The current status of biomarkers for predicting toxicity

Expert Opinion on Drug Metabolism and Toxicology

Volumn 9, Issue 11, 2013, Pages 1391-1408

  Campion, Sarah ^a   Aubrecht, Jiri ^a   Boekelheide, Kim ^b   Brewster, David W ^c   Vaidya, Vishal S ^d   Anderson, Linnea ^b   Burt, Deborah ^a   Dere, Edward ^e   Hwang, Kathleen ^e   Pacheco, Sara ^b   Saikumar, Janani ^d   Schomaker, Shelli ^a   Sigman, Mark ^e   Goodsaid, Federico ^c  

^a PFIZER INC   (United States)

^b BROWN UNIVERSITY   (United States)

^c VERTEX PHARMACEUTICALS   (United States)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e RHODE ISLAND HOSPITAL   (United States)

Author keywords

Kidney injury; Liver; Predictive; Qualification; Testis toxicity

Indexed keywords

ALANINE AMINOTRANSFERASE; AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; ARGINASE; ARYLDIALKYLPHOSPHATASE 1; ASPARTATE AMINOTRANSFERASE; BETA 2 MICROGLOBULIN; BIOLOGICAL MARKER; CLUSTERIN; CREATINE KINASE; CYSTATIN; FIBRINOGEN; GLUTAMATE DEHYDROGENASE; GLUTATHIONE TRANSFERASE; GLUTATHIONE TRANSFERASE ALPHA; IDITOL DEHYDROGENASE; KIDNEY INJURY MOLECULE 1; MALATE DEHYDROGENASE; MESSENGER RNA; MICRORNA; MUCIN 1; MYOGLOBIN; N ACETYL BETA GLUCOSAMINIDASE; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; PARVALBUMIN; POLYMYXIN DERIVATIVE; PURINE NUCLEOSIDE PHOSPHORYLASE; SIRTUIN 3; TROPONIN I; TROPONIN T; UNINDEXED DRUG;

BLOOD VESSEL INJURY; CARDIOTOXICITY; DNA METHYLATION; DRUG SAFETY; HUMAN; KIDNEY INJURY; LIVER INJURY; LIVER TOXICITY; MUSCLE INJURY; MUSCLE TOXICITY; NONHUMAN; PREDICTIVE VALUE; QUANTITATIVE ANALYSIS; REVIEW; RISK ASSESSMENT; SENSITIVITY AND SPECIFICITY; TESTIS DISEASE; TESTIS INJURY; TOXICITY TESTING;

ACUTE KIDNEY INJURY; ANIMALS; BIOLOGICAL MARKERS; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HUMANS; KIDNEY; MALE; TESTICULAR DISEASES; TESTIS;

EID: 84886027673     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2013.827170     Document Type: Review

References (122)

