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Animal Experimental Study
Animal Experimental Study
Animal Experimental Study
Outline
introduction (definition, history)
why doing AES
how to do AES
objects
animal model
sample size
ethical consideration
some examples
where to publish
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INTRODUCTION
definition
history
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what is AES?...
the use of non-human animals in experiments
although some research about animals involve only pure observation/
natural behavior
pure research: genetics, developmental biology, behavioral studies
applied research (experiment): biomedical research,
xenotransplantation, drug development, cosmetic testing
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terminology
animal experimental study (AES)
animal experimentation
animal research
animal model
animal testing
in vivo testing
vivisection
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history of AES
since 2nd 4th centuries BC
2nd-century: vivisection by Galen
12th-century: animal experimentation (surgery)
18th-century: discovery of drugs insulin, AB, vaccine
Laika (Sovyet dog); Dolly the sheep
20th-century: toxicology
1960s:
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as usual
Debatepro- & anti-animal testing
increasing of AE on animal controversy
ethical issue
harm (for animal) vs. potential benefit (for human)
animal protection law
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the need of
understanding of physiology, pathology, pathophysiology,
genetics of diseases
exploring and developing of new intervention (drugs, device,
etc.) of health problems
drugs:
ecacy (incl. pharmacokinetics, dose)
pharmacodynamics (mechanism of action)
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in general
1. Diseases process in human and animals have similarities
2. Cell systems contain or manipulate only a part of the
organ system.
3. Computer models lack the complexities of living entity
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HOW TO DO AES?
objects
animal model
sample size
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what animal?...
invertebrates vertebrates
non-human primates
50-100 million vertebrates/yr.
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invertebrates
fruit flies, worm
J short life cycle, ease with large numbers
L dierent immune system, simple organs
to identify active compound
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vertebrates
mice, rat, zebra fish, amphibians, cats, dogs, non-human primates
best model of inherited human disease
J genetic engineering model for a range of human disease
physiology, pharmacology, toxicology, cancer research, neurological
research, education J, endocrinology, reproduction, genetics,
HIV-AIDS drugs, vaccine, etc.
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Animal model
(of disease/condition)
to solve specific or practical problems
early stage of drug development
transgenic animal (inserted/modified/removed)
how and why disease develop?
test of new treatments
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ETHICAL
CONSIDERATION
e 3-Rs
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Reduction
Refinement
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how to do 3-Rs?...
Replacement
Reduction
Refinement
cell culture
experimental
techniques
less invasive
techniques
computer models
data analysis
better medical
care
human volunteers
sharing
information
better living
conditions
epidemiological
studies
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only after
animal is
unconscious
(anesthetized)
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EXPERIMENTAL
DESIGN
Basic principles
Sample size calculation
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...basic principles...
remember, this an
experimental study
1.
2.
3.
4.
5.
6.
RQ
comparison/control
replication
randomization
stratification
factorial experiment
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...basic principles...
1. RQ: does salted drinking
water aect BP in mice?
remember, this an
experimental study
1.
2.
3.
4.
5.
6.
Experiment:
RQ
comparison/control
replication
randomization
stratification
factorial experiment
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2. Comparison/control:
good experiments are comparative
compare BP in mice fed with salt water to BP in mice fed plain water
compare BP in strain A mice fed salt water to BP in strain B mice fed
salt water
3. Replication
will increase precision decrease the sample size J
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4. Randomization:
to avoid bias and to control the chance
RAL J
5. Stratification
replication measure BP in the morning and some in the
afternoon (limited by personnel)
dierent of BP between morning & afternoon measurement?
ensure that within each period: equal number of objects in
each treatment group
latertake account of the di. between periods in stat. analysis
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example
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example
RANDOMIZED
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example
STRATIFIED DESIGN
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6. Factorial experiments:
to assess eect of > 1 treatment/intervention
exp.: eect of both salt water & high-fat diet on the BP (2
intervention
ideally: look at all 4 treatments in one experiments (&
interactions among them)
plain water normal diet
x
salt water
high-fat diet
J we can learn more
more ecient
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AND..3-Rs reduction
variability
reduce number of treatment group, if possible
more homogenous object (i.e. in breeding, control other
variables- BW, age, sex, etc. if possible)
use stratification
multiple measurement more precise the mean of measurement
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Meads equation
E=NBT
Festing MFW, et al. Reducing the animal in lab BMR, ATLA, 1998
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E=NBT
Exp.
T = 3, B = 0 (10-20) =N-3
N = 13 23 5 7/group
N total: 15 21
Federers formula
T = 3 (t 1)* (n 1) > 15
2 * (n 1) > 15
n 1 > 15/2 (= 7.5 = 8)
n > 9 N total: 27
T (f.d) = 2x2x2 = 8
(10 20) = N (8)
N = 18 28 3/group
N total: 24
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Meads equation
N total: 15 - 21
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Pharmacodynamics study(1)
Route of administration:
Per Oral - similar to human use
Dose:
Based on Dose-Response Relationship
One or more doses that provide a desired eect
Dose conversion from human to animal may be used
Calculation of ED50
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Pharmacodynamics study(2)
Control group:
Negative control
Solvent / vehicle group
Positive control
Standard drug group
To validate that a method works
To obtain Relative Potency of drug candidate or herbal medicines
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Toxicological studies(1)
General toxicity test
Short-terms
Acute Toxicity Test (calculation of LD50)
Long-terms:
Sub Acute Test ( up to 1 month)
Sub Chronic Test ( up to 3 months)
Chronic Test ( up to 6 months)
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Toxicological studies(2)
Local toxicity test:
Dermatological Preparation
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disease
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disease
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disease
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disease
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WHERE TO PUBLISH?
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thank you
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