During the long development process, substances that are identified in basic research need to pass pre-clinical and clinical tests. Most do not advance through our rigorous testing standards, but those that do may offer a chance for a better life for patients.

In basic research, biochemists and molecular and cell biologists with an understanding of the pathophysiology of human diseases identify the research and drug targets:

• Start with a study of the normal and abnormal body functions.
• Investigate each component of a disease, such as the symptoms, causes, the organ affected and the biochemical pathways.
• Together with the information obtained in previous research and publications, find out at which step we can stop the disease from progressing or developing — this is our target.
• Search for a drug compound that is active against the target. Compounds can be chemically synthesized, biologically synthesized or computer simulated.
• Isolate the compound.
• Perform animal testing to obtain safety data pertaining to toxicity and carcinogenicity.
• Gain regulatory approval to test in humans.

Clinical trials are large and complex. The number of patients in a new drug trial has increased from about 1,300 in the early 1980s to more than 4,000 for a typical new medicine today. And, in an indication of the growing complexity of what we are trying to measure, the number of medical procedures per patient in trials, such as blood tests and other measurements, also has gone up, from about 100 in the early 1990s to more than 140 today.

Phase 1: Safety
Involves 20-100 healthy volunteers who take a drug for about 1 month.
Purpose: Obtain information about drug absorption and metabolism, effects on organs and tissues, and side effects at different dosages.

Phase 2: Efficacy
Involves several hundred volunteer patients (people with the disease).
Purpose: Learn about the effectiveness of the drug in treating the disease and any short-term side effects in patients.

Phase 3: Large-scale testing
Involves hundreds or thousands of patients; involves treatment and control arms.
Purpose: Seek the benefit/risk relationship of the drug, as well as any less-common and long-term side effects; develop labeling information.

Phase 4: Ongoing surveillance
Involves large numbers of health-impaired patients; usually performed after drug approval and related to the approved indication.
Purpose: To support the use of the approved indication; to prove safety and efficacy in new indications; to test new dosage strengths; and to collect and analyze long-term safety data.