1. Olson H, Betton G, Robinson D, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 2000;32(1):56-67
2. Sistare FD, DeGeorge JJ. Preclinical predictors of clinical safety: opportunities for improvement. Clin Pharmacol Ther 2007;82(2):210-14 (Pubitemid 47075341)
3. Shanks N, Greek R, Greek J. Are animal models predictive for humans Philos Ethics Humanit Med 2009;4:2
4. Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates Nat Rev Drug Discov 2004;3(8):711-15 (Pubitemid 39173511)
5. Atkinson AJ, Colburn WA, DeGruttola VG, et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89-95 (Pubitemid 32225406)
6. NCI dictionary of terms. Available from: http://www.cancer.gov/dictionary cdrid=45618
7. Taube SE. Biomarkers in oncology. Ann NY Acad Sci 2009;1180:111-18
8. Amur S, Frueh FW, Lesko LJ, Huang SM. Integration and use of biomarkers in drug development, regulation and clinical practice: a US regulatory perspective. Biomarkers Med 2008;2(3):305-11
9. Jones R. Biomarkers: casting the net wide. Nature 2010;466(7310):S11-12
10. Dienstmann R, Rodon J, Tabernero J. Biomarker-driven patient selection for early clinical trials. Curr Opin Oncol 2013;25(3):305-12
11. George S, Reichardt P, Lechner T, et al. Hypertension as a potential biomarker of efficacy in patients with gastrointestinal stromal tumor treated with sunitinib. Ann Oncol 2012;23(12):3180-7
12. Muller PY, Dieterle F. Tissue-specific, non-invasive toxicity biomarkers: translation from preclinical safety assessment to clinical safety monitoring. Expert Opin Drug Metab Toxicol 2009;5(9):1023-38
13. O'Brien PJ. Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology 2008;245(3):206-18
14. Piccini JP, Whellan DJ, Berridge BR, et al. Current challenges in the evaluation of cardiac safety during drug development: translational medicine meets the Critical Path Initiative. Am Heart J 2009;158(3):317-26
15. Tarrant JM. Blood cytokines as biomarkers of in vivo toxicity in preclinical safety assessment: considerations for their use. Toxicol Sci 2010;117(1):4-16
16. Mikaelian I, Scicchitano M, Mendes O, et al. Frontiers in preclinical safety biomarkers: microRNAs and messenger RNAs. Toxicol Pathol 2013;41(1):18-31
17. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116(2):281-97
18. Mendrick DL. Genomic and genetic biomarkers of toxicity. Toxicology 2008;245(3):175-81
19. Fielden MR, Brennan R, Gollub J. A gene expression biomarker provides early prediction and mechanistic assessment of hepatic tumor induction by nongenotoxic chemicals. Toxicol Sci 2007;99(1):90-100 (Pubitemid 47250370)
20. Goodsaid FM. Identification and measurement of genomic biomarkers of nephrotoxicity. J Pharmacol Toxicol Methods 2004;49(3):183-6 (Pubitemid 38686656)
21. Davis JW II, Goodsaid FM, Bral CM, et al. Quantitative gene expression analysis in a nonhuman primate model of antibiotic-induced nephrotoxicity. Toxicol Appl Pharmacol 2004;200(1):16-26 (Pubitemid 39286670)
22. Collings FB, Vaidya VS. Novel technologies for the discovery and quantitation of biomarkers of toxicity. Toxicology 2008;245(3):167-74
23. Amacher DE. The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity. Toxicol Appl Pharmacol 2010;245(1):134-42
24. Goodsaid F. Are we ready for novel preclinical safety biomarkers Preclinica 2004;2(4):1-3
25. Jurewicz J, Hanke W, Radwan M, Bonde JP. Environmental factors and semen quality. Int J Occup Med Environ Health 2009;22(4):305-29
26. Boekelheide K. Commentary on "incidence and nature of testicular toxicity findings .". Birth Defects Res B Dev Reprod Toxicol 2011;92(6):501-3
27. Whorton D, Krauss RM, Marshall S, Milby TH. Infertility in male pesticide workers. Lancet 1977;2(8051):1259-61 (Pubitemid 8243372)
28. Whorton D, Milby TH, Krauss RM, Stubbs HA. Testicular function in DBCP exposed pesticide workers. J Occup Med 1979;21(3):161-6 (Pubitemid 9137366)
29. Eaton M, Schenker M, Whorton MD, et al. Seven-year follow-up of workers exposed to 1,2-dibromo-3-chloropropane. J Occup Med 1986;28(11):1145-50 (Pubitemid 17193190)
30. Bonde JP, Giwercman A, Ernst E. Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options. Occup Environ Med 1996;53(8):511-19 (Pubitemid 26291788)
31. Klinefelter GR. Saga of a sperm fertility biomarker. Anim Reprod Sci 2008;105(1-2):90-103
32. Ostermeier GC, Dix DJ, Miller D, et al. Spermatozoal RNA profiles of normal fertile men. Lancet 2002;360(9335):772-7 (Pubitemid 35247708)
