Medical research studies designed to answer scientific questions and to find better ways to prevent, detect, or treat disease. A large number of clinical trials are confined to testing the safety and efficacy of new medicines.
There are generally four separate phases of such trials
Phase I trials
: Phase I studies will be the first time human subjects are exposed to the potential new medicine. The objectives of the study will be to investigate pharmacodynamics, dose-response, and in the case of vaccines, immune response, and to determine the maximum dose that can be tolerated by participants. In the case of most new medicines these studies will be undertaken in a small number of healthy volunteers. Evidence for the efficacy of the medicine would not normally be provided by Phase I studies.
Phase II trials
: Using the information about the safe dosage range obtained from the Phase I studies, the compound will be administered to patients suffering from the target disease. Significant numbers of individuals will be recruited into the trial at a number of clinical centres. The objective of the Phase II studies will be to seek evidence of the efficacy of the medicine against the specific disease. More information about the safety of the medication will emerge from these studies as larger numbers of individuals are exposed to the medicine. In Phase II trials, the patient will often be randomly assigned to the novel treatment group or to a group receiving a placebo (a compound possessing no therapeutic effect) or, more usually, a conventional and established treatment.
Phase III trials
: Where a compound has shown evidence of efficacy without significant side effects, it will enter Phase III trials. Many hundreds, or sometimes a few thousand patients will be enrolled. These trials will generally seek not only to confirm the clinical efficacy of the novel compound, but also to establish its efficacy in comparison to existing treatments. These studies will often be multicentre and sometimes undertaken on an international basis. Again, careful attention is paid to possible side effects as larger numbers of patients are exposed to the intervention. The end-points for Phase III studies include the demonstration of a statistically significant improvement in the efficacy of the novel medicine over the established therapies, if any such exist.
Phase IV trials
: Once a new medicine reaches the market it will be subjected to postmarketing surveillance in order to identify side-effects and other adverse effects which would only become evident as much larger numbers of individuals are treated. In addition, formal clinical trials continue in order to develop a greater understanding of the compound and its effects in a wider clinical environment. Further study may also extend its use for other indications or for different patient groups, such as children or the elderly. Special study designs may be used according to the objectives of the study to evaluate safety or efficacy. These may include study of temporal trends, case-control studies, or the phased introduction of an intervention in different areas. Phase IV studies may also be designed to measure the impact of the intervention on the epidemiological pattern or the transmission of an infectious disease.
Nuffield Council on Bioethics. The Ethics of Research Related to Healthcare in Developing Countries. Nuffield Council on Bioethics, The Dorset Press, London, 2005.