Download Preclinical Trials

If you had the power what
disease would you like to cure?
What do you think?

Have you ever had to take a medicine to
treat an illness?
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Have you ever wondered how researchers
determine if the medicines you take are safe
or not?
How drugs are discovered..
Engineers often find it easy to see the body
as a factory.
 Individual organs can be seen as machinery.
The actual nuts, bolts, screwdrivers, and
wrenches that make up all the machinery are
the equivalent of proteins, little chunks of
organic material that move things around in
the body and attach them together.
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Clinical Trials are the processes by which
scientists test drugs and devices to see if
they are SAFE and EFFECTIVE.
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.
Steps in Doing a
Pre-Clinical Trial:
Step One: Get an idea for a
drug target.
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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.
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.
How is Parkinson’s treated? Where should the
focus be?
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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.
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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
E
B
D
C
B
C
D
E
Any step in the pathway, for
example from A to B, or B to C,
might be a target for the right
drug.
*
See slide
note
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.

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!)
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.
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:
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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).
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?

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)
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)
Clinical Trials
Important for future therapies
http://www.bbc.co.uk/learningzo
ne/clips/human-drugtrials/1464.html
Definition
All clinical trials are prospective studies in
which individuals are exposed and
followed for an outcome
(or a few different outcomes).
The outcomes must be clearly defined.
What’s involved in a clinical
trial?
Forms need to be filed with the Internal
Review Board. A committee determines
whether the study is ethical.
2. Protocol. Before conducting a clinical trial, a
protocol must be written, describing exactly
what you are going to do
3. Trial - On site Patient Monitoring and Data
collection
4. Data analysis, write results and conclusions
5. Written report: includes clinical and
statistical sections
1.
The Placebo Effects
• “Inert” substitute for a treatment or
intervention.
• “Inert” means the compound has no
known activity that would be expected
to affect the outcome
•It must look exactly the same as the
tablet that you want to test!
Placebo Effects
In actuality, a placebo effect is a psychosomatic
effect brought about by relief of fears, anxiety or
stress because of study participation.
It's not just the little white pill that brings about
the effect; it's the additional attention and the
belief that your condition might be being treated
with a superior new treatment.
All outcomes affected by psychosomatics are
prone to placebo effects.
Blinding,
also called masking
If the outcome can conceivably be
affected by patient or investigator
expectations, then blinding is
important.
Types of Blinding
• Single Blind: The patient is ‘blind’
• Double Blind: The patient and the
investigator are ‘blind’
• Triple Blind: The patient, investigator
and data-cleanup people are ‘blind’.
(The statistician can only be partially
blinded since he/she has to know which
patients are in the same treatment
group.)