33. Wang H, Zhou Z, Xu M, et al. A spermatogenesis-related gene expression profile in human spermatozoa and its potential clinical applications. J Mol Med (Berl) 2004;82(5):317-24 (Pubitemid 38680289)
34. Aoki VW, Liu L, Carrell DT. A novel mechanism of protamine expression deregulation highlighted by abnormal protamine transcript retention in infertile human males with sperm protamine deficiency. Mol Hum Reprod 2006;12(1):41-50
35. Steger K, Wilhelm J, Konrad L, et al. Both protamine-1 to protamine-2 mRNA ratio and Bcl2 mRNA content in testicular spermatids and ejaculated spermatozoa discriminate between fertile and infertile men. Hum Reprod 2008;23(1):11-16 (Pubitemid 351767333)
36. Miller D, Ostermeier GC. Towards a better understanding of RNA carriage by ejaculate spermatozoa. Hum Reprod Update 2006;12(6):757-67 (Pubitemid 44605513)
37. Trasler JM. Gamete imprinting: setting epigenetic patterns for the next generation. Reprod Fertil Dev 2006;18(1-2):63-9 (Pubitemid 41831076)
38. Hammoud SS, Purwar J, Pflueger C, et al. Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril 2010;94(5):1728-33
39. Houshdaran S, Cortessis VK, Siegmund K, et al. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One 2007;2(12):e1289
40. Marques CJ, Carvalho F, Sousa M, Barros A. Genomic imprinting in disruptive spermatogenesis. Lancet 2004;363(9422):1700-2 (Pubitemid 38670329)
41. Marques CJ, Costa P, Vaz B, et al. Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol Hum Reprod 2008;14(2):67-74
42. Poplinski A, Tuttelmann F, Kanber D, et al. Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2/H19 ICR1. Int J Androl 2010;33(4):642-9
43. Kobayashi H, Sato A, Otsu E, et al. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet 2007;16(21):2542-51 (Pubitemid 47617721)
44. Pathak S, Kedia-Mokashi N, Saxena M, et al. Effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 locus-specific DNA methylation in rat spermatozoa and its association with embryo loss. Fertil Steril 2009;91(5 Suppl):2253-63
45. Sato A, Hiura H, Okae H, et al. Assessing loss of imprint methylation in sperm from subfertile men using novel methylation polymerase chain reaction Luminex analysis. Fertil Steril 2011;95(1):129-34; 34 e1-4
46. Boissonnas CC, Abdalaoui HE, Haelewyn V, et al. Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile men. Eur J Hum Genet 2010;18(1):73-80
47. Wu W, Shen O, Qin Y, et al. Idiopathic male infertility is strongly associated with aberrant promoter methylation of methylenetetrahydrofolate reductase (MTHFR). PLoS ONE 2010;5(11):e13884
48. Navarro-Costa P, Nogueira P, Carvalho M, et al. Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm. Hum Reprod 2010;25(10):2647-54
49. Aston KI, Punj V, Liu L, Carrell DT. Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis. Fertil Steril 2012;97(2):285-92
50. Chan D, Delbes G, Landry M, et al. Epigenetic alterations in sperm DNA associated with testicular cancer treatment. Toxicol Sci 2012;125(2):532-43
51. Pacheco SE, Anderson LM, Sandrof MA, et al. Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury in the Fischer 344 rat. PLoS One 2012;7(8):e44280
52. Pacheco SE, Houseman EA, Christensen BC, et al. Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. PLoS One 2011;6(6):e20280
53. Carrell DT. Epigenetics of the male gamete. Fertil Steril 2012;97(2):267-74
54. Jenkins TG, Carrell DT. The paternal epigenome and embryogenesis: poising mechanisms for development. Asian J Androl 2011;13(1):76-80
55. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol 2013;24(1):37-42
56. Bucaloiu ID, Kirchner HL, Norfolk ER, et al. Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 2012;81(5):477-85
57. Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol 2008;48:463-93 (Pubitemid 351738161)
58. Hodgson S, Nieuwenhuijsen MJ, Hansell A, et al. Excess risk of kidney disease in a population living near industrial plants. Occup Environ Med 2004;61(8):717-19 (Pubitemid 38998118)
59. Van Vleet TR, Schnellmann RG. Toxic nephropathy: environmental chemicals. Semin Nephrol 2003;23(5):500-8 (Pubitemid 37176695)
60. Wu X, Liang Y, Jin T, et al. Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice. Environ Res 2008;108(2):233-8
61. Nordberg GF, Jin T, Wu X, et al. Prevalence of kidney dysfunction in humans-relationship to cadmium dose, metallothionein, immunological and metabolic factors. Biochimie 2009;91(10):1282-5
62. Gonick HC. Nephrotoxicity of cadmium & lead. Indian J Med Res 2008;128(4):335-52
