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, 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 three/phase four studies.

A Phase One Study:

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.

A Phase Two Study:

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.

A Phase Three Study:

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 Three/Phase Four 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 clinical research comes from both the federal government (through the National Institutes of Health) and private industry (pharmaceutical and biotech companies). The sponsor of the research hires physicians, who may work in a wide variety of health-care settings, to conduct the clinical trial. Physicians are typically paid on a per-patient basis. The medical care is often provided free to the patient. Patients may also be paid a small fee to participate in a clinical trial.

Should you participate in clinical research?

People participate in clinical research for a variety of reasons. People who volunteer for phase II and phase III trials can gain access to promising drugs long before these compounds are approved for the marketplace. They typically will get excellent care from the physicians during the course of the study. This care also may be free.

The patient's rights and safety are protected in two important ways. First, any physician awarded a research grant by a pharmaceutical company or the NIH must obtain approval to conduct the study from an Institutional Review Board. The review board, which is usually composed of physicians and lay people, is charged with examining the study's protocol to ensure that the patient's rights are protected, and that the study does not present an undue or unnecessary risk to the patient. Second, anyone participating in a clinical trial in the United States is required to sign an "informed consent" form. This form details the nature of the study, the risks involved, and what may happen to a patient in the study. The informed consent tells patients that they have a right to leave the study at any time.

Patients considering participating in clinical research should talk about it with their physicians and medical caregivers. They also should seek to understand the credentials and experience of the individuals and the facility involved in conducting the study.

Other questions to ask include:

• How long will the trial last?

• Where is the trial being conducted?

• What treatments will be used and how?

• What is the main purpose of the trial?

• How will patient safety be monitored?

• Are there any risks involved?

• What are the possible benefits?

• What are the alternative treatments besides the one being tested in the trial?

• Who is sponsoring the trial?

• Do I have to pay for any part of the trial?

• What happens if I am harmed by the trial?

• Can I opt to remain on this treatment, even after termination of the trial?

Where can you get more information about clinical research?

For more detailed information about participating in clinical trials, please refer to the CenterWatch publication Informed Consent: A Guide to the Risks and Benefits of Volunteering for Clinical Trials. Recommended by the Institute of Medicine, Informed Consent has been featured in major health magazines, newspapers, national public radio and television.