Animal Testing in Biomedical Research: An Annotated Bibliography and Literature Review

This annotated bibliography and literature review explores the ethical considerations, methodology, and translational value of animal testing in biomedical research. The review includes a range of studies that offer arguments from both sides of the debate, highlighting the undeniable value of animal testing in biomedical research, as well as the limitations and potential harms associated with the practice.

Assessment Part 1- Annotated Bibliography
Three articles were acquired after a thorough search of the PubMed database. During the search,
the records which were published between 2014 and 2019 were checked. A range of long and
short keywords were used during the search including ‘animal’, ‘animal testing’, ‘animal
research’, ‘animal experimentation’, ‘medical research’ and ‘biomedical research’. In addition,
Boolean operators (AND, OR) were also utilized during search to make different combinations
of search terms and make the search more productive.
Annotation 1
“Bara, M., & Joffe, A. R. (2014). The ethical dimension in published animal research in critical
care: the public face of science. Critical care, 18(1), R15.”
The quality of animal experimentations in terms of ethics is significant due to several reasons.
One of the reason is sustaining the support of public. The aim of the study is to ascertain the
stated consideration of the ethical aspects of Refinement, Reduction, and Replacement (3 Rs) in
critical care animal studies. The study revealed that reported, even if not essentially actual,
ethical quality of animal testing in three highly influential critical care journals was weak. The
study concluded that the clinicians, researchers, editors and reviewers, and funding bodies must
pay attention towards the ethical quality of the animal research. When these groups including
nurses will pay attention towards the 3Rs then only ethical quality of the animal research can
improve along with animal comfort, and the public support for animal testing (Bara & Joffe,
2014).
Annotation 2
“Merkow, J. S., Hoerauf, J. M., Moss, A. F., Brainard, J., Mayes, L. M., Fernandez-Bustamante,
A., ... & Bartels, K. (2018). Animal experimental research design in critical care. BMC medical
research methodology, 18(1), 71.”
The limitation of success in translation of animal models to human in critical care domain of
medicine is considered partly because of the insufficient or weak methodology, research design,
and recording in preclinical trials. The aim of the research is to draw comparison among
reporting of key characteristics of experimental rigor: blinding, randomization, and power

estimations in critical care animal testing. The study found that only a small section of
manuscripts which were published in journals of critical care field informed on proposed study
design steps to enhance rigor. Regular rationalization for the existence or lack of blinding,
randomization, and power estimations must be regarded to allow the public evaluation of likely
causes of bias in a better way (Merkow, et al., 2018).
Annotation 3
“Denayer, T., Stöhr, T., & Van Roy, M. (2014). Animal models in translational medicine:
Validation and prediction. New Horizons in Translational Medicine, 2(1), 5-11.”
The aim of the study is to discuss the recent issues and inadequacies of animal models by
focusing on fit-for-purpose validation. It is significant that the applied animal models are given
validation in concordance with the purpose based on a set of robust parameter and are also
reproducible. The preclinical animal testing of a drug is not a requirement by the regulatory
bodies for starting clinical trials, however, it offers useful data on the anticipated performance of
the drug clinically. Therefore, the study favored the animal testing by recommending it from
both business as well as patient perspective. The main focus of a nurse is working in accordance
with patient’s interests. Moreover, the translational worth of animal trials can be increased more
by combining it with developing alternative translational strategies (Denayer, et al., 2014).
Assessment Part 2- Literature review
In spite of huge resources invested in drug development, effectiveness of drugs at the time of
clinical development has remained minimal. One of the main rationale is erroneous preclinical
research, which requires utilization and result of animal models to fill the translational gap to the
practice. Animal models have a limitation of the capability in imitating the intricate processes of
pathogenesis, physiology of human beings. For example, it is found that overall percentage of
effective translation from animal models to clinical cancer experiments is below 8% (Mak, et
al., 2014). So, an argument is built that the identification of safety and efficacy in animal models
fails to be translated into human studies. Public and professionals from healthcare sector
including nurses consider the animal testing essential to forecast the safety and effectiveness of
drugs prior to evaluating them in clinical trials. But it is frequently found that the studies
frequently lag in during the research scrutiny and the 'predictive value' is non-significant.

A study enlisted the issues associated with animal testing. Problems root from several biases and
systemic failures which include bias and weak practice in methodology and analysis of data, no
transparency in empirical evaluation of the study, contradiction of flaws in cross-species
translation in the long-run, focus on profit rather than interest of patient and no liability of
expenses on animal experimentation. (Green, 2015).
On the other hand, other argument says that animal testing is reliable. Animals offer adequately
apt models of human biology and pathogenesis to give suitable data, and that, subsequently
delivers immense human health advantages. One of the study commented that scientific literature
which assesses the validity of animal experimentation usually induces significant issues
regarding its reliability and predictive value for findings in human beings and their physiology.
The inaccuracy of animal testing throughout an array of domains challenges the arguments
which favors its practice. Moreover, it is argued that animal testing frequently harms humans
substantially by fabricating safety trials and potential rejection of useful therapeutics. So, the
study concluded that consequent evidence indicates that the overall harms and costs to humans
from animal testing is more than the possible merits. It also suggested that resources should be
used in forming human related experimentation (Akhtar, 2015).
It is emphasized in literature that animal models are necessary to translate the drug outcomes.
Therefore, it is significant to critically assess the face and predictive validity of animal trials. It is
also indicated that the clinical bedside outcomes which were not estimated by animal trials must
be back translated and utilized to improve the animal trials. Suitable design, implementation and
recording of outcomes of animal models can assist in reproducing and translating the preclinical
data in practice in an easy manner. The scheme of the animal model technique is a part of the
translational project instead of a complete experiment. Data produced from animal models are
required to predict the clinical results for a particular drug which is being developed. It is
significant that the applied animal models are given validation in concordance with the purpose
based on a set of robust parameter and are also reproducible. The preclinical animal testing of a
drug is not a requirement by the regulatory bodies for starting clinical trials, however, it offers
useful data on the anticipated clinical performance of the drug. Therefore, the study favored the
animal testing by recommending it from both business as well as patient perspective (Denayer, et
al., 2014).

