Phase II trials are performed on larger groups of people (20 - 300) and are designed to assess clinical efficacy of the therapy; as well as to continue Phase I assessments in a larger group of volunteers and patients. If a new drug fails during its development process it most commonly fails during Phase II trials. Failure is normally due to the discovery of poor efficacy or intolerable side-effects.
Phase III - Phase III studies are randomised controlled trials on large patient groups (300–3,000 or more depending upon the condition) and are aimed at being the definitive assessment of the efficacy of the new therapy, in comparison with current 'Gold Standard' treatment. Phase III trials are the most expensive, time-consuming and difficult trials to design and run; especially in therapies for chronic conditions. Once a drug has proven satisfactory over Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life.
Phase IV - Phase IV trial is also known as Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (for example, the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses: recent examples involve drugs like Lipobay and Vioxx.