An analysis of the use of animal models in predicting human toxicology and drug safety

ATLA Alternatives to Laboratory Animals

Volumn 42, Issue 3, 2014, Pages 181-199

  Bailey, Jarrod ^a   Thew, Michelle ^a   Balls, Michael ^b  

^a British Union for the Abolition of Vivisection (BUAV)   (United Kingdom)

^b RUSSELL AND BURCH HOUSE   (United Kingdom)

Author keywords

Animals; Dog; Drug development; Mouse; Preclinical testing; Rabbit; Rat; Toxicology

Indexed keywords

ANIMAL MODEL; ARTICLE; CANINE MODEL; CONTROLLED STUDY; DRUG CLASSIFICATION; DRUG EFFECT; DRUG INDUSTRY; DRUG SAFETY; DRUG SCREENING; DRUG TISSUE LEVEL; HEALTH HAZARD; HUMAN; HUMAN VERSUS ANIMAL COMPARISON; LIKELIHOOD RATIO; MEDICAL DICTIONARY FOR REGULATORY ACTIVITIES; MOUSE MODEL; NONHUMAN; PRIORITY JOURNAL; RABBIT MODEL; RAT MODEL; SAMPLE SIZE; SENSITIVITY AND SPECIFICITY; TOXICITY TESTING; ADVERSE DRUG REACTION; ANIMAL; ANIMAL EXPERIMENT; MOUSE; RABBIT; RAT; STATISTICS; TOXICOLOGY;

ANIMALIA; CANIS FAMILIARIS; ORYCTOLAGUS CUNICULUS; RATTUS;

ANIMAL EXPERIMENTATION; ANIMALS; DRUG EVALUATION, PRECLINICAL; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HUMANS; MICE; MODELS, ANIMAL; RABBITS; RATS; TOXICOLOGY;

EID: 84907424934     PISSN: 02611929     EISSN: 26323559     Source Type: Journal    
DOI: 10.1177/026119291404200306     Document Type: Article

References (73)

