Background Information on Clinical Research

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 3 phases, each successive phase involving a larger number of people. Once the Food and Drug Administration has granted a New Drug Approval (NDA), pharmacuetical 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 (twenty 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 placebo. Often these studies are "blinded"--neither the patients or the researchers know whom are 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 1/3 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 drugs longterm 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 bio-tech 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 free 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 NHI must obtain approval to conduct the study from an Institutional Review Board. The review board which is usually composed of physicians and lay peopl, 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 U.S. 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 alternate 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? The National Institutes of Allergy and Infectious Disease at the National Institutes of Health provides detailed information for patients considering participating in a clinical trial on their web site in the section entitled "What Is A Clinical Trial?"

Glossary of clinical research terms: Clinical Trial A carefully designed investigation of the effects of drug, medical treatment, or device on a group of patients. Clinical Investigator A medical researcher in charge of carrying out a clinical trial's protocol. Researchers are usually doctors, nurses, pharmacists or other health care professionals. Coordinator This individual manages the conduct of the clinical trial. Food and Drug Administration A government agency that enforces laws on the manufacture, testing, and use of drugs and medical devices. All drugs and medical devices must be approved by the FDA before they can be used by the general public. Informed consent A discussion of all procedures, benefits, risks, and expectations of a clinical trial between clinical investigators and potential patients. The FDA requires all patients to sign an informed consent form before participating in a trial. Institutional Review Board (IRB) A board consisting of health care professionals from the institution where the clinical trial takes place, as well as members of the local community. The board scrutinizes all trial activities including recruitment, advertising, and potential risks. The IRB also makes sure that FDA regulations are being followed in a particular trial. Investigational treatment The drug or medical device that is tested during a clinical trial. Phases Drugs and medical devices must pass three segments or phases of testing before they can be eligible for FDA approval. Principal investigator A medical professional who is overseeing the treatment of the patients in the clinical trial. Protocol A plan that sets guidelines for a trial and usually involves several different trial locations. A protocol is usually designed by the sponsor of a clinical trial. Sponsor The pharmaceutical company, research institution, or other health organization that funds a clinical trial and designs its protocol. Standard treatment An FDA-approved treatment currently in wide use. In trials involving new treatments, there may be no pre-existing treatment at all. In these cases, the lack of any treatment is considered the standard treatment. Generally, the goal of a clinical trial is to introduce an investigational treatment that is safer and more effective than the standard treatment.