A new medication can be prescribed or sold over
the counter only after it is approved by the
Food and Drug Administration or FDA. The development
of a new drug is a long and complicated process.
The role of the doctors, nurses, and other support
staff is a critical one. Most of the drugs in
use today have, after their initial discovery,
undergone a range of laboratory tests using
cell cultures, isolated tissues, and animals.
If a drug shows clinical potential, it may be
used in humans only after successful completion
of pre-clinical toxicity tests on different
animal species. For the 50,000 or so substances
which are synthesized in the laboratory, approximately
five will reach the stage of full tests in humans-only
one of these will actually be safe and effective
enough to be marketed. In order for the FDA
to approve a medication, the pharmaceutical
company must show that the medication is both
safe and effective for use in the treatment
for which it is intended. To show this efficacy
and safety the pharmaceutical company will spend
many years conducting a series of studies. The
clinical testing of experimental drugs is normally
done in four phases, each successive phase involving
a larger number of people.
Phase I — Phase I studies
are primarily concerned with assessing the drug's
safety in healthy volunteers. 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 — Phase II study is
conducted once a drug is proven 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 — Phase III
study is conducted and 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.
Phase IV — Phase IV studies
are performed after obtaining a license to market
the drug. Contrary to Phases II and III, problems
associated with long term use of the drug or
rare adverse events can be detected. 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.
