Response to the following discussion posts. Each question needs to be at least 2 paragraphs with a 7 sentence minimum per paragraph. This also needs to be in APA 7th edition format and at least 2 references per response.
- Compare 3 elements (of your choosing) for ethical human research to the various rules (Blue Book) and protections for research animals – are they the same, what makes them different?
- Animal research is controversial, using your knowledge of human subject research and your knowledge of animal research, state, and defend your opinion of current rules and protections making sure to include the 3 Rs (Replacement, Reduction, Refinement).
Animal research or pre-clinical studies are conducted on animals to provide adequate information on a particular drugs potency, safety, and effectiveness. As stated by (Polson & Fuji, 2012), the ultimate goals of preclinical studies are to predict the desired biological effect of a drug and to identify and characterize all toxicities associated with it for informed risk assessment. However, these animals have rights and needed to be protected from unnecessary harm and discomfort. The Animal and Plant Health Inspection Service (APHIS) is the agency within the USDA responsible for enforcing the Animal Welfare Act (AWA) which requires that minimum standards of care and treatment be provided for animals bred for commercial sale (Animal Welfare Act | National Agricultural Library, n.d.). APHIS has published the Blue Book, as a tool to improve compliance with the application of the animal protection rules.
- Social Value: In ethical human research studies must impose social value. That is the research must improve human health either by generating generalizable knowledge for better understanding or by offering new treatments for diseases. So, its unethical to put people at risk of harm or discomfort when society and humans cant benefit. The same goes with animal research, the guidance by AWA clarified that the design and performance of procedures performed on animals should be based on relevance to human or animal health, advancement of knowledge, or the good of society. Insights into diseases such as COVID-19, Diabetes, and Cancer contributed to the similarity in biological makeup between humans and some animals (Why Animal Research?, n.d.). So, animal research is important to be able to start clinical studies that are significant for human health. However, animals shouldnt experience pain, discomfort, or harm for no reason and should be protected. (Animal Welfare Act | National Agricultural Library, n.d.; Animals, 2011; Dept, 2017; National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals, 2009)
- Independent Review: In human ethical research, an independent review by unaffiliated individuals with no multiple interests assures the implementation of the ethical principles in the research. Independent review of a study assures members of society that people who enroll in trials will be treated ethically and the risk-benefit ratio is favorable and considerably reviewed. Independent review in animal research was considered by AWA, and the Institutional Animal Care and Use Committee (IACUC) are qualified members of experience to oversee the institution’s animal program, facilities, and procedures. The IACUC periodically reviews the institution’s program for humane care and use of animals, using the Guide as a basis for evaluation, an inspection of animal facilities in the institution, and preparing reports of compliance. The committee has the authority to review, approve, require modifications, or suspend any unethical activities (Animal Welfare Act | National Agricultural Library, n.d.; Online Survey Software | Qualtrics Survey Solutions, n.d.; Animals, 2011; Dept, 2017).
- Favorable Risk-Benefit Ratio: Any research has risks, but these risks must be balanced by the benefits to the subjects or our society. In ethical clinical research, minimizing the risks and burdens as much as possible is more favorable and preferable. But, if the risk of the research increases, the benefits gained from it must increase as well. Researchers should always be very careful to minimize risk and protect subjects. The first step taken in the protection of animals from burdens in the research is the consideration of alternatives like in vitro systems, computer simulations, and/or mathematical models to reduce or replace the use of animals thus minimizing the researchs risks. PHS Policy stated that Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. This second step indicates the concerns of the regulations and rules to minimize the burdens on the research animals. Additionally, in CFR, Title 9, Chapter 1, Subchapter A, a statement described that the principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain. The use of appropriate sedation, analgesia, anesthesia, and adequate veterinary care is another step taken to minimize the risks and obtain a favorable risk-benefit ratio in animal research (Animals, 2011; Dept, 2017; Online Survey Software | Qualtrics Survey Solutions, n.d.).
