The process of introducing a new drug treatment to market involves
a series of progressive steps and is a long and complex process.
It generally takes about 10 years for a drug to be approved.
Preclinical studies are
the first step in the drug development process. Initially the
Sponsor
tests a new substance
in vitro
in a laboratory setting.
Then animal studies with the investigational drug are conducted in
order to determine safety and how the drug works in the body.
Finally researchers investigate lethal doses of the
investigational product
prior to the Phase I trials. These studies
are approximately 1-3 years in duration.
Next
the sponsor requests
FDA
approval to begin testing the
investigational drug in humans. The request is called an
Investigational New Drug Application (IND)
. Approval of the
IND
is given only after the scientific and ethical merits of the
supporting research and the proposed Phase I study have been
evaluated in-depth and experts concur with the company’s
recommendation to move forward.
There are four main phases
of testing in human subjects. Phase I studies are the initial
introduction of an investigational new drug into humans. These
trials are closely monitored and may be conducted in patients or
normal volunteer subjects. They are designed to determine the
metabolism and pharmacological actions of the drug in humans, the
side effects associated with varying doses and, if possible, to
gain early evidence on
efficacy
. The total number of subjects who
participate in this initial phase varies with the drug, but is
generally in the range of 20-80 volunteers. In this phase of
clinical trials the patient receives open label medication and
there is no placebo (inactive substance) involved.
Phase
II trials are
controlled clinical
studies that are conducted
primarily to evaluate the drug’s effectiveness in treating or
preventing the illness. These studies attempt to determine the
common short-term
adverse events
and risks associated with the
drug. They are well controlled, closely monitored, and conducted
in a relatively small number of patients, usually involving no
more than several hundred subjects. Second phase studies are
sometimes placebo-controlled and often double-blinded where
neither the patient nor the medical personnel know if a placebo
or the medication is being prescribed. Subjects are generally
restricted from taking any additional medications in these types
of studies.
Phase III studies are performed after the preliminary evidence
obtained has indicated
effectiveness
of the drug. At this study
phase the focus is on gathering additional information about
safety and
efficacy
in order to evaluate the overall benefit-risk
relationship of the drug and to provide an adequate basis for
physician labeling. Study criteria are generally more relaxed at
this phase. Subjects diagnosed with concurrent illnesses and
taking additional medications may be included depending on the
type of study.
The New Drug Application (NDA)
is a request from the
Sponsor
for
FDA
approval to market the investigational drug. Results from the
Phase I, II, and III trials supporting safety and efficacy are
submitted to the
FDA
. Ongoing preclinical study data are reported
and information on drug formulation and drug manufacturing are
included.
Phase IV (post-marketing)
studies delineate additional information about the drug’s risks,
benefits, and optimal use. At this phase the drug may be compared
to other drugs already on the market. These
studies are often designed to monitor a drug’s long term
effectiveness and impact on a patient’s quality of life. Also many
of these 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 private industry
(pharmaceutical and biotech companies) and the federal government
(through the National Institutes of Health). The
Sponsor
of the
research hires physicians, who may work in a wide variety of
health-care settings, to conduct these trials.
Next
the sponsor requests
Phase
II trials are