63. Roels HA, Hoet P, Lison D. Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Ren Fail 1999;21(3-4):251-62 (Pubitemid 29318191)
64. Roels H, Lauwerys R, Konings J, et al. Renal function and hyperfiltration capacity in lead smelter workers with high bone lead. Occup Environ Med 1994;51(8):505-12 (Pubitemid 24248951)
65. de Burbure C, Buchet JP, Leroyer A, et al. Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels. Environ Health Perspect 2006;114(4):584-90
66. Jarup L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167-82 (Pubitemid 38248496)
67. Hassan AM, Sheashaa HA, Fattah MF, et al. Study of ochratoxin A as an environmental risk that causes renal injury in breast-fed Egyptian infants. Pediatr Nephrol 2006;21(1):102-5 (Pubitemid 43040202)
68. Petrik J, Zanic-Grubisic T, Barisic K, et al. Apoptosis and oxidative stress induced by ochratoxin A in rat kidney. Arch Toxicol 2003;77(12):685-93 (Pubitemid 38088027)
69. Pozdzik AA, Salmon IJ, Debelle FD, et al. Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation. Kidney Int 2008;73(5):595-607 (Pubitemid 351264108)
70. Isnard Bagnis C, Deray G, Baumelou A, et al. Herbs and the kidney. Am J Kidney Dis 2004;44(1):1-11 (Pubitemid 38880921)
71. Grollman AP, Jelakovic B. Role of environmental toxins in endemic (Balkan) nephropathy. October 2006, Zagreb, Croatia. J Am Soc Nephrol 2007;18(11):2817-23 (Pubitemid 350064082)
72. Grollman AP, Shibutani S, Moriya M, et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci USA 2007;104(29):12129-34 (Pubitemid 47185641)
73. Soderland P, Lovekar S, Weiner DE, et al. Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis 2010;17(3):254-64
74. Bacchetta J, Dubourg L, Juillard L, Cochat P. Non-drug-induced nephrotoxicity. Pediatr Nephrol (Berlin, Germany) 2009;24(12):2291-300
75. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med 1996;334(22):1448-60 (Pubitemid 126590563)
76. Anders MW. Metabolism of drugs by the kidney. Kidney Int 1980;18(5):636-47 (Pubitemid 11204064)
77. Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 2011;121(11):4210-21
78. Ichimura T, Bonventre JV, Bailly V, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998;273(7):4135-42 (Pubitemid 28103282)
79. Ichimura T, Asseldonk EJ, Humphreys BD, et al. Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest 2008;118(5):1657-68 (Pubitemid 351632370)
80. Vaidya VS, Ramirez V, Ichimura T, et al. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 2006;290(2):F517-29 (Pubitemid 43725006)
81. Vaidya VS, Ozer JS, Dieterle F, et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 2010;28(5):478-85
82. Vaidya VS, Waikar SS, Ferguson MA, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci 2008;1(3):200-8 (Pubitemid 352831522)
83. Vaidya VS, Ford GM, Waikar SS, et al. A rapid urine test for early detection of kidney injury. Kidney Int 2009;76(1):108-14
84. Bonventre JV, Yang L. Kidney injury molecule-1. Curr Opin Crit Care 2010;16(6):556-61
85. Peralta CA, Katz R, Bonventre JV, et al. Associations of urinary levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) with kidney function decline in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis 2012;60(6):904-11
86. Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 2012;34(1):43-62
87. Krishnamoorthy A, Ajay AK, Hoffmann D, et al. Fibrinogen {beta}-derived B{beta}15-42 peptide protects against kidney ischemia/reperfusion injury. Blood 2011;118(7):1934-42
88. Ajay AK, Saikumar J, Bijol V, Vaidya VS. Heterozygosity for fibrinogen results in efficient resolution of kidney ischemia reperfusion injury. PLoS One 2012;7(9):e45628
89. Hoffmann D, Bijol V, Krishnamoorthy A, et al. Fibrinogen excretion in the urine and immunoreactivity in the kidney serves as a translational biomarker for acute kidney injury. Am J Pathol 2012;181(3):818-28
90. Adams RA, Bauer J, Flick MJ, et al. The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J Exp Med 2007;204(3):571-82 (Pubitemid 46457080)
91. Petzelbauer P, Zacharowski PA, Miyazaki Y, et al. The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury. Nat Med 2005;11(3):298-304 (Pubitemid 40460558)
92. Sorensen I, Rong S, Susnik N, et al. Bbeta(15-42) attenuates the effect of ischemia-reperfusion injury in renal transplantation. J Am Soc Nephrol 2011;22(10):1887-96
93. Cruz-Topete D, Iwaki T, Ploplis VA, Castellino FJ. Delayed inflammatory responses to endotoxin in fibrinogen-deficient mice. J Pathol 2006;210(3):325-33 (Pubitemid 44660511)
