The document describes the process of pre-clinical trials for testing new drugs. It involves: 1) Identifying a drug target through basic research and applying that knowledge through applied research. 2) Developing a bioassay, usually using animal or cell models, to test the drug's safety and effectiveness. 3) Establishing the effective and toxic doses of the drug through screening in the bioassay system. 4) Filing for approval as an Investigational New Drug with the FDA if results show promise, allowing tests in human clinical trials. The goal of pre-clinical trials is to determine if a new drug or medical device is safe and effective before testing in humans using the scientific method.

1. The Application of the
Scientific Method:
Preclinical Trials
Copyright 2010. PEER.tamu.edu

2. What do you think?
 Have you ever had to take a medicine to
treat an illness?
 Have you ever wondered how researchers
determine if the medicines you take are safe
or not?

3.  Pre-Clinical Trials and Clinical Trials are the
processes by which scientists test drugs and
devices to see if they are SAFE and
EFFECTIVE.

4. What is a Preclinical Trial?
 Preclinical trial - a laboratory test of a new
drug or a new medical device, usually done
on animal subjects, to see if the hoped-for
treatment really works and if it is safe to test
on humans.

5. There are two types of Research:
Basic and Applied
Basic Research: discovering new facts about how
things work, how they are made, or what causes a
biological event to occur. Basic research can
explore a topic, explain a topic or describe a topic.
For Example: A researcher discovered that genes
can be turned off or on by small RNA molecules in
the body. This study was conducted on worms. It
led to the Nobel Prize in 2006.

6. “Basic” vs. “Applied”
Research
Applied Research: Taking the
information discovered in basic
research and investigating how to
use it to treat and prevent
sicknesses.
Example: A researcher uses the
information about turning genes Segment of DNA.
off and on to find a drug that is Many such
segments act as
used to turn off genes that cause genes.
diseases and disorders in humans.

7. Where Do We Get New Ideas For
Research?
Ideas come from all kinds of scientists and medical
professionals who do research in universities, government
labs, and in corporations.

8. Take a Minute to Discuss:
 What is a Pre-Clinical Trial?
 What is the difference between basic
research and applied research?
 What sickness or disease would you like to
see an effective treatment for?

9. There are several steps involved
with doing a Pre-Clinical Trial:
File for approval as an Investigational New
5 Drug (IND)
4
Establish Effective and Toxic Doses
Screen the Drug in the Assay
3
Develop a Bioassay
2
Indentify a Drug Target
1

10. Steps in Doing a
Pre-Clinical Trial:
Step One: Get an idea for a
drug target.
 Drugs usually act on either cellular or genetic
chemicals in the body, known as targets,
which are believed to be associated with disease.
 Scientists use a variety of techniques to identify
and isolate individual targets to learn more about
their functions and how they influence disease.
 Compounds are then identified that have various
interactions with the drug targets that might be
helpful in treatment of a specific disease.

11. Finding the Right Target Is Not Easy
Parkinson’s Disease Example:
Parkinson's disease:
a disease which causes
deterioration of the
central nervous system
over a period of time.
This disease often
impairs the patient’s
movement, speech, and
other functions.

12. How is Parkinson’s treated? Where should the
focus be?
 Tremors or shaking occurs when cells in one part of brain die. These
cells communicate using a chemical called dopamine.
 Drugs that replace dopamine work only for a few years.
 Other Parkinson’s symptoms (depression, sleep disorder, digestive
problems, loss of brain function) have other causes.
 Another sign of Parkinson’s disease: many cells have deposits of a
protein, synuclein.
 Four drug companies are developing drugs to counter synuclein,
even though nobody knows if it is a cause or a consequence of
Parkinson’s.
 Synuclein could be like a tombstone—a marker, not a cause of cell
death.

13.  Drugs target specific points in biochemical pathways
 Biochemical pathways are series of chemical
reactions occurring within a cell. In each pathway, a
principal chemical is modified by chemical reactions.
 Examples of different types of biochemical pathways:
A
A B C D E
E B
Any step in the pathway, for
example from A to B, or B to C,
might be a target for the right
D C
drug.
* See slide
note

14. Steps in Doing a
Pre-Clinical Trial:
Step Two: Develop a Bioassay
A Bioassay is a “live” system that can be
used to measure drug effect.
 It may be a culture of cells or
organs or a whole animal.
For example:
 Zebra-fish embryos - you
can see effects of drugs on
bone density, blood vessel
growth and many other
systems of the zebra-fish.

15. Steps in Doing a
Pre-Clinical Trial:
Step Three: Screen the
drug in the Bioassay.
 This is the actual test of the
drug on the chosen bioassay.
 This will determine if the drug
is SAFE and if it is EFFECTIVE
in the bioassay (BEFORE it is
ever tested on humans!)

16. Steps in Doing a
Pre-Clinical Trial:
Step Four: Establish what dosage
amount of the drug is safe and what
dosage amount of the drug is toxic.
 Most drugs have a toxic level or an amount at
which the drug will become
harmful instead of helpful.

17. Steps in Doing a
Pre-Clinical Trial:
Step Five: Application is made to the
Food and Drug Administration (FDA)
as an Investigational New Drug (IND).
IND must show how the drug:
 Is manufactured.
 Appears (color, solubility, melting point,
particle size, moisture content).
 Formulated (pills, liquid, etc. + inactive ingredients).
 Will be analyzed for purity, concentration, stability.
 Will be tested for safety (this will be the basis for
allowing first use in humans).

18. Think Break:
 How are these steps like the steps of the
Scientific Method?
 Why would research scientists use a
Bioassay instead of a human subject to
test a new drug?
 What percentage of drugs do you think get
this far in the process?

19. Review: Steps to New Drug Discovery
Pre-Clinical Trials
Get idea for drug target
Develop a bioassay
Screen chemical compounds in assay
Establish effective and toxic amounts
File for approval as an Investigational
New Drug (IND) (leads to clinical trials)

20. Can you summarize the
process?
With a partner or your group, write a summary of
the Pre-Clinical Trial Process. Use the following
words to help you:
Drug
Safe
Effective
Basic Research
Applied Research
Target
Biochemical Pathway
Bioassay
Toxic
Investigational New Drug (IND)

21. Pre-clinical Research
at
Texas A&M
College of Veterinary
Medicine and
Biomedical Sciences