1. Anon. (2004). Directive 2004/27/EEC of the European Parliament and the Council of 31 March 2004, amending Directive 2001/83/EC on the Community code relating to medicinal products for human use. Official Journal of the European Union L136, 30.04.2004, 34-57.
2. Anon. (1938). Federal Food, Drug and Cosmetics Act. Silver Spring, MD, USA: US Food and Drug Administration. Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/default.htm (Accessed 28.05.14).
3. Aithal, G.P. (2010). Mind the gap. ATLA 38, Suppl. 1, 1-4.
4. Duyk, G. (2003). Attrition and translation. Science, New York 302, 603-605.
5. Kola, I. & Landis, J. (2004). Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery 3, 711-715.
6. Wehling, M. (2011). Drug development in the light of translational science: Shine or shade? Drug Discovery Today 16, 1076-1083.
7. DiMasi, J.A. (2014). Pharmaceutical R&D performance by firm size: Approval success rates and economic returns. American Journal of Therapeutics 21, 26-34.
8. UK Home Office (2013). Statistics of Scientific Procedures on Living Animals - Great Britain 2012. HC 549, 60pp. London, UK: The Stationery Office.
9. Greaves, P., Williams, A. & Eve, M. (2004). First dose of potential new medicines to humans: How animals help. Nature Reviews Drug Discovery 3, 226-236.
10. Heywood, R. (1981). Target organ toxicity. Toxicology Letters 8, 349-358.
11. Schein, P.S., Davis, R.D., Carter, S., Newman, J., Schein, D.R. & Rall, D.P. (1970). The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man. Clinical Pharmacology & Therapeutics 11, 3-40.
12. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., Dorato, M., Van Deun, K., Smith, P., Berger, B. & Heller, A. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology & Pharmacology 32, 56-67.
13. Altman, D.G. & Bland, J.M. (1994). Diagnostic tests 2: Predictive values. BMJ 309, 102.
14. Bailey, J., Thew, M. & Balls, M. (2013). An analysis of the use of dogs in predicting human toxicology and drug safety. ATLA 41, 335-350.
15. Anon. (2012). Likelihood Ratios. Oxford, UK: Centre for Evidence Based Medicine (CEBM). Available at: http://www.cebm.net/index.aspx?o=1043 (Accessed 28.05.13).
16. Greek, R. & Menache, A. (2013). Systematic reviews of animal models: Methodology versus epistemology. International Journal of Medical Sciences 10, 206-221.
17. Grimes, D.A. & Schulz, K.F. (2005). Refining clinical diagnosis with likelihood ratios. Lancet 365, 1500-1505.
18. Hasiwa, N., Bailey, J., Clausing, P., Daneshian, M., Eileraas, M., Farkas, S., Gyertyan, I., Hubrecht, R., Kobel, W., Krummenacher, G., Leist, M., Lohi, H., Miklosi, A., Ohl, F., Olejniczak, K., Schmitt, G., Sinnett-Smith, P., Smith, D., Wagner, K., Yager, J.D., Zurlo, J. & Hartung, T. (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. ALTEX 28, 326-340.
19. CAAT-Europe (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. Centre for Alternatives to Animal Testing-Europe Workshop, 21-23 June 2011. Konstanz, Germany: Centre for Alternatives to Animal Testing-Europe.
20. CAAT (2011). Critical evaluation of the use of dogs in biomedical research and testing. Centre for Alternatives to Animal Testing Workshop, 21-23 January 2011. Baltimore, MA, USA: Johns Hopkins Bloomberg School of Public Health.
21. van Meer, P.J., Kooijman, M., Gispen-de Wied, C.C., Moors, E.H. & Schellekens, H. (2012). The ability of animal studies to detect serious post marketing adverse events is limited. Regulatory Toxicology & Pharmacology 64, 345-349.
22. Igarashi, T., Nakane, S. & Kitagawa, T. (1995). Predictability of clinical adverse reactions of drugs by general pharmacology studies. Journal of Toxicological Sciences 20, 77-92.
23. Broadhead, C.L., Jennings, M. & Combes, R. (1999). A Critical Evaluation of the Use of Dogs in the Regulatory Toxicity Testing of Pharmaceuticals, 106pp. Nottingham, UK: Fund for the Replacement of Animals in Medical Experiments (FRAME).
24. Litchfield, J.T.J. (1962). Symposium on clinical drug evaluation and human pharmacology. XVI. Evaluation of the safety of new drugs by means of tests in animals. Clinical Pharmacology & Therapeutics 3, 665-672.
25. Bailey, J. (2008). Developmental toxicity testing: Protecting future generations? ATLA 36, 718-721.
26. Schardein, J. (2000). Chemically Induced Birth Defects, 3rd edn, 1019pp. Boca Raton, FL, USA: CRC Press.
27. Spanhaak, S., Cook, D., Barnes, J. & Reynolds, J. (2008). Species Concordance for Liver Injury, 6pp. Cambridge, UK: Biowisdom Ltd. Available at: http://www.biowisdom.com/files/SIP-Board-Species-Concordance.pdf (Accessed 28.05.14).