94. Drew AF, Tucker HL, Liu H, et al. Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice. Am J Physiol Renal Physiol 2001;281(6):F1157-63
95. Akassoglou K, Adams RA, Bauer J, et al. Fibrin depletion decreases inflammation and delays the onset of demyelination in a tumor necrosis factor transgenic mouse model for multiple sclerosis. Proc Natl Acad Sci USA 2004;101(17):6698-703 (Pubitemid 38586037)
96. Suh TT, Holmback K, Jensen NJ, et al. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev 1995;9(16):2020-33
97. Saikumar J, Hoffmann D, Kim TM, et al. Expression, circulation, and excretion profile of microRNA-21,-155, and-18a following acute kidney injury. Toxicol Sci 2012;129(2):256-67
98. Lawrie CH, Gal S, Dunlop HM, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 2008;141(5):672-5 (Pubitemid 351667616)
99. Asaga S, Kuo C, Nguyen T, et al. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem 2011;57(1):84-91
100. Cheng Y, Tan N, Yang J, et al. A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond) 2010;119(2):87-95
101. Wang K, Zhang S, Marzolf B, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009;106(11):4402-7
102. Burt D, Crowell SJ, Ackley DC, et al. Application of emerging biomarkers of acute kidney injury in development of kidney-sparing polypeptide-based antibiotics. Drug Chem Toxicol; In press. . Excellent example of a preclinical biomarker-based strategy for identifying drug candidates with improved safety profiles.
103. Schomaker S, Warner R, Bock J, et al. Assessment of emerging biomarkers of liver injury in human subjects. Toxicol Sci 2013;132(2):276-83
104. Goodsaid FM, Frueh FW, Mattes W. The predictive safety testing consortium: a synthesis of the goals, challenges and accomplishments of the critical path. Drug Discov Today Technol 2007;4(2):47-50 (Pubitemid 350244443)
105. Goodsaid FM, Blank M, Dieterle F, et al. Novel biomarkers of acute kidney toxicity. Clin Pharmacol Ther 2009;86(5):490-6
106. Bonventre JV, Vaidya VS, Schmouder R, et al. Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol 2010;28(5):436-40
107. Lock EA. Sensitive and early markers of renal injury: where are we and what is the way forward Toxicol Sci 2010;116(1):1-4
108. Sistare FD, Dieterle F, Troth S, et al. Towards consensus practices to qualify safety biomarkers for use in early drug development. Nat Biotechnol 2010;28(5):446-54
109. Vaidya VS, Bonventre JV. Biomarkers: in medicine, drug discovery, and environmental health. John Wiley & SOns, Inc; Hoboken, NJ: 2010
110. Ozer J, Ratner M, Shaw M, et al. The current state of serum biomarkers of hepatotoxicity. Toxicology 2008;245(3):194-205
111. FDA. Guidance for Industry. Drug-Induced Liver Injury: premarketing Clinical Evaluation. 2007. Available from: http://www.fda.gov/downloads/Drugs/ GuidanceCompliance RegulatoryInformation/Guidances/UCM174090.pdf
112. Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011;89(6):806-15
113. Dieterle F. The European IMI SAFE-T consortium: qualification of translation safety biomarkers. Toxicol Lett 2009;189:S157
114. FDA. Guidance for Industry. Pharmacogenomic Data Submissions. 2005. Available from: www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126957. pdf
115. FDA. Critical Path Opportunities List. 2006. Available from: www.fda.gov/downloads/scienceresearch/specialtopics/CriticalPathinitiative/ CriticalPathOpportunitiesreports/UCM077258.pdf
116. Altar CA, Amakye D, Bounos D, et al. A prototypical process for creating evidentiary standards for biomarkers and diagnostics. Clin Pharmacol Ther 2008;83(2):368-71
117. Institute of Medicine of the National Academy of Sciences. Consensus Report. Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease; 2010
118. Goodsaid FM, Freuh F. Regulatory guidance and validation of toxicologic biomarkers. In: DeCaprio AP, editor. Toxicologic biomarkers. Taylor & Francis Group; New York: 2006. p. 187-220
119. Goodsaid F, Frueh F. Process map proposal for the validation of genomic biomarkers. Pharmacogenomics 2006;7(5):773-82 (Pubitemid 44225912)
120. Goodsaid FM, Frueh FW, Mattes W. Strategic paths for biomarker qualification. Toxicology 2008;245(3):219-23
121. FDA. Guidance for Industry. Qualification Process for Drug Development Tools. 2010. Available from: http://www.fda. gov/downloads/Drugs/ GuidanceCompliance RegulatoryInformation/Guidances/UCM230597.pdf
122. FDA. Biomarker Qualification Program. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ DrugDevelopmentToolsQualification Program/ucm284076.htm