In October 2004, drug manufacturer Merck & Co. removed its mega-popular arthritis medication, Vioxx®, from the market because it was shown to increase the risk for heart attack and stroke. Soon after, reports of similar potential side effects of other pain relievers hit the headlines, stirring fears about the safety of prescription drugs as a whole. As a result, the Food and Drug Administration (FDA), the government agency responsible for ensuring drug efficacy and safety, among other things, is under intense scrutiny. How does the FDA test for drug safety, and therefore patient safety, before a drug gets to market and afterwards?
Moving a drug through the drug development process takes time and an abundance of testing. On average, it takes 10-15 years for a drug to complete the journey from the laboratory all the way through the FDA drug approval process. What happens along the way is a complex, precise set of hurdles and tests that a drug must pass before it is deemed safe and effective for treating a medical condition.
Once a drug is discovered or created and deemed worthy of further investigation, extensive laboratory and animal tests are the first order of business. This step in the process, called pre-clinical testing, can take up to six years. In animal testing, researchers are looking to see what effects—both beneficial and harmful—a drug may have in a living organism.
Four Phases of Clinical Testing
If pre-clinical testing issues positive results, a drug will move on to clinical testing in humans. All new drugs must pass through 3-4 orderly phases of clinical testing. The FDA does not conduct the clinical trials. Instead, it requires the drug’s manufacturers to perform increasingly rigorous tests designed to gain information about the drug’s efficacy and safety, while at the same time protecting those involved in the study. Each facility where the study is performed has its own objective drug safety review board that oversees the trial. Its job is to determine the specifics of how the study is conducted, monitor patients for side effects, and otherwise ensure patient safety. The FDA can put a hold on clinical testing at any point in the process if it believes a study is unsafe. It can mandate that a test be repeated, expanded, or that an additional clinical study is required before approval. The FDA is under no legal obligation to approve any drug or treatment.
In Phase I clinical testing, a relatively small number of volunteers, perhaps 10–80 people, receive the drug with the primary goal of determining whether it is safe to use in people. Usually, several different treatment doses and/or strategies are tested. Phase I tests usually require about 1–2 years to complete.
The goal of Phase II clinical testing is to continue testing safety while looking for the first signs of whether the drug offers any benefits. About 100–300 patient volunteers participate in these two-year phase II trials. These volunteers are often seeking an alternative approach to treatment.
Phase III clinical tests are the most rigorous of all—their goal being to monitor side effects and efficacy with long-term use. The FDA reviews this phase of clinical testing most closely in order to decide whether a drug should be approved. Usually, about 1000–5000 volunteer patients are involved in a Phase III clinical test. According to the FDA, Vioxx® was studied in about 5000 people prior to its marketing approval and did not produce an increased risk for the cardiovascular complications that surfaced in later studies. However, there is some lingering debate about whether the study’s publishers presented the data in a totally straightforward manner.
Phase III clinical tests can take up to 3-4 years to complete. Upon completion, the clinical data is extensively analyzed and compared to see if the drug offers any benefits or has any harmful side effects. If Phase III clinical results show a drug’s benefits outweigh its side effects, it is then formally submitted to the FDA, which will decide its fate. On average, the FDA takes an additional 1-1/2 to 2 years to review the clinical testing information before deciding whether a drug is safe and effective and worthy of marketing approval. During this time, it pays special attention to the recommendations of its advisory committees—groups of FDA experts with particular expertise in the medical condition the drug is intended to treat.
Clinical testing does not necessarily stop once a drug is FDA-approved. It was this type of clinical study, sometimes called a Phase IV study, where researchers became convinced of Vioxx’s troubling side effects. Phase IV trials are conducted to learn more about the drug’s long-term risks, benefits, and optimal use, or to test the product in different groups of people.
Rarely, as in the Vioxx® case, the results of these trials may sometimes cause a drug to be voluntarily withdrawn from the market by its manufacturer. In other cases, the FDA issues a warning letter to physicians about newly discovered information about a drug or, if necessary, revokes the drug’s marketing license outright after its approval. More commonly, though, these trials support earlier findings and may add important cautionary information about use with other medications or in the presence of other medical conditions.
Please be aware that this information is provided to supplement the care
provided by your physician. It is neither intended nor implied to be a
substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER
IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the
advice of your physician or other qualified health provider prior to
starting any new treatment or with any questions you may have regarding a