Bioinformatics advances for clinical biomarker development

Expert Opinion on Medical Diagnostics

Volumn 6, Issue 1, 2012, Pages 39-48

  Pritzker, Kenneth P H ^a   Pritzker, Laura B ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b Rna Diagnostics Inc   (Canada)

Author keywords

bioinformatics; bioinformatics databases; biomarker; biomarker qualification; biomarker validation; clinical utility; comparative effectiveness; predictive biomarker; prognostic biomarker; specimen repository

Indexed keywords

BIOLOGICAL MARKER;

ALGORITHM; BIOINFORMATICS; CLINICAL PRACTICE; COMPARATIVE EFFECTIVENESS; DATA BASE; DISEASE ACTIVITY; DISEASE COURSE; MATHEMATICAL MODEL; MEDICAL INFORMATION SYSTEM; PROGNOSIS; REVIEW; STANDARDIZATION; STATISTICAL ANALYSIS; SURVIVAL RATE; VALIDATION PROCESS;

EID: 84055200150     PISSN: 17530059     EISSN: 17530067     Source Type: Journal    
DOI: 10.1517/17530059.2012.634797     Document Type: Review

References (98)

1. SciClips Diagnostic and Prognostic biomarkers database. Available from:
2. Chou R, Croswell JM, Dana T, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services task force. Ann Intern Med 7 Oct 2011 [Epub ahead of print]
3. Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009;27(12):2091-6
4. Niedbala RS, Mauck C, Harrison P, Doncel GF. Biomarker discovery: validation and decision-making in product development. Sex Transm Dis 2009;36(Suppl 3):S76-80
5. Negm RS, Verma M, Srivastava S. The promise of biomarkers in cancer screening and detection. Trends Mol Med 2002;8(6):288-93 (Pubitemid 34568384)
6. Biomarkers Definitions Working Group B. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89-95
7. Wagner JA. Overview of biomarkers and surrogate endpoints in drug development. Dis Markers 2002;18(2):41-6 (Pubitemid 35191657)
8. Saad ED, Katz A, Hoff PM, Buyse M. Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature. Ann Oncol 2010;21(1):7-12
9. Buyse M, Sargent DJ, Grothey A, et al. Biomarkers and surrogate end points-the challenge of statistical validation. Nat Rev Clