For pharmaceutical companies, the stakes in developing new drugs are high. The journal Health Affairs estimates the cost to develop a new drug ranges from $500 million to $2,000 million. Of all the drugs introduced to the marketplace, only 30 percent make enough money to return their research and development costs.
Preclinical Testing
Before a newly discovered drug can be tested on humans, preclinical studies test the drug's safety and toxicity levels. Although scientists sometimes use cell and tissue cultures for parts of this process, animal testing is still necessary. The goal of preclinical testing is to determine at what point the drug is toxic, as well as long-term effects. Reproduction problems and cancer-causing activity are also studied. Preclinical testing can take anywhere from two to six years.
Clinical Trials
Drug manufacturers must file a Notice of Claimed Investigational Exemption for a New Drug, also referred to as an IND, with the Food and Drug Administration (FDA) before a drug can be tested in humans. It can take anywhere from four to six years to complete the trials and analyze the data. Clinical trials consist of four phases.
Phase 1
In phase 1 testing, 25 to 50 healthy volunteers are given the drug. The object of phase 1 is to determine the highest dose that can be tolerated. Drugs that are expected to have serious side effects, such as those used to treat cancer or AIDS, are given to volunteers who already have the disease.
Phase 2
Phase 2 testing uses 100 to 200 volunteers who have the disease the drug is targeting. The volunteers are usually divided into three groups. The investigators then compare the effect of the investigational drug to that of a placebo (sugar pill) along with a drug that is already approved for the disease being targeted. To prevent unintentional bias when they report side effects and efficacy, volunteers are not told which substance they are being given.
Phase 3
Phase 3 testing is conducted on thousands of volunteers with the target disease. These are usually double-blind studies, which means neither the volunteers nor the investigators know whether the volunteer is taking the active drug or the placebo. This improves the objectivity of the investigators as they record data. Information on which volunteers are taking the active drug is held by a third party until the testing is complete. If phase 3 testing is successful, the drug manufacturer will file a New Drug Application, or NDA, with the FDA. The NDA must include all the data collected in all the clinical trials. The FDA analyzes the data to determine whether the drug can be marketed in the United States. This process can take months to years. The average time for an NDA is 12.9 months.
Phase 4
Many adverse effects do not occur until the drug is used by large numbers of people in the general population, so phase 4 begins after a drug is available on the market. In this phase, the drug is monitored for adverse effects that did not occur during clinical trials. Phase 4 depends on reporting by physicians on possible side effects and toxicities. There is no set time frame for phase 4.
References
- Health Affairs: Estimating the Cost of New Drug Development
- "Basic and Clinical Pharmacology;" B. Katzung; 2007