Another study found a variety of findings regarding translational success rates which suggests
that translational success is variable and cannot be predicted. So the study implicated that it is
not clear forthright that if the findings of primary animal testing will add to the translational
knowledge. The study address the need of comprehensive “umbrella”-researches of translational
success rates which are required to assess the probabilistic evidence to predict animal trials in
human scenario in a more reliable manner and also to ascertain the factors which impact this
process (Kouwenaar, et al., 2019).
It can be said that animal testing can contribute towards in vivo information, however, alternative
translational strategies have developed which have the potential of replacing the link between in
vitro trials and clinical practice. To advance the clinical translation, usage of human-based
mouse models and preclinical executions of clinical features can be observed. Development of
alternative translational approaches can increase the translational value of animal models by
combining them.
It is further suggested in literature that bias in animal trials must be addressed prior to biomedical
research so that decision-making in healthcare can be largely based on evidence. It is essential
that nursing practice is evidence-based. The likelihood of harm to patients and study participants
by relying on biased data gained through using animal model needs steps for improving its
operation, regulation and evaluation (Green, 2015).
A study suggested that since animal research has been the backbone of medical research, it is
essential that its translational value should be improved to the maximum. It can lead to
considerable scientific breakthroughs in finding diseases in human and improve healthcare. The
outcome of the research and its reproducibility can be improved by utilizing refined study
designs, having sample size which is statistically significant and ethically appropriate norms.
Other suitable approach in refining and reducing the animal number or trials is using systematic
reviews and meta-analyses for deducing the particular issues using the available literature and
their likelihood of efficacy in an animal model (Singh, et al., 2016).
Another study focused on the issues related to reporting of animal trials. It indicated that
numerous guidelines are present to improve reporting in articles. It particularly emphasized that
trials using animal models usually are often to demonstrate the significance of the findings and
therefore, smaller trials are pooled to enhance the rigor and offer more relevance to the

importance of the results (Baker, 2013). Therefore, smaller the sample size, the bigger the
random error is, consequently yielding more rigor to the research. Randomization and blinding
must be performed at the time of designing studies as if not done the effect size will be
miscalculated.
A study proposed that preclinical animal trials can never be completely valid because of the
ambiguities presented due to the species differences. It went on to say that even if several years
are spent in improving the validity of animal testing, the clinical significance of the animal
models will ultimately only improve to a certain degree. It is due to the differences in species
which will keep on making translation from animals to humans invalid. The study suggested that
to improve clinical translation and at the end help patients, experiments must focus on human-
based research methods and techniques (Pound & Ritskes-Hoitinga, 2018). The alternatives to
animal trials help in lowering the number of animals needed for research up to a degree but they
are unable to completely eradicate the requirement of animals in experiments.
So, it can be concluded that in the literature review, studies offered arguments from both sides. A
range of studies indicated towards the undeniable value of animal test in biomedical research
which eventually helps in clinical trials. On the other hand, other studies raised question on the
translational success of the animal models to humans as the preclinical animal trials fail to be
completely valid due to the ambiguities presented due to the species differences.
References
Akhtar, A., 2015. The Flaws and Human Harms of Animal Experimentation. Camb Q Healthc
Ethics, 24(4), pp. 407-419.
Baker, M., 2013. Neuroscience: Through the eyes of a mouse. Nature, 502(7470), pp. 156-8.
Bara, M. & Joffe, A. R., 2014. The ethical dimension in published animal research in critical
care: the public face of science. Crit Care, 18(1), p. R15.
Denayer, T., Stöhr, T. & Roy, M. V., 2014. Animal models in translational medicine: Validation
and prediction. New Horizons in Translational Medicine, 2(1), pp. 5-11.

Green, S. B., 2015. Can animal data translate to innovations necessary for a new era of patient-
centred and individualised healthcare? Bias in preclinical animal research. BMC Med Ethics,
16(1), p. 53.
Kouwenaar, C. et al., 2019. Animal to human translation: a systematic scoping review of
reported concordance rates. J Transl Med., 17(1), p. 223.
Mak, I. W., Evaniew, N. & Ghert, M., 2014. Lost in translation: animal models and clinical trials
in cancer treatment. Am J Transl Res, 6(2), pp. 114-118.
Merkow, J. S. et al., 2018. Animal experimental research design in critical care. BMC Med Res
Methodol, 18(1), p. 71.
Pound, P. & Ritskes-Hoitinga, M., 2018. Is it possible to overcome issues of external validity in
preclinical animal research? Why most animal models are bound to fail. Journal of Translational
Medicinevolume, Volume 16.
Singh, V. P. et al., 2016. Critical evaluation of challenges and future use of animals in
experimentation for biomedical research. Int J Immunopathol Pharmacol., 29(4), pp. 551-561.