28. Matthews, R.A. (2008). Medical progress depends on animal modelsdoesn't it? Journal of the Royal Society of Medicine 101, 95-98.
29. Barnes, J.C., Matis, S., Kenna, G., Swinton, J., Bradley, P.M., Day, N.C., Reed, J.Z., Reynolds, J. & Cook, D. (2008). The Safety Intelligence Program: An Intelligence Network for Drug-induced Liver Injury, 2pp. Cambridge, UK: Biowisdom Ltd. Available at: http://bioblog.instem.com/downloads/Carboxylic-acids-A4.pdf (Accessed 28.05.14).
30. Sidaway, J.R.M., Roberts, S., Huby, R., Nicholson, A., Pemberton, J., South, M., Noeske, T., Engkvist, O., Bradley, P. & Reed, J. (2012). Drug Toxicities Associated With Pharmacological Activity: Using Harmonised Data to Make the 'Known' Visible, 2pp. Macclesfield, UK: Safety Assessment, AstraZeneca.
31. Fourches, D., Barnes, J.C., Day, N.C., Bradley, P., Reed, J.Z. & Tropsha, A. (2010). Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species. Chemical Research in Toxicology 23, 171-183.
32. Greco, I., Day, N., Riddoch-Contreras, J., Reed, J., Soininen, H., Kloszewska, I., Tsolaki, M., Vellas, B., Spenger, C., Mecocci, P., Wahlund, L.O., Simmons, A., Barnes, J. & Lovestone, S. (2012). Alzheimer's disease biomarker discovery using in silico literature mining and clinical validation. Journal of Translational Medicine 10, 217.
33. Wandall, B., Hansson, S.O. & Rudén, C. (2007). Bias in toxicology. Archives of Toxicology 81, 605-617.
34. Hackam, D.G. (2007). Translating animal research into clinical benefit. BMJ 334, 163-164.
35. ter Riet, G., Korevaar, D.A., Leenaars, M., Sterk, P.J., Van Noorden, C.J., Bouter, L.M., Lutter, R., Elferink, R.P. & Hooft, L. (2012). Publication bias in laboratory animal research: A survey on magnitude, drivers, consequences and potential solutions. PLoS One 7, e43404.
36. Briel, M., Muller, K.F., Meerpohl, J.J., von Elm, E., Lang, B., Motschall, E., Gloy, V., Lamontagne, F., Schwarzer, G. & Bassler, D. (2013). Publication bias in animal research: A systematic review protocol. Systematic Reviews 2, 23.
37. van der Worp, H.B., Howells, D.W., Sena, E.S., Porritt, M.J., Rewell, S., O'Collins, V. & Macleod, M.R. (2010). Can animal models of disease reliably inform human studies? PLoS Medicine 7, e1000245.
38. Sena, E.S., van der Worp, H.B., Bath, P.M., Howells, D.W. & Macleod, M.R. (2010). Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. PLoS Biology 8, e1000344.
39. Perel, P., Roberts, I., Sena, E., Wheble, P., Briscoe, C., Sandercock, P., Macleod, M., Mignini, L.E., Jayaram, P. & Khan, K.S. (2007). Comparison of treatment effects between animal experiments and clinical trials: Systematic review. BMJ 334, 197.
40. Schott, G., Pachl, H., Limbach, U., Gundert-Remy, U., Ludwig, W.D. & Lieb, K. (2010). The financing of drug trials by pharmaceutical companies and its consequences. Part 1: A qualitative, systematic review of the literature on possible influences on the findings, protocols, and quality of drug trials. Deutsches Arzteblatt International 107, 279-285.
41. Kilkenny, C., Parsons, N., Kadyszewski, E., Festing, M.F., Cuthill, I.C., Fry, D., Hutton, J. & Altman, D.G. (2009). Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One 4, e7824.
42. Anon. (2010). Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union L276, 20.10.2010, 33-79.
43. US FDA (2004). Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, 31pp. Silver Spring, MD, USA: US Department of Health and Human Services, Food and Drug Administration.
44. Issa, A.M., Phillips, K.A., Van Bebber, S., Nidamarthy, H.G., Lasser, K.E., Haas, J.S., Alldredge, B.K., Wachter, R.M. & Bates, D.W. (2007). Drug withdrawals in the United States: A systematic review of the evidence and analysis of trends. Current Drug Safety 2, 177-185.
45. Bennani, Y.L. (2011). Drug discovery in the next decade: Innovation needed ASAP. Drug Discovery Today 16, 779-792.
46. Eichler, H.G., Aronsson, B., Abadie, E. & Salmonson, T. (2010). New drug approval success rate in Europe in 2009. Nature Reviews Drug Discovery 9, 355-356.
47. Hughes, B. (2008). 2007 FDA drug approvals: A year of flux. Nature Reviews Drug Discovery 7, 107-109.
48. Hartung, T. (2009). Toxicology for the twenty-first century. Nature, London 460, 208-212.
49. Harding, A. (2004). More compounds failing phase I. [The Scientist, 06.08.04]. Available at: www.the-scientist.com/?articles.view/articleNo/23003/title/More-compounds-failing-Phase-I/ (Accessed 28.05.14).
