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.
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.
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?
The National Institutes of Health provides detailed information
for patients considering participating in a clinical trial
on their web site in the section entitled
"An Introduction to Clinical Trials."
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