There will always be differences and controversies between the regulations of human research and the law and guidance of animal research. Humans are in control of animal research, regulations, and rules, they can control animals. Animals are considered vulnerable and cant express themselves, suffer, and pain. They can be easily exploited by organizations or researchers that are not registered in the institutions governing the animals rights. Humans still can talk and express what they want and feel. Informed consent in human research governs their rights and plays a major role in the law and court, this is not the case in animal research. Also, human research regulations evolved many years ago and still till now are experiencing amendments. Animal regulations will take time to be correctly and globally comprehended and implemented. Time is needed to practice animal research regulations to address the missing parts and points and find solutions and ways to find them. The milestone journey toward research animal protection began and it started since 1960 when Russel and Burch in their book The Principle of Humane Experimental Technique discussed the 3 Rs stand for Replacement, Reduction, and Refinement. Replacement alternatives are methods that avoid or replace the use of animals. This includes both absolute replacements such as replacing animals with computer models and relative replacements (replacing vertebrates, with animals having a lower potential for pain perception, such as some invertebrates). Reduction alternatives are like any strategy that will result in fewer animals being used to obtain sufficient data to answer the research question thus potentially limiting or avoiding the subsequent use of additional animals, without compromising animal welfare. Refinement alternatives refer to the modification of husbandry or experimental procedures to minimize pain and distress and to enhance the welfare of an animal used in science from the time it is born until its death (Hubrecht & Carter, 2019). Animal research regulations consist of rules, guidance, and principles trying to minimize the harm and burden on these animals, but there will be a difference between these regulations and human research regulations.
Animal Welfare Act | National Agricultural Library. (n.d.). Retrieved August 22, 2022, from https://www.nal.usda.gov/animal-health-and-welfare…
Animals, N. R. C. (US) C. for the U. of the G. for the C. and U. of L. (2011). Animal Care and Use Program. In Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK54045/
Dept, A. (Ed.). (2017). USDA Animal Care: Animal Welfare Act and Animal Welfare Regulations. United States Department of Agriculture.
Hubrecht, R. C., & Carter, E. (2019). The 3Rs and Humane Experimental Technique: Implementing Change. Animals : An Open Access Journal from MDPI, 9(10), 754. https://doi.org/10.3390/ani9100754
National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals. (2009). Recognition and Alleviation of Pain in Laboratory Animals. National Academies Press (US). http://www.ncbi.nlm.nih.gov/books/NBK32658/
Online Survey Software | Qualtrics Survey Solutions. (n.d.). Retrieved August 22, 2022, from https://nihodoercomm.az1.qualtrics.com/jfe/form/SV…
Polson, A. G., & Fuji, R. N. (2012). The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients. British Journal of Pharmacology, 166(5), 16001602. https://doi.org/10.1111/j.1476-5381.2012.01916.x
Why Animal Research? (n.d.). Retrieved August 22, 2022, from https://www.nabr.org/
One ethical principle that appears to be similar between human research and animal research is that there should be a favorable risk-benefit ratio. Emmanuel et al. describes that in order for research to be ethical, the risks and benefits must be equally weighed (Emanuel et al., 2016). This may be done by minimizing the risks to the research subject and enhancing the benefits available to the research subject and the society and then assessing the situation to assure the risks do not outweigh the benefits (Emmanuel et al., 2020). There may even be a favorable risk-benefit ratio where the subject does not benefit from participation. An example of this may be a survey which is low risk and may offer a great benefit to society. As for animal research, there seems to be a risk-benefit ratio required, although it does not necessarily have to be beneficial for the animals which are part of the research. The animal welfare act in the blue book, specifically 9 CFR 2.31, outlines certain requirements for reduced harm to the animal during research (United States Department of Agriculture, 2019). It describes that research will minimize the amount of pain the animals are subjected to, that alternatives that would produce less pain have been considered, no animal will be used in more than one major operative surgery, etc. With all of this being said, the main difference is that there must be a favorable risk-benefit ratio for human research, while with animal research it seems that the risk-benefit ratio must only be optimized. With animals, there are oftentimes going to be risks that may outweigh the benefits, but it is important to reduce the risks as much as possible.
