drugs
Drug Design and Development
Stages of Drug Development
(See table From Laboratory to Medicine Cabinet for a summary of the stages of drug development.) After a drug that may be useful in treating a disorder is identified or designed, it is studied in laboratory animals (a phase called early development). Early development gathers information about how the drug works, how effectively it works, and what toxic effects it produces, including possible effects on reproductive capacity and the health of offspring. Many drugs are rejected at this stage because they are shown to be not effective or too toxic. If a drug seems promising after early development, a program describing the clinical study must be approved by an appropriate institutional review board (IRB) and an investigational new drug (IND) application is filed with the Food and Drug Administration (FDA). If the FDA approves the application, the drug is allowed to be tested in people (a phase called clinical studies). These studies occur in several phases and only in volunteers who have given their full consent. Three phases of clinical studies are required for FDA approval: Phase 1 evaluates the drug's safety and toxicity in people. Different amounts of the drug are given to a small number of healthy young people to determine the dose at which toxicity first appears. Phase 2 evaluates what effect the drug has on the target disorder and what the right dose might be. Different amounts of the drug are given to up to about 100 people who have the target disorder to see whether there is any benefit. Just because a drug is effective in animals in early development does not mean it is effective in people. Phase 3 tests the drug in a much larger (often hundreds to thousands) group of people who have the target disorder. These people are selected to be as similar as possible to the people who might use the drug in the real world. The drug's effectiveness is studied further, and any new side effects are noted. Phase III tests usually compare the new drug against an established drug, a placebo, or both. In addition to determining a drug's effectiveness, studies in people focus on the type and frequency of side effects and on factors that make people susceptible to these effects (such as age, sex, other disorders, and the use of other drugs). If studies indicate that the drug is sufficiently effective and safe, a new drug application (NDA)—including data from the animal and human tests, intended drug manufacturing procedures, prescribing information, and product labeling—is filed with the FDA, which reviews all the information and decides whether the drug is sufficiently effective and safe to be marketed. If the FDA approves, the drug becomes available for use. The whole process usually takes about 10 years. On average, only about 5 out of 4,000 drugs studied in the laboratory are studied in people, and only about 1 out of 5 drugs studied in people is approved and prescribed. Each country has its own approval process, which may be different from the process in the United States. Just because a drug is approved for use in one country does not mean that it is available for use in another country. After a new drug is approved, phase 4 studies are sometimes done; the manufacturer must monitor the use of the drug and promptly report any additional, previously undetected side effects to the FDA. Doctors and pharmacists are encouraged to participate in the ongoing monitoring of the drug. Such monitoring is important because before the drug is marketed, even comprehensive studies can detect only relatively common side effects (that occur about once in every 1,000 people). Important side effects that occur once in every 10,000 (or more) people can be detected only when a large number of people use the drug, that is, after it is on the market. The FDA may withdraw approval if new evidence indicates that a drug may cause severe side effects. For example, the diet aidfenfluraminewas withdrawn from the market because some people who took it developed serious heart disorders. 