Testing New Drugs
Thousands of chemicals, both synthetic and extracted from "natural" sources, are being examined in the hope of finding new drugs with which to combat human and veterinary diseases. The first step is to use laboratory tests to find if these substances have a significant effect on, for example:
- cells growing in tissue culture
- laboratory animals such as rats and mice.
If the drug achieves the desired effect in laboratory animals, without killing them in the process, the drug developer applies to the U. S. Food and Drug Administration for an IND, an investigational new drug application. Granting of an IND allows testing in humans to begin. This occurs in three phases.
A small group (20–100) of healthy volunteers is given the drug to see
- if it is safe
- how quickly it is absorbed, metabolized, and excreted from the body
A group (up to several hundred) of volunteer patients with the disease are given the drug to see
- how effective it is against the signs and symptoms of the disease
- what doses are best
- what side effects may occur
A control group of similar size is given a dummy drug (placebo). Ideally the trials are "blinded" with neither the subjects (nor the investigator) knowing which pill a subject is receiving.
Hundreds to thousands of patients with the disease are given the drug to get more reliable data on its
- best dose
- rare side effects
all compared with the drug(s) that are currently used for the disease.
If all goes well, the drug manufacturer applies to the Food and Drug Administration for an NDA, a new drug application. If it is granted, the generic name of the drug is replaced by a brand name chosen by the manufacturer. For example, one of the first drugs used against AIDS was azidodideoxythymidine (AZT). When placed on the market, this name was replaced by the brand name Retrovir®.
Even after a drug is available for prescription, its use is carefully monitored and unexpected side effects are reported. Continuing oversight of an approved drug is called postmarketing surveillance or Phase IV trials.