Islamic Center of Southern California

International Ethical Guidelines for Biomedical Research Involving Human Subjects

Appendix 3

The Phases of Clinical Trials of Vaccines and Drugs

Vaccine Development

Phase I refers to the first introduction of a candidate vaccine into a human population for initial determination of its safety and biological effects, including immunogenicity. This phase may include studies of dose and route of administration, and usually involves fewer than 100 volunteers.

Phase II refers to the initial trials examining effectiveness in a limited number of volunteers (usually between 200 and 500); the focus of this phase is immunogenicity.

Phase III trials are intended for a more complete assessment of safety and effectiveness in the prevention of disease, involving a larger number of volunteers in a multi-center adequately controlled study.

Drug Development

Phase I refers to the first introduction of a drug into humans. Normal volunteer subjects are usually studied to determine levels of drugs at which toxicity is observed. Such studies are followed by dose-ranging studies in patients for safety and, in some cases, early evidence of effectiveness.

Phase II investigation consists of controlled clinical trials designed to demonstrate effectiveness and relative safety. Normally, these are performed on a limited number of closely monitored patients.

Phase III trials are performed after a reasonable probability of effectiveness of a drug has been established and are intended to gather additional evidence of effectiveness for specific indications and more precise definition of drug-related adverse effects. This phase includes both controlled and uncontrolled studies.

Phase I and phase II trials must be comply with Section C (articles 28-32) of the Helsinki Declaration, which deals with medical research combined with medical care.

Phase IV trials are conducted after the national drug registration authority has approved a drug for distribution or marketing. These trials may include research designed to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. Phase IV trials may also be designed to evaluate a drug in a population not studied adequately in the pre-marketing phases (such as children or the elderly) or to establish a new clinical indication for a drug. Such research is to be distinguished from marketing research, sales promotion studies, and routine post-marketing surveillance for adverse drug reactions in that these categories ordinarily need not be reviewed by ethical review committees (see Guideline 2). Islamic Center of Southern California