Author: Carole W. Williams, RN, MN
Author Date: 7/14/2000

Many people have questions about how new prescription drugs and
treatments become available for combating diseases such as
hepatitis. New drug development is a lengthy process that must keep
public safety at the forefront. It is also an expensive proposition
for the drug company.

A large part of the new drug development process involves clinical
trials. There are several clinical trials currently taking place to
find new and better ways of treating hepatitis. Recently, a lot of
attention has been focused on clinical trials involving pegylated
interferon.

How long does it take for a drug to be approved for human use? What
is a clinical trial? Where can I find information about ongoing
clinical trials for hepatitis treatment? These are just a few of
many questions related to clinical trials. Lets explore these and
other questions about clinical trials and gain an understanding of
just how the drug development process works.

Getting a new drug or treatment from the laboratory to people is a
long and methodical process. Long before a drug or treatment is made
available for human use, scientists spend many years of study and
discovery in the laboratory. If they believe it is a promising new
drug, it is tested in animals.

In the United States, after testing is completed in animals, a
company must then make application to the U.S. Food and Drug
Administration (FDA) in order to test it in humans. The FDA has
responsibility for determining whether a drug is safe enough to test
in humans. They have regulations and guidelines that must be
followed before, during, and after human testing. The FDA requires
proof of a products safety and effectiveness before they will
approve it for sale.

According to FDA, the average time of study and testing a new drug
before it is approved for use by the general public is eight and a
half years. That is an average; it can be a shorter time with
Accelerated Approval or take much longer. Some sources say 12 to 15
years. This long and complicated process is very expensive. Drug
companies spend an average of $359, 000,000 to develop a new drug,
according to FDA estimates. A worldwide company may spend as much as
$1 billion a year on research.

Information from the Pharmaceutical Research and Manufacturers of
America indicates only five out of 5, ooo compounds entering pre-
clinical testing make it to testing in humans. Of those five, only
one may be safe and effective enough to reach drug store shelves.
Results of well-controlled studies (clinical trials) must provide
good evidence that a new drug is effective and that the benefits
outweigh any risks.

PHASES of NEW DRUG DEVELOPMENT

Pre-clinical Phase

The first steps in searching for a new drug are limited to
laboratory test tubes. If a substance has shown promising effects in
test tube experiments, the next step is testing it in living
animals. Researchers need to find out what a drug does to the body
as well as what the body does to the drug. During animal testing the
scientists measure how much of a drug is absorbed into the blood
stream, how it is broken down chemically by the body, whether the
breakdown products are poisonous (toxic) to the body, and the time
it takes for the drug and its by-products to leave the body. If the
chemical has shown the desired effects and safety, the next step is
an application to FDA for testing in humans (Investigational New
Drug Application IND).

The FDA has regulations and guidelines to advise the drug companies
what kinds of results the FDA expects to see in any request for
human testing. If FDA determines that a product is effective and
safe enough to be tested in humans, then clinical trials can begin.

Clinical Trials

A clinical trial is a research study designed to answer detailed
questions about new treatments, diagnostic tests, screenings, and
disease prevention tested in people. Clinical trials may also be
called medical research, research studies, clinical study, and
clinical protocol. Protocol also refers to a set of rules upon which
a clinical trial is based. It describes who can take part in the
study, the length of the study, and the schedule for tests,
procedures, medications, and medicine dosages.

Participation in a clinical trial is strictly voluntary. A person
must give an informed consent in order to enter a study. The
researcher must make clear what the study involves, including risks
and possible benefits. It must also be made clear that the person
can leave the study at any time they wish. The rights and safety of
study participants (subjects) must be protected. A thorough
explanation of the study must be provided and all questions fully
answered. This must be done as a part of informed consent. Just
asking a person to be in a study and to sign a consent form is not
enough. Informed consent requires that the researcher conducting the
study do the following:

Give the subject adequate information about the study
Respond fully to the subjects questions and be certain that the
subject understands all the risks and responsibilities that are
entailed in participating in the study
Ensure that the subject is aware of other options, along with their
advantages and disadvantages
Obtain the subjects voluntary consent to take part in the study
Clinical Trial Phases

Clinical trials are divided into four phases. Each phase has a
specific purpose and a set of guidelines (protocol) or rules. The
protocol is based on what the study is trying to find out (study
design). It describes what characteristics the researchers are
looking for in their volunteer subjects. These may be such things as
age, type of disease, medical history, and current medical
condition. A person must qualify for the study based on the study
guidelines. The protocol states the things that allow a person to
join a study (inclusion criteria) and the things that keep a person
from participating (exclusion criteria). The purposes of criteria
are to identify suitable participants, keep participants safe, and
help make certain the researchers can answer the study questions.

Phase 1 the first use of a new drug in human studies. This phase
usually involves a small number of people, typically 20-80 healthy
volunteers. The purpose of this phase is to test the safety of a new
drug, how it works on the human body, to find the safe dosage range,
and determine if there are any side effects. Phase 1 can take a few
months or up to a year.

Phase 2 a further study of safety and to find out if the drug is
effective does it work as intended? Phase 2 studies usually involve
100-300 subjects who have the disease or condition the study is
seeking to treat, diagnose, or prevent. Phase 2 studies can take a
couple of years to complete.

