WV
Executive
July/August 2005
Clinical
Trials
By Julie H. Mobayed, RN, BSN, MPH and Natalie H. Tappe,
RN, BSN, MS
In
2000, the U.S. based pharmaceutical industry spent about
$26.4 billion researching and developing new drugs.
Products in Phase I, II and III clinical trials account
for 28.3 percent ($7.47 billion). An additional 5.8
percent ($1.53 billion) is allocated to Phase IV clinical
trials. About 50 percent ($4.5 billion) of the clinical
development budget is allocated to investigator services.
These services focus on patient care and recruitment, data
collection and clinical trial management. Investigators,
physicians participating in the trial, are responsible for
recruiting and management patients enrolled in the study.
Patients are the most precious commodities for the drug
development community. Without patients trials cannon
be conducted.
Research
& Development Directions reports that there are about
4,360 new products and new indications in the pipeline.
Of the $26.4 billion that was spent, about $6 billion will
be allocated to products that act on the central nervous
system; $5 billion on products to treat cancer, the endocrine
system and metabolic diseases; $4.1 billion on cardiovascular
products; $3.6 billion on infectious disease products; $1.5
billion on products affecting the respiratory system and
$900 million on products that act on the digestive and genitourinary
system.
The
future looks crowded. The increased research and development
investment of pharmaceutical companies is expected to result
in a 20-fold increase in the number of available drug targets.
The mapping of the human genome may give researchers as
many as 10,000 new drug targets.
As
a result of the significant pharmaceutical industry investment
in research and develop-
ment in the United States, the “research based U.S.
pharmaceutical industry is one of the crown jewels of the
American economy and plays a critical role in the health
and prosperity of the American people,” according
to a report by Kevin Hassett, Ph.D., American Enterprise
Institute, and Dr. Robert Shapiro, Sonecon, LLC.
The
pharmaceutical industry is and has been a “major source
of innovation in the development not only of new drugs,
but also of new manufacturing processes and scientific knowledge,”
they report. Research and Development is the engine
that drives the growth of the pharmaceutical industry.
Some
analysts may say research and development has become the
religion of the pharmaceutical industry. A company’s
ability to invest in research and development determines
everything: its sales, profits, market share, price
and shareholder value.
Hyperion
Clinical Research (HCR) has taken pieces of this economic
windfall by conducting several clinical trials in southern
West Virginia. Through HCR, West Virginia physicians
have been able to increase their revenue by participating
as a principal investigator. A principal investigator
(PI) is the medical doctor within the practice who is responsible
for conducting the clinical trial. The average revenue
per study is estimated to be approximately $40,000 to $75,000,
of which the investigator can expect 20 to 30 percent.
By conducting clinical trials, the physicians can offer
their patients access to innovative therapies not available
to the general public.
WHAT
EXACTLY IS A CLINICAL TRIAL?
Protocol
All
clinical trials are based on a set of rules called a protocol.
A protocol describes what types of people may participate
in the trial; the schedule of tests, procedures, medications,
and dosages, and the length of the study. While in
a clinical trial, participants are seen regularly by the
research staff to monitor their health and to determine
the safety and effectiveness of their treatment. Protocols
are designed prospectively and include data collection,
statistical analysis, primary outcome measurements, secondary
outcome measurements, etc.
Research
Drug Development and Testing
Pharmaceutical
companies who research and develop new drugs and devices
are required to go through a specified testing and approval
process regulated in the U.S. by the Food and Drug Association
(FDA). Typically this testing is done through clinical
trials. A clinical trial is a research study to answer
specific questions about vaccines or new therapies or new
ways of using known treatments. Clinical trials (also
called medical research and research studies) are used to
determine whether new drugs or treatments are both safe
and effective. This regulated process is divided into
“Phases” of drug develop-
ment. The clinical (human) 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.
Pre-Clinical
Before
a pharmaceutical company can initiate testing in humans
it must conduct extensive pre-clinical 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). Animal models are used
to determine safety, dosage and potential efficacy before
entering studies in humans.
Phase
I studies are primarily concerned with assessing the drug’s
safety. This initial phase of testing in humans is
done in small numbers (20 to 100) of healthy volunteers,
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.
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.
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. Upon completion of
the Phase III study, all the data accumulated is reported
back to the FDA, including the incidence of all side effects
and adverse events. The FDA then sets up an advisory
panel to evaluate the safety and efficacy of the drug or
device. If the panel recommends that the drug/device
is safe and beneficial, the FDA may approve its use in medical
practice. Once approved, the FDA grants a license
for the drug/device to be marketed or to be prescribed by
a physician to treat patients.
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.
Geographic
Area
From
Southern New York to Northern Mississippi, Appalachia includes
22 million people in 12 states. West Virginia is the
only state fully encompassed in Appalachia and Charleston,
the state capital, is the headquarters of HCR.
Patient
Demographic
Appalachia
represents the highest median age in the nation and has
one of the highest proportions of elderly (65+) population.
Our region also ranks among the highest in rates of cardiovascular
disease (4th), oncology (7th) (West Virginia ranked 1st
in rates of death due to lung cancer; colorectal and breast
cancer complete the top three), pulmonary disease (West
Virginia ranked 1st in rates of death due to COPD) diabetes
(10th), obesity (7th), renal disease, tobacco use (7th),
osteoporosis, and overall mortality rate (1st) genitourinary
system.
We
have developed a network of regional physicians and health
care institutions to conduct important clinical research
for drugs in development and to better understand health
care outcomes. Our network consists of more than 20
physicians. Our role is to provide the complete infrastructure
to conduct these studies. We provide expert personnel,
trained nurses and study coordinators to each physician
so that management of the studies does not fall solely on
the physicians. We consolidate and centralize all
core services for all investigative sites.
By
using members of our own experienced team, we minimize the
physicians’ work burden by providing the staff necessary
to implement the trial. This approach allows the physician
to focus on the patient and HCR to focus on quality data
and regulatory compliance. This is the core of our
integrated team approach.
HRC
is unique to West Virginia. Our mission is to become
one of the first regional networks for clinical research.
They will be the only West Virginia based research team
focused on Appalachian regions. Hyperion is dedicated
to bringing new medicines and advanced technologies to improve
the quality of life for the people of Appalachia.
