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).
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
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
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.
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
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?
For a comprehensive listing of COPD Clinical Trials,