Another ethical principle which holds some similarities between human and animal research is independent review. In animal research there is the IACUC and in human research there are various types of review boards which oversee the approval and process of the research. The blue book states that at least one member of the IACUC must not be affiliated with the facility other than as a member of the board (United States Department of Agriculture, 2019). This is similar to IRBs which require at least one member to be in no way affiliated with the facility. Overall, maintaining an independent review helps ensure the ethical treatment of both human and animal research subjects.
One ethical principle that is not similar between human and animal research is informed consent. The blue book does not mention informed consent, most likely because animals dont have proper decision making capacity as compared to humans. Informed consent is arguably one of the most integral parts of human research and can be found in numerous regulations and ethical documents.
I believe that the current rules and regulations regarding animal research are mostly adequate. In my opinion, I think that it must be understood that unfortunately animal research is a sort of necessary evil when it comes to advancing science and the wellbeing of humanity. If these trials were not done on animals, they would have to be done in humans and that would most likely pose an enormous risk to the human population. The three Rs (replacement, reduction, and refinement) aid this process by minimizing the amount of pain that research animals are subjected to (Animal Use Alternatives, n.d.). With advancing technology and research practices, it should continue to be easier to implement the three Rs. For example, with better computer models and in-vitro technologies, animals can be replaced in research at a greater rate. With better experimental design and statistical analysis, the number of animals used in research may be reduced. Finally, with different anesthetics, and different humane methods, the care of the animals may be refined and their wellbeing ultimately improved (Animal Use Alternatives, n.d.).
With all of that being said, one aspect of animal research I do not agree with is the fact that all animals are not afforded the same protections as one another. In the blue book, the definition of an animal specifically excludes rats, mice and birds bred for research (United States Department of Agriculture, 2019). This indicates that mice, rats and birds do not have any legal protections in research under the animal welfare act and regulations. I personally believe that if some animals can be given rights, then all animals should be given those same rights. Ultimately, I believe most of the regulations in place along with the three Rs are great, but they dont serve much of a use if they cannot be applied to certain animals such as rats, mice and birds. This is especially true when rats, mice and birds account for an estimated 95% of all animals in research (Smith, 2002).
Animal Use Alternatives (3Rs).| National Agricultural Library. (n.d.). Retrieved August 23, 2022, from https://www.nal.usda.gov/animal-health-and-welfare/animal-use-alternatives#:~:text=The%20%E2%80%9C3Rs%20alternatives%E2%80%9D%20refers%20to,Principles%20of%20Humane%20Experimental%20Technique%22.
Emanuel, E.J., Abdoler, E., & Stunkel, L. (2016). Research ethics: How to treat people who participate in research.
Emanuel, E. J., Wendler, D., & Grady, C. (2000). What makes clinical research ethical?. JAMA, 283(20), 27012711. https://doi.org/10.1001/jama.283.20.2701
Smith, D. (2002, July). Rats, mice and birds excluded from Animal Welfare Act. Monitor on Psychology, 33(7). https://www.apa.org/monitor/julaug02/rats
United States Department of Agriculture. (2019). Usda Animal Care: Animal Welfare Act and Animal Welfare Regulations.
The social value of clinical research can be evaluated from different perspectives in human research. The simple view of social value for clinical research is in the knowledge it generates about disease, disease process and the improvements to health that truly give it value. In human research, social value can also be seen on different types of value, such as progressive value, which indicates a clinical trial will go on to the next stage; or to humanitarian value of clinical trials, meaning the clinical trial can result in broader terms of more immediate results like improved healthcare outcomes. The sole purpose and tenant of gaining knowledge through clinical research, we should not expose humans to potential harm. The final justification of humans in research is linked to the anticipated social value of the intervention itself. (Habets, , et al. 2014).
