The Translation from Preclinical
Research
When a drug, procedure, or treatment has proven
itself as safe and effective in preclinical testing,
it is then considered for clinical testing in
humans. The clinical testing of experimental drugs,
procedures, or treatments in humans is normally
done in three or four phases (Phase I, Phase II,
Phase III, and Phase IV) with a greater number
of patients included in each subsequent phase.
SJTRI may be involved with any or all phases of
a clinical trial or even in post trial studies
for long-term safety.
If you elect to participate in and are admitted
into a clinical trial, you may be involved with
one or more different phases of the research being
studied. Your Clinical Research Coordinator can
discuss with you the general application of the
study, the phase being studied, and any known
side effects suspected from this phase being studied.
- Phase I Clinical Studies: Phase I studies
are primarily concerned with the drug
or treatment’s safety, and are the
first time it is tested in humans. These
studies are typically done in a small
number of healthy volunteers, usually
in a hospital setting where they can be
closely watched and treated should there
be any side effects. These volunteers
may be paid for their participation and
generally include a cross section of the
population that would be applicable to
the future use of the drug or treatment.
The purpose of these studies is generally
to determine how the experimental drug
or treatment is tolerated (absorbed, metabolized,
and excreted) in humans. Additionally,
they seek to determine what types of side
effects occur as the dosage of the drug
is increased. Any beneficial effects of
the drug are also noted.
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- Phase II Clinical Studies: Once an experimental
drug or treatment has been proven to be
safe and well tolerated in healthy volunteers,
it must be tested in the patients that
have the disease or condition that the
experimental drug is expected to improve/cure.
In addition to ensuring that the experimental
drug is safe and effective in the patient
population of interest, Phase II studies
are also designed to evaluate the effectiveness
of the drug.The second phase of testing
may last from several months to a few
years and may involve up to several hundred
patients. Most Phase II studies are well
controlled, randomized trials. That is,
one group of patients (subjects) receives
the experimental drug, while a second
"control" group receives a standard
treatment or placebo. Placement of the
subject into the drug treatment or placebo
group is by random chance (as if by the
flip of a coin). Often these studies are
"double-blinded" and neither
the patient nor the researchers (investigator,
coordinator, etc.) know who is getting
the experimental drug. Additionally, Phase
II studies are often designed to determine
the dosage with the least number of side
effects that is most effective. These
are often referred to as dose-ranging
studies. In general, the purpose of Phase
II studies is to provide the pharmaceutical
or device company and the FDA with comparative
information about the relative safety
of the experimental drug, the proper dosage
needed to treat the condition, and the
drug's effectiveness. Only about one-third
of experimental drugs successfully complete
both Phase I and Phase II testing.
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- Phase III Clinical Studies: In a Phase
III study, an experimental drug or treatment
is tested in several hundred to several
thousand patients with the disease/condition
of interest. Most Phase III studies continue
to be randomized and blinded. The large-scale
testing provides the pharmaceutical company
as well as the FDA with a more thorough
understanding of the drug's effectiveness,
benefits/risks, and range/severity of
possible adverse side effects. Phase III
studies typically last several years.
Seventy to ninety percent of drugs that
enter Phase III studies successfully complete
this phase of testing.
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- Phase IV and Beyond: After successful
completion of Phase I-III testing, a company
submits the results of all of the studies
to the FDA to obtain a New Drug Application
(NDA). Once the FDA grants a company with
a NDA, the company can market the drug
(medication) to the public. Additional
testing (post-market or late phase III/phase
IV) to further evaluate at the long-term
safety continues.
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Before moving to each next phase of development
the data collected in the current phase are carefully
analyzed to ensure the experimental research being
tested is at least safe and well tolerated. After
successful completion of Phase I-III testing,
the company or organization will submit the results
of all of the studies to the FDA to obtain a New
Drug Approval (NDA). Once the FDA grants a NDA,
the sponsoring company or organization can market
the drug (medication) or treatment to the public.
Additional testing (post-market or late phase
III/phase IV) to look at the long-term safety
continues; often well into the life of the drug
or treatment.
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