The purpose of any scientific research is to make predictions, hypothesize, ask questions and derive a deductive answer to a given question. Preclinical studies in animal employ pharmacokinetics, pharmacodynamics and toxicology for investigational product’s assessment with the intention to predict consequential outcome of the medicinal product’s safety and efficacy in human (Shank, Greek, & Greek, 2009). The predictive concept of pharmacodynamics deals with investigational product’s rate of absorption, distribution, metabolism, excretion and toxicology (ADME-Tox) (Glaser, 2007). The preclinical ADME-Tox model is essential in establishing most promising efficacy and pharmacokinetics in predicting dosage, synergistic, biological association, structural, conformational and specificity effects (Glaser, 2007).
However, the dilemma is that scientific hypothesis is a test conducted to compare what is expected to occur, to what actually occurs (Shank, et al., 2009). Therefore, pre-clinical trial in an animal model per se, defines what actually occurs as a stake to what happens in human studies. Thus, human studies result following the pre-clinical studies is expected to be in line with the predictive power of pre-clinical trial in an animal model. If that happens, the level of confidence and significance in human study’s safety is subject to the balance between the product’s risks and benefits (Shank, et al., 2009).
Perhaps, scientific prediction in human studies (clinical trial) is grounded in humans tendency to expect that similar outcome in preclinical trial is sequels to the proof of concept methodology model or the preclinical trials. Therefore, any deviation from this concept is not considered as a potent and robust concept. In addition, it is important to note that any modality that consistently fails to make accurate predictions is susceptible to mere coincidence; thus, the modality is not predictive simply because it sometimes forecast a correct answer (Shank, et al., 2009). Furthermore, it is imperative to understand the faulty thinking that exists in the animal-human study models in terms of the inherent divergence in biological pharmacodynamics, pharmacodynamics and toxicology mode of action between humans and animals, and not to mention the effects of the extrinsic factors and genetic predispositions (Glaser, 2007).
The inter-micro and macro genomic variation between animal and human may add enormous significance to the insignificant effects that frequently exists when 95% of experimental drugs are successful and efficacious in the animal preclinical trial phase, but then fails in the human clinical studies (Blackemore, & Langley, 2008). Nonetheless, in many cases micro-dosing technology, lethal dose (LD), toxic dose high (TDH) or maximally tolerated dose (MTD) applications in animal studies are used in grading the level of safety and efficacy of investigational products, which may or may not be considered safe in humans during the phase I studies via regression and inference studies (Clark, et al., 1999). On the other hand, even when investigational products are successful in both pre-clinical trial and human clinical studies, no medicinal product is completely safe from adverse events. Thus, the application of any approved drug should be administered with caution, applied for its intended use and most importantly, use according to the manufacturer’s directions.
References
Blackemore, C., & Langley, G. ( 2008). The animal experiment debate. The Vancouver Sun, p. B1. Retrieved from http://ezp.waldenulibrary. org/login?url=http://proquest.umi.com.ezp .waldenulibrary.org/pqdweb?did=1587131941&sid=1&Fmt=3&clientId=70192&RQT=309&VName=PQD.
Clark, D. L., Andrews, P. A., Smith, D. D., DeGeorge, J. J., Justice, R. L., & Beitz, J. G. (1999). Predictive value of preclinical toxicology studies for platinum anticancer drugs. Clinical Cancer Research, 5, 1161–1168. Retrieved from http://clincancerres.aacrjournals.org/ content/5/5/1161.full.
Glaser, V. (2007). Building better pipeline with ADME- Tox. Retrieved from http://www.gene ngnews.com/keywordsandtools/email/gen-articles/building-better- pipelines-with-adme-tox/12061/.
Dombey, S. & DeRenzo, E. (2012). Preclinical development
Mason, H. (2003, September 2). Americans, Britons at odds on animal testing. Gallup Poll Tuesday Briefing. Retrieved from http://search.ebscohost.com.ezp.waldenulibrary.org/l ogin.aspx?direct=true&db=bth&AN=11445119&site=bsi-live
Office of New Drugs in the Center for Drug Evaluation and Research (CDER). (2006). Guidance for industry, investigators, and reviewers: Exploratory IND studies. Retrieved from http://www .fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid ances/UCM078933.pdf
Shank, N., Greek, R., & Greek, J. (2009). Are animal models predictive for humans?. Philosophy, Ethics, and Humanities in Medicine, 4, 2 doi:10.1186/1747-5341-4-2. Retrieved from http://www.peh-med.com/content/4/1/2.
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