50. Okie, S. (2006). Access before approval - a right to take experimental drugs? New England Journal of Medicine 355, 437-440.
51. Aurup, P. (2012). Er Danmark et Attraktivt Land for Klinisk Forskning? (Is Denmark an Attractive Country for Clinical Research?), 23pp. Ballerup, Denmark: MSD Laboratories. Available at: http://di.dk/SiteCollectionDocuments/Opinion/Sundhed/Høring/Præsentation%20-%20Peter%20Aurup,%20Merck.pdf (Accessed 28.05.14).
52. Anon. (1990). FDA Drug Review: Post Approval Risks 1976-1985. GAO/PEMD-90-15, 132pp. Washington, DC, USA: US General Accounting Office.
53. Lazarou, J., Pomeranz, B.H. & Corey, P.N. (1998). Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA 279, 1200-1205.
54. Nishimuta, H., Nakagawa, T., Nomura, N. & Yabuki, M. (2013). Species differences in hepatic and intestinal metabolic activities for 43 human cytochrome P450 substrates between humans and rats or dogs. Xenobiotica 43, 948-955.
55. Martinez, M.N., Antonovic, L., Court, M., Dacasto, M., Fink-Gremmels, J., Kukanich, B., Locuson, C., Mealey, K., Myers, M.J. & Trepanier, L. (2013). Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics. Drug Metabolism Reviews 45, 218-230.
56. Zhou, S.F., Liu, J.P. & Chowbay, B. (2009). Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metabolism Reviews 41, 89-295.
57. Guengerich, F.P. (1997). Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chemico-Biological Interactions 106, 161-182.
58. Nishimuta, H., Sato, K., Mizuki, Y., Yabuki, M. & Komuro, S. (2011). Species differences in intestinal metabolic activities of cytochrome P450 isoforms between cynomolgus monkeys and humans. Drug Metabolism & Pharmacokinetics 26, 300-306.
59. Komura, H. & Iwaki, M. (2011). In vitro and in vivo small intestinal metabolism of CYP3A and UGT substrates in preclinical animals species and humans: Species differences. Drug Metabolism Reviews 43, 476-498.
60. Shimada, T., Mimura, M., Inoue, K., Nakamura, S., Oda, H., Ohmori, S. & Yamazaki, H. (1997). Cytochrome P450-dependent drug oxidation activities in liver microsomes of various animal species including rats, guinea pigs, dogs, monkeys, and humans. Archives of Toxicology 71, 401-408.
61. Turpeinen, M., Ghiciuc, C., Opritoui, M., Tursas, L., Pelkonen, O. & Pasanen, M. (2007). Predictive value of animal models for human cytochrome P450 (CYP)-mediated metabolism: A comparative study in vitro. Xenobiotica 37, 1367-1377.
62. Antonovic, L. & Martinez, M. (2011). Role of the cytochrome P450 enzyme system in veterinary pharmacokinetics: Where are we now? Where are we going? Future Medicinal Chemistry 3, 855-879.
63. Gad, S.C. (2006). Animal Models in Toxicology, 952pp. Boca Raton, FL, USA: CRC Press.
64. Lewis, D.F., Ioannides, C. & Parke, D.V. (1998). Cytochromes P450 and species differences in xenobiotic metabolism and activation of carcinogen. Environmental Health Perspectives 106, 633-641.
65. Gonzalez, F.J. (2004). Cytochrome P450 humanised mice. Human Genomics 1, 300-306.
66. Nelson, D.R., Zeldin, D.C., Hoffman, S.M., Maltais, L.J., Wain, H.M. & Nebert, D.W. (2004). Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 14, 1-18.
67. Honkakoski, P. & Negishi, M. (1997). The structure, function, and regulation of cytochrome P450 2A enzymes. Drug Metabolism Reviews 29, 977-996.
68. Hewitt, N.J., Lecluyse, E.L. & Ferguson, S.S. (2007). Induction of hepatic cytochrome P450 enzymes: Methods, mechanisms, recommendations, and in vitro-in vivo correlations. Xenobiotica 37, 1196-1224.
69. Graham, M.J. & Lake, B.G. (2008). Induction of drug metabolism: Species differences and toxicological relevance. Toxicology 254, 184-191.
70. Zhang, W., Roederer, M.W., Chen, W.Q., Fan, L. & Zhou, H.H. (2012). Pharmacogenetics of drugs withdrawn from the market. Pharmacogenomics 13, 223-231.
71. Spielmann, H., Kral, V., Schafer-Korting, M., Seidle, T., McIvor, E., Rowan, A. & Schoeters, G. (2011). The AXLR8 Consortium. Alternative Testing Strategies, Progress Report 2011, 364pp. Berlin, Germany: Institute of Pharmacy, Free University of Berlin. Available at: http://scrtox.eu/~scrtox/images/stories/AXLR8-2011.pdf (Accessed 28.05.14).
72. Committee on Toxicity Testing and Assessment of Environmental Agents, National Research Council (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy, 216pp. Washington, DC, USA: National Academies Press.
73. YouGov plc. (2009). Public Opinion. London, UK: European Coalition to End Animal Experiments. Available at: http://www.eceae.org/en (Accessed 28.05.14).