Errors in animal experiments

1. UNVEILING THE
COMPLEXITY:
UNDERSTANDING ERRORS IN
ANIMAL EXPERIMENTATION
By
Sachin Nayak
22PCM3636

2. • What is an ERROR ?

3. INTRODUCTION
• Statista, a global data portal for market and economic sector statistics, estimates
the global markets for animal testing in 2018 at $7.4 billion for drug discovery,
$11.2 billion for preclinical develop ment and safety, $58.5 billion for clinical
develop ment, and $2.3 billion for central laboratory testing
• Understanding errors is crucial to -
* Improving Safety
* Enhancing Performance
* Preventing Recurrence
* Increasing Reliability
* Optimizing Training Programs
* Compliance with Regulations
Animals
used in
scientific
research
and
experimenta
tion
To gain
insights into
various
biological
and medical
processes
To test the
safety and
efficacy of
new drugs
Toxicity
testing
vaccine
developm
ent etc…..
It is estimated that more
than 192
million animals
worldwide are used in
laboratory experiments
every year

4. TYPES OF HUMAN ERRORS IN ANIMAL EXPERIMENT AND ITS
CAUSE
• Experimental Design Errors :Inadequately controlled variables or flawed study protocols, can impact the validity of the results,
introduce bias into the study
• Data Collection Errors :Inaccuracies in recording data, measurements, or observations can compromise the integrity of the study.
• Procedural Errors : Lack of precision in handling animals, administration of substances, or timing of experiments can introduce
variability.
• Ethical Compliance Error :Improper animal housing, insufficient veterinary care, or neglect of principles such as the Three Rs
(Replacement, Reduction, Refinement) in animal research
• Sample Handling Errors:
• Communication Errors:
• Equipment and Instrumentation Errors:
• Record-Keeping Errors:.
• Training and Skill Errors:
Inadequate training
Excessive work load and time pressure
Insufficient funding and resources
Equipments and fascilities availability
CAUSE

5. IMPACT OF ERRORS ON ANIMAL EXPERIMENT
Data Accuracy
and
Interpretation -
Compromise the
accuracy of results
leads to incorrect
conclusion
Animal -
Unnecessary
stress,
discomfort, or
harm to the
animals
Resource
Wastage-Wastage
of valuable
resources, including
time, money, and
animal lives
Public Perception
and Trust-High-
profile cases of
human errors in
animal experiments
can erode public trust
in scientific research.
Scientific Integrity-
Incorrectly conducted
experiments may contribute to
the dissemination of flawed
information, impacting
subsequent research and
potentially leading to the
development of ineffective or
unsafe treatments

6. IDENTIFYING AND PREVENTING HUMAN ERRORS IN
ANIMAL EXPERIMENT
Comprehensive Training and clear guidance:
Clear Protocols and Standard Operating Procedures (SOPs)
Team Communication:
Encourage a culture of open communication within the research team
Reporting and Learning from Errors:
Regular Reviews of Protocols:
Periodically review and update experimental protocols in light of new
information, technological advancements, or changes in regulations.

7. SOME FACTS THAT NEED AN ATTENTION
More than 90% of basic scientific discoveries, most of which are from experiments on animals, fail to lead to human
treatments
Eighty-nine percent of preclinical studies, most of which involve animals, could not be reproduced.
NIH admits that 95% of all drugs that are shown to be safe and effective in tests on animals fail in human trials because
they don’t work or are dangerous
A 2009 survey found that mice and rats used in invasive, painful surgeries were provided with post-operative pain relief
only about 20% of the time.
PPV between mouse and rat is around 50%,which is no greater than random chance
Overall, approximately 89% of novel drugs fail human clinical trials, with approximately one-half of those failures due to
unanticipated human toxicity ,If animal tests accurately predict human toxicity, then why are toxicity-related failure rates
in human clin ical trials so high?
In emergency cases FDA may approve drug for human use based solely on animal testing

8. Penicillin (Fatal
to guineapigs)
Paracetamol(To
xic to dogs and
cats)
Aspirin(Embry
otoxicity in rats
and rhesus
monkeys)
Morphine
(Hyperexciteme
nt in cat but
calming effect
in human)
Four years
delay in
ganciclovir
approval (bcz
of lack of
animal testing)
Gleevec-
Chronic
myelogenous
leukemia
(CML)- Serious
adverse effects
in animals but
not on human
cell assays
Aripiprazole
(Abilify) and
esomeprazole
(Nexium),
showed low
oral
bioavailability
in animals
CASE STUDIES
Van Norman, Gail A. "Limitations of animal studies for predicting toxicity in clinical trials: is it time to rethink our current approach?." JACC: Basic to Translational Science 4, no. 7 (2019): 845-854.

