Can animal data translate to innovations necessary for a new era of patient-centred and individualised healthcare? Bias in preclinical animal research

Abstract

BackgroundThe public and healthcare workers have a high expectation of animal research which they perceive as necessary to predict the safety and efficacy of drugs before testing in clinical trials. However, the expectation is not always realised and there is evidence that the research often fails to stand up to scientific scrutiny and its 'predictive value' is either weak or absent.DiscussionProblems with the use of animals as models of humans arise from a variety of biases and systemic failures including: 1) bias and poor practice in research methodology and data analysis; 2) lack of transparency in scientific assessment and regulation of the research; 3) long-term denial of weaknesses in cross-species translation; 4) profit-driven motives overriding patient interests; 5) lack of accountability of expenditure on animal research; 6) reductionist-materialism in science which tends to dictate scientific inquiry and control the direction of funding in biomedical research.SummaryBias in animal research needs to be addressed before medical research and healthcare decision-making can be more evidence-based. Research funding may be misdirected on studying 'disease mechanisms' in animals that cannot be replicated outside tightly controlled laboratory conditions, and without sufficient critical evaluation animal research may divert attention away from avenues of research that hold promise for human health. The potential for harm to patients and trial volunteers from reliance on biased animal data1 requires measures to improve its conduct, regulation and analysis. This article draws attention to a few of the many forms of bias in animal research that have come to light in the last decade and offers a strategy incorporating ten recommendations stated at the end of each section on bias. The proposals need development through open debate and subsequent rigorous implementation so that reviewers may determine the value of animal research to human health. The 10Rs + are protected by a Creative Commons Attribution 3.0 Unported License and therefore may be 'shared, remixed or built on, even commercially, so long as attributed by giving appropriate credit with a link to the license, and indicate if changes were made.’Electronic supplementary materialThe online version of this article (doi:10.1186/s12910-015-0043-7) contains supplementary material, which is available to authorized users.

Consideraciones Éticas Sobre El Uso De Animales No Humanos en Investigación

“…Ni toda la investigación, en su totalidad, ni todos los seres humanos, en su totalidad. 5 De acuerdo con Engel Jr., los beneficios de la investigación en animales no son tan evidentes, pues rara vez esta se traslada al cuidado de pacientes y, más aún, puede tomar años o décadas antes de que un nuevo conocimiento científico sea clínicamente aplicable, si alguna vez llega a serlo (Engel Jr., 2012). Existen otras propuestas éticas que incluyen a los animales (Regan, 1983;Taylor, 1986).…”

Building Robustness into Translational Research

“…Bias leading to poor reproducibility can occur at many levels, including selection of model and samples, execution of study, detection of findings, unequal attrition across experimental groups, and reporting (Green 2015;Hooijmans et al 2014). Most of these are generic issues of poor reproducibility and are covered elsewhere in this book.…”

Critical evaluation of challenges and future use of animals in experimentation for biomedical research

“…18 It takes almost 15 years to take approval of a drug to come to market and the cost of development is nearly $1.3 billion. 17 As Altman stated in his report in 1994, "We need less research, better research, and research done for the right reasons." 20 Like other science fields, we also need to revise the failed protocols, troubleshoot the problems in hypotheses, and take out a predictive value by systematic review and meta-analysis as tools for creating a working model with reducing economic expenditure and animal lives.…”

“…20 Like other science fields, we also need to revise the failed protocols, troubleshoot the problems in hypotheses, and take out a predictive value by systematic review and meta-analysis as tools for creating a working model with reducing economic expenditure and animal lives. 17 Humane endpoint A refinement procedure, as defined by Morton et al 21 is "Those methods which avoid, alleviate or minimize the potential pain, distress or other adverse effects suffered by the animals involved, or which enhance animal well-being." This definition endeavors the practice of humane endpoints and justify their use in experimental design effectively.…”

“…Also, on average, only 8% of animal models are able to translate further to fruitful intervention in cancer research. 17 With such failure rates, a study also published that 47 out of 53 cancer studies cannot be replicated afterwards even though they are published in esteemed journals marked as "Significant Breakthoughs." 18 Even under such grave situations, new animal studies are receiving funding to develop more animal models further on despite criticizing, reviewing, and troubleshooting the existing models available.…”