A clinical trial is a research study to answer 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. There are also other clinical studies, for example, psychological and nutritional studies or experiments with medical equipment, for which healthy volunteers and patients (volunteers) are required.
Clinical Trials, with the help of volunteers, are conducted in four phases:
Phase I: Research with healthy volunteers
Phase I research is usually performed with healthy volunteers and is meant to study how the medicine affects humans and to evaluate the safety. Prior to a Phase I study, animal based research on safety has to be completed with acceptable results. Most phase I research is started with a single healthy volunteer and at the lowest possible dose. When this has proven to be safe, more healthy volunteers are included and the dose is raised. In this phase, both the safety of the new medicine, as well as the way the body processes the medicine is studied. The effects of each dose are studied separately, starting with the lowest possible dose.
After the initial phase I testing, research is usually also done with treatment continued for several consecutive days. The safety of the new medicine is closely guarded by regularly testing blood pressure, heart function, as well as assessing blood and urine samples. These types of research are generally conducted in specialized phase I clinics or academic hospitals, with expertly trained personnel and according to protocols that are designed to prevent any mistakes.
Phase II: Research with patients (small group)
Phase II studies are designed to determine how well the medication works for the target population; patients diagnosed with the specific disease the medication is meant to treat. During this phase the safety of the medication will remain under close evaluation. Blood pressure, heart function, blood and urine samples will be evaluated on a regular basis, throughout the study. The efficacy of treating the patients is also studied during this phase. Research is done to determine the optimal dose: with the greatest effect on the disease and the smallest burden of side-effects.
Phase III: Treatment of patients (large group)
Phase III includes much larger numbers of patients in the research. The studies are designed to compared the new treatment to the best available treatment at the time of the study. If there is no other treatment available, the new treatment will be compared to placebo. As larger groups are included in these studies, it is possible to also evaluate side effects that are relatively rare, and occur with a frequency of 1% or less. The results of phase III research, complete the entire dossier that is submitted to the regulatory authorities for marketing approval.
Phase IV: Research with medication already on the market
Phase IV research studies treatment that have already been approved and are available to patients. These studies are designed to improve knowledge of the existing medication or to treat other indications, not included in previous research. As the medications studied in these trials usually have already been on the market for a while, much is already known about these treatments. A good example is Viagra, which was initially tested and approved as a treatment for high blood pressure. A side effect, that was reported frequently, was improved erections. The pharmaceutical company therefore researched this ‘side effect’ in a phase IV trial.