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This article was published in U.S. 1 Newspaper on December 8,
1999. All rights reserved.
Safe Drug Development
Just why is getting a drug to market so expensive? A
course for physicians who work in the pharmaceutical industry will
explain why. Explore the world of clinical protocols and
at a two-day seminar conducted by the Center for Professional
at the New Brunswick Hyatt, Thursday, December 9, 8:30 a.m. Cost $800.
Call 732-613-4500 or go to http://www.cfpa.com.
The course will cover government regulations pertaining to clinical
protocols with a focus on drug research. Denise T. Resnik, a
pharmaceutical industry consultant, will be presenting with
Greenslade, founder of Intercare, a resource to the pharmaceutical
industry, and Edward H. Wolf, a statistics professor at Baruch
College, City University of New York.
First on the agenda will be how a clinical program is designed toward
the goal of getting a drug approved for a particular use or
Second will be the design of a protocol, the document that clearly
defines all of the parameters of investigation. "The protocol
specifies which drug is being investigated, who the subjects or
are, and how they will be studied," says Resnik.
"The protocol also sets forth how long the patients will be
what doses of drug will be used, what kind of safety precautions will
be taken for the welfare of the patients or subjects, where the study
will be conducted, who is conducting the study, what the regulatory
environment is, and what the constraints are for conducting the
trial, within the program." The third consideration is managing
the studies where the protocols are being carried out.
The four phases in the approval process for a new drug:
and in "in-vitro" (studies conducted on a cellular level,
not requiring human beings as patients), a drug company will go to
the Food and Drug Administration (FDA) to request permission to study
a novel compound. If the FDA grants permission for further study based
on the strength of the animal investigations, it will grant approval
to study the drug in healthy normal volunteers.
Individuals participating in the first phase of clinical trials are
known as subjects, not patients. Dosage amounts are low. "Healthy
individuals are considered the most resistant to anything if there
would be a severe reaction to the drug. Phase 1 studies are done in
hospitals starting at a very low dose on a small number of patients.
In this phase what investigators are looking for is not efficacy
the drug works against a particular disease) but to get a sense of
the drug’s safety," says Resnik.
with patients who have not responded well to other medications in
their class. Resnik uses a fictitious new drug for hypertension to
illustrate her point. "Many hypertensive patients are on multiple
drugs and their blood pressure is still not controlled. A Phase 2
study will afford an opportunity for that patient to see if a
works — since no medications that work for everybody."
and some efficacy information is available. Phase 3 studies are much
broader studies involving several thousand patients across the
A large number of people with a disease, like hypertension, would
involve between 5,000 and 10,000 patients. Much rarer diseases require
Phase 3 studies with fewer patients. These studies let many patients
and many physicians get experience with the drug, and they may be
conducted in outpatient clinics and private doctors’ offices.
The big concern is whether a drug may have a very small instance of
severe side effects, occurring very infrequently, say one in 10,000
cases, says Resnik. "In controlled clinical studies, you may not
have 10,000 patients. The severe side effect may not have occurred
or may have occurred only once, and it may not be clear that the side
effect was caused by the drug. But when the drug gets approved, then
one in 10,000 is a very large number. The diet drug combination
and Thalidomide fall into this category."
the drug company wants to compare its drug to the benchmark drug in
that class of compounds that have been approved. So head-to-head
is usually done in Phase 4.
studies? It begins with the doctors. "Physicians are provided
with a fair amount of information to make a decision about whether
they want to participate in a study. Studies are always done very
carefully, with the patients’ well-being in mind. The patient is given
all the information in order for them to made an intelligent decision
as to whether to participate in the study or not," says Resnik.
There is another layer of protection for study participants. An
review board is usually convened at the hospital or university where
the study is being conducted. Before an individual investigator can
conduct a clinical study, the institution or medical center where
the study is to be conducted has to approve the study. There is a
written consent that a patient has to read and sign indicating the
information known about a drug at the time of the study, and what
the possible side effects are. The patient provides emergency contact
information. "Signing the document does not mean they have
any rights that they would have. If the patient has a relationship
with the physician, they will be more willing to participate,"
What about patients receiving money as an enticement to participate
in a clinical study? We have all heard the advertisements on the radio
for medical trial volunteers that offer some sort of incentive.
the old days, study subjects were inmates, and around the 1960s it
was decided that these were people not making decisions on their own
free will — that they were indeed being coerced." Typically,
out-of -pocket expenses will be reimbursed if a patient has to take
a bus or a taxi, but lost wages are not. "Nobody wants to leave
the impression that patients can make money through their
in the tests."
Based in East Brunswick, with a European headquarters in the
the Center for Professional Advancement was established in 1967 by
Charles Bendel. It offers intensive two- to five-day courses at a
post graduate level for scientist and engineers. Instructors emphasize
practical technlogy rather than theory. The CFPA courses, in 19
areas ranging from food technology to plant engineering, offer
by many trade organizations. In particular, more than 130
courses are offered annually through the CFPA’s sister organization,
the Institute for Applied Pharmaceutical Sciences. The CFPA’s favored
New Jersey venue is the New Brunswick Hyatt.
The daughter of an engineer and a medical school administrator, Resnik
has a BA in biology from Clark University and an MS in pharmacology
from Northeastern University; she began her career at Harvard Medical
School in 1976. She has worked at Astra Pharmaceuticals in animal
and clinical research and at Ives Laboratories (American Home
For Pfizer she managed a cardiovascular program and integrated safety
sections for regulatory submissions. In 1982 she established her
practice in Yonkers, where she lives with her husband and two teenage
sons. Resnik traces her interest in science to the Bronx High School
of Science and summer internship programs at Columbia College of
and Surgeons doing pharmacology research. "I found that I like
working with animals more than I liked working with test tubes."
Resnik feels that compared to days gone by, the patient has become
the central figure in the entire drug approval process. "It used
to be much more the investigator, and I think now patient safety and
the effort in making information available to them is much
— Jeff Lippincott
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