In 2004, The FDA estimated that 92% of drugs that pass pre-clinical test using animals fail to make it to market. More recent analysis demonstrates that despite efforts to improve the predictability in animal testing, the failure rate may be as high at 96%. The article sites a failure of lack of effectiveness and safety problems that were not predicted by animal testing (Beauchamp, DeGrazia 2015)
If we consider the Animal Welfare Act at face value, The ruling specifies protection for animals and the various classes of animal protections such as the humane standards for humane handling, care, treatment and transport of animals. but the standard does not address the social value of the animal and their contribution to improved health or healthcare itself.
Fair Subject Selection refers to who the study needs to include for the problem they are trying to solve. People, like animals should be chosen for a study in a way that would minimize harm and enhances the benefit for the individual or animal. The difference for humans and animals in this situation is the person can accept the risk and burden of research and can possibly enjoy the benefits where as the animal can not consent nor accept or refuse risk. Although there are specific standards in the Blue Book for Animal Welfare Act and Animal Welfare Regulations, for the protection and humane handling of animals for research that cover record keeping by dealers, research facilities, handlers and carriers, but the AWA does not discuss vulnerable subjects or protected species.
Respect for potential and enrolled subjects refers to persons entering a clinical trial or study from the initial encounter with the principal or sponsor representative to discuss the enrollment decisions or a discussion about aborting the trial. It is obvious animals do not have the capacity for this kind of exchange. Standard 2143 (Standards and certification process for human handling, care, treatment and transportation of animals. Animal Welfare Act and Animal Welfare Regulation). Respect for animal care is in this segment and includes their care, treatment and practices in experimental procedures to ensure the animals pain and distress are minimal including adequate veterinary care with the appropriate use of anesthetic, analgesic, tranquilizing drugs. I found a little comfort in that no animal is used in more than one major operative experiment from which it is allowed to recover. (Animal Welfare Act and Animal Welfare Regulations).
Personally, I grew up on a large farm in Virginia/Tennessee (state line) where my family has raised cattle for 150 years. I grew up with respect for animals not just as providers of meat, milk and other value added products (the cornerstone of the country girl diet: butter, cheese and eggs!). Some animals were like family members, so it is hard for me to justify research on animals as a preliminary course for evaluating the value for moving from animal to human research.
When I examine the 3 Rs (Replacement, Reduction and Refinement) as guiding principles, I go back to the current focus on animal welfare, the 3Rs lack an important ethical dimension that says research on animals in only ethical if generates value for science and society. This is not a tenant of the 3 Rs currently (Strech, Dirnagl 2019). There is significant publication bias for clinical research where null or negative results end up in a trash can or file drawer and often do not have a reliable study design. There is an argument that the current Animal Welfare Act lacks practice oriented guidelines promoting scientific value. Robustness, Registration and Reporting are principles that are more favorable in theory but have not been put in practice. One reason is the difficulty implementing robustness but certainly registration and reporting are much more attainable goals. Robustness is difficult to measure and I’m not certain of where you would begin.
A animal registry and reporting measures can be set up using tools like ClinicalTrials.gov. After reading the article on the 3 Rs, I can appreciate the concept of complementing the current 3 R system with a second set for scientific value. (Strech, et al)
Habets, GJL. Michelle., Van Delden, Johannes, JM., Bredenoord, Annelien. (2014, September 5). BMC
Medical Ethics. The Social Value of Clinical Research.
Beauchamp, L., Tom, Degrazia, David. (2015, October 24, 2015). The Flaws and Human Harms of
Animal Experimentation. Campridge Qualrterly of Healthcare Ethics.
Animal Welfare Act and Animal Welfare Regulations. US. Department of Agriculture. (2022 May)
Strech, Daniel., Dirnagl, Ulrich. 2019. BMJ Open Science. 3Rs missing; animal research without
scientific value is unethical. https://openscience.bmj.com/content/bmjos/3/1/bmjos-2018-