Phase 3 a larger study taking more time and involving more people.
In this phase, hundreds or thousands of people may take part in an
expanded study of a drug or treatment. The new drug is usually
compared to current standard treatment. This study continues to
gather information about the safety and effectiveness of the study
drug or treatment over a longer time period. It watches for side
effects with long-term use. This phase lasts about 3 years.

At the end of Phase 3 testing, if a company determines the data
gathered show the drug to be safe and effective, a New Drug
Application (NDA) is made to FDA. All the information gathered about
the drug must be submitted in the NDA, which can be 100, 000 or more
pages in length. The FDA then has a team of reviewers evaluate all
the data. The FDA Center for Drug Evaluation and Research (CDER) is
responsible for approving new drugs. They look at drug safety and
effectiveness and risk vs. benefit. The FDAs final decision of
whether to approve a new drug for marketing is based on two main
questions:

Do the results of well-controlled studies provide substantial
evidence of effectiveness?
Do the results show the product is safe under the condition of use
in the proposed labeling? Safe, in this context, means that the
benefits of the drug appear to outweigh its risks.
If the review is favorable, the company is notified and the drug is
licensed by the FDA and can be produced and marketed. Drugs that are
found unsafe or not effective are not approved or licensed.

Phase 4 done after the drug or treatment has been approved and
marketed. These studies continue testing the study drug or treatment
to gather information about how it affects people in different
groups and any long-term side effects related to the drug. These
post-marketing studies may also include studies comparing the new
drug to other products and other uses for the new drug. FDA
continues to monitor drugs for safety even after they have been
approved for marketing (post marketing surveillance).

Questions to Ask Before Joining a Clinical Trial

The Centers for Disease Control and Prevention (CDC), National
Health Institutes, and FDA all address questions that people should
ask before entering a clinical trial. Before a person makes the
decision to enter a clinical study, they should make sure they
understand exactly what is involved and what is expected of them.
Some suggested questions to ask include the following:

What is the study about?
What is the purpose of the study?
Who is sponsoring, running, or in charge of the study?
What is required of me?
Will the study benefit me?
Will the study benefit others?
What are the risks involved?
How will I be protected from harm?
How will my privacy be protected?
What costs does the trial involve?
Who is responsible for any costs?
Will my insurance cover costs involved with the trial?
These are just a few of the questions that may be helpful in making
a decision to participate in a clinical trial. A person has the
right to have all their questions answered as a part of the informed
consent process.

Finding Clinical Trial Information

If you are interested in participating in a clinical trial, you can
ask your doctor, nurse, local hospital, health department, or
university for information about clinical trials being conducted
involving people with hepatitis. You can also do an online Web site
search for clinical trials. The Hepatitis Neighborhood has links to
the NIH Clinical Trials database and the Center Watch Clinical
Trials database located on the Members Welcome pageand on the New in
the News page.

More Information on Drug Development and Clinical Trials

The HepatitisNeighborhood Pharmacy Building -- New Drug Development:
Drug Development Process and Clinical Trials
NIH Clinical Studies Information 1-800-411-1222
http://www.cc.nih.gov
http://www.niaid.nih.gov
http://clinicaltrials.gov
http://clinicalstudies.info.nih.gov.gov


National Cancer Institute (NCI)

http://cancertrials.nci.nih.gov

The National Womens Health Information Center
http://www.4women.gov/faq/clinical.htm

Searle Pharmaceutical Company The Pipeline Game
http://www.searlehealthnet.com/pipeline.html

FDA/CDER 1-888-INFO-FDA
"From Test Tube to Patient:
Improving Health Through Human Drugs"
http://www.fda.gov/fdac/special/newdrug/ndd_toc.html

_______________

Sources:

Alliance Pharmaceutical Corp. (By Dale E. Wierenga, Ph.D. and C.
Robert Eaton,
Office of Research and DevelopmentPharmaceutical Manufacturers
Association). Phases of Product Development. [Online]. Available:
http://www.allp.com/drug_dev.htm (Accessed 7/12/00).

CDC, Divisions of HIV/AIDS Prevention. (1998). Taking Part in
Research Studies: What Questions Should You ASK? [Online].
Available: http://www.cdc.gov/hiv/pubs/brochure/unc3bro.htm
(Accessed 7/12/00).

FDA/CDER. (1999). From test Tube to Patient: Improving Health
Through Human Drugs. [Online]. Available:
http://www.fda.gov/fdac/special/newdrug/ndd_toc.html

National Cancer Institute (NCI), NIH. (1999) Cancer Trials:
Understanding Trials. [Online]. Available:
http://cancertrials.nci.nih.gov (Accessed 7/14/00).

NIH Clinical Center, Patient Recruitment and Public Liaison Office.
(2000). Clinical Research Studies at the National Institutes of
Health. [Online]. Available:
http://www.cc.nih.gov/ccc/prpl/info.html (Accessed 7/12/00).

NIH, National Library of Medicine (NLM). (2000). What is a Clinical
Trial? [Online]. Available:
http://clinicaltrials.gov/ct/gui/c/w1b/screen/PrintURL?
file=whatis.html&JServSessionIdcs_current=ri4txtqz3j (Accessed
7/14/00