The drugs we have come to rely on in treating and preventing disease usually have their beginnings in basic physiological research, often at cellular and molecular levels. It may be that a new family of drugs is developed using cells in tissue culture (in vitro, or outside the body). For example, cell physiologists, studying membrane transport, may discover that a particular drug blocks membrane channels for Ca++. Based on their knowledge of physiology, other scientists may predict that a drug of this nature could be useful in the treatment of hypertension (high blood pressure). This drug may then be tried in experimental animals.

If a drug is effective at extremely low concentrations in vitro, there is a chance that it may work in vivo (in the body) at concentrations low enough not to be toxic (poisonous). This possibility must be thoroughly tested utilizing experimental animals, primarily rats and mice. More than 90% of drugs tested in experimental animals are too toxic for further development. Only in those rare cases when the toxicity is low enough in experimental animals may development progress to human/clinical trials.

In phase I clinical trials, the drug is tested on healthy human volunteers. This is done to test its toxicity in humans and to study how the drug is handled by the body--how it is metabolized, how rapidly it is removed from the blood by the liver and kidneys, how it can be most effectively administered, and so on. If no toxic effects are observed, the drug can proceed to the next stage. In phase II clinical trials, the drug is tested on the target human population (for example, those with hypertension). Only in those exceptional cases where the drug seems to be effective but has minimal toxicity does testing move to the next phase. Phase III trials are conducted in many research centers across the country to maximize the number of test subjects involved. At this point, the test population must include large numbers of subjects of both sexes, as well as people of different ethnic groups. In addition, people are tested who have other health problems besides the one the drug is intended to benefit. For example, those who have diabetes in addition to hypertension would be included in this phase. If the drug passes phase III trials, it goes to the Federal Drug Administration (FDA) for approval. Phase IV trials tests other potential uses of the drug.

A very low percentage of drugs make it all the way through theses trials to eventually become approved and marketed--and, as you might imagine, the process is slow. While rigorous standards must be maintained to protect people from drugs that do more harm than good, the FDA has come under attack for not making certain drugs (for AIDS and cancer, for example) available to the public more quickly.