9. CASE STUDIES
Vioxx(Merck) after
approval caused
CVS morbidity and
motality along with
38000 died and 9
billion settlement
Isuprel
(asthma)cause 3500
death in UK
(despite safe in
rat,dog,monkey,gui
nea pig)
Thalidomide –
Phocomelia -20000-
30000
infaints(although
tested in 10 strains
of rat,11 breeds of
rabbit,2 breeds of
dog,3 strains of
hamster,8 species of
primates)
Fialuridine for
hepatitis B –Death
of healthy
volunteers even safe
in animals
Pfizer (Lipitor) –No
promising effect in
animal experiment
but effective in
humans

10. GROWING SCIENTIFIC CRITICISM
• In 1962 Lichtfield examined 6 drugs studied in animal models and opined that -
“The differences between species in specific drug responses were so striking that one could actually use the results of
drug toxicity tests alone to identify whether an entity was a rat, rather than a dog or a man, and concluded there was no
basis for predicting adverse human effects for the 6 drugs from animal studies.”
• In 1981 “Council on scientific affairs of Americal medical association” stated-
“Carcinogenicity in animal tests does not predict risk in human experiments”
• In 2019 “West coast regional safety pharmacology safety meeting” stated
“lack of concordance between animal and human safety studies , nervous system,CVS,respiratory system”…….
Akhtar, Aysha. "The flaws and human harms of animal experimentation." Cambridge Quarterly of Healthcare Ethics 24, no. 4 (2015): 407-419.

11. REASON BEHIND THE FAILURE
The effects of the
laboratory environment
and other variables on
study out comes
Disparities between
animal models of
disease and human
diseases
Species differences
in physiology and
genetics
• Cortisone levels rise in monkeys
watching other monkeys being
restrained for blood collection.
• Blood pressure and heart rates elevate in
rats watching other rats being
decapitated,
• Stressed rats, develop chronic
inflammatory conditions and intestinal
leakage, which add variables that can
confound data)

12. AN APPOROACH TO OVERCOME THIS FAILURES
• Genetically modified (GM) animals, including transgenic mice models, wherein human genes are inserted into the
mouse genome. However, if a human gene is expressed in mice, it will likely function differently from the way it functions in
humans, being affected by physiological mechanisms that are unique in mice.
{Example, a crucial protein that controls blood sugar in humans is missing in mice. When the human gene that makes this
protein was expressed in genetically altered mice, it had the opposite effect from that in humans: it caused loss of blood sugar
control in mice}
• Nonhuman primates (NHPs) models have failed to reproduce key features of Parkinson’s disease, both in function and in
pathology
• HIV/AIDS vaccine research using NHPs represents one of the most notable failures in animal experimentation translation.
[All of about 90 HIV vaccines that succeeded in animals failed in humans]
Gp120 failed to neutralize HIV grown and tested in cell culture,however, because the serum protected chimpanzees from HIV
infection, two Phase 3 clinical trials were undertaken —a clear example of how expectations that NHP data are more
predictive than data from.

13. ALTERNATIVES TO ANIMAL EXPERIMENTATION
Cells and tissue cultures, alternative organisms, lower vertebrates, invertebrates, CAL, CADD, animal free
recombinant antibodies, drug repurposing(cheaper as compared to development of new chemical entity)
Van Norman, Gail A. "Limitations of animal studies for predicting toxicity in clinical trials: Part 2: Potential alternatives to the use of animals in preclinical trials." Basic to Translational Science 5, no. 4 (2020): 387-
397.

15. Most of the major breakthrough in medicine resulted from animal experimentation
• The concepts of heart and its connection with large arteries and veins only got attention when Harvey(1671) investigate in living animals
• Von haller discovered how nerves make muscle contract
• Galvani proved electrical coupling of neuromuscular junction