Pharmacology - Drug Development (part 2)

Clinical testing starts with Phase I studies on healthy subjects and seeks to determine whether effects observed in animal experiments also occur in humans. Dose-response relationships are determined. In Phase II, potential drugs are first tested on selected patients for therapeutic efficacy in those disease states for which they are intended.

Should a beneficial action be evident and the incidence of adverse effects be
acceptably small, Phase III is entered, involving a larger group of patients in
whom the new drug will be compared with standard treatments in terms of therapeutic outcome. As a form of human experimentation, these clinical trials are subject to review and approval by institutional ethics committees according to international codes of conduct (Declarations of Helsinki, Tokyo and Venice). During clinical testing, many drugs are revealed to be unusable. Ultimately, only one new drug remains from approximately 10,000 newly synthesized substances. The decision to approve a new drug is made by a national regulatory body (Food & Drug Administration in the U.S.A., the Health Protection Branch Drugs Directorate in Canada, UK, Europe, Australia) to which manufacturers are required to submit their applications. Applicants must document by means of appropriate test data (from preclinical and clinical trials) that the criteria of efficacy and safety have been
met and that product forms (tablet, capsule, etc.) satisfy general standards of quality control.

Following approval, the new drug may be marketed under a trade name
(p. 333) and thus become available for prescription by physicians and dispensing by pharmacists. As the drug gains more widespread use, regulatory surveillance continues in the form of post-licensing studies (Phase IV of clinical trials). Only on the basis of long-term experience will the risk: benefit ratio be properly assessed and, thus, the therapeutic value of the new drug be determined.