Introduction

Before a pharmaceutical company can initiate testing in humans, it must conduct extensive preclinical or laboratory research. This research typically involves years of experiments in animal and human cells. The compounds are also extensively tested in animals. If this stage of testing is successful, a pharmaceutical company provides this data to the Food and Drug Administration (FDA), requesting approval to begin testing the drug in humans. This is called an Investigational New Drug application (IND).

How are experimental drugs tested in humans?

The clinical testing of experimental drugs is normally done in three phases(Phase I, Phase II, and Phase III), each successive phase involving a larger number of people. Once the FDA has granted a New Drug Approval (NDA), pharmaceutical companies also conduct post marketing or late phase III/phase IV studies.

Phase I

Phase I studies are primarily concerned with assessing the drug's safety. This initial phase of testing in humans is done in a small number of healthy volunteers (20 to 100), who are usually paid for participating in the study. The study is designed to determine what happens to the drug in the human body--how it is absorbed, metabolized, and excreted. A phase I study will investigate side effects that occur as dosage levels are increased. This initial phase of testing typically takes several months. About 70 percent of experimental drugs pass this initial phase of testing.

Phase II

Once a drug has been shown to be safe, it must be tested for efficacy. This second phase of testing may last from several months to two years, and involve up to several hundred patients. Most phase II studies are randomized trials. One group of patients will receive the experimental drug, while a second "control" group will receive a standard treatment or placebo. Often these studies are "blinded"--neither the patients nor the researchers know who is getting the experimental drug. In this manner, the study can provide the pharmaceutical company and the FDA comparative information about the relative safety of the new drug, and its effectiveness. Only about one-third of experimental drugs successfully complete both phase I and phase II studies.

Phase III

In a phase III study, a drug is tested in several hundred to several thousand patients. This large-scale testing provides the pharmaceutical company and the FDA with a more thorough understanding of the drug's effectiveness, benefits, and the range of possible adverse reactions. Most phase III studies are randomized and blinded trials.

Phase III studies typically last several years. Seventy to 90 percent of drugs that enter phase III studies successfully complete this phase of testing. Once a phase III study is successfully completed, a pharmaceutical company can request FDA approval for marketing the drug.

Post-Marketing -- Late Phase III/Phase IV Studies

In late phase III/phase IV studies, pharmaceutical companies have several objectives: (1) studies often compare a drug with other drugs already in the market; (2) studies are often designed to monitor a drug's long-term effectiveness and impact on a patient's quality of life; and (3) many studies are designed to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies.

Who pays for clinical research?

Funding for studies comes from private industry (pharmaceutical and biotech companies). The sponsor of the research hires physicians to conduct the clinical trial. Physicians are often paid on a per patient basis. The medical care is often provided free to the patient. Patients may also be compensated/reimbursed to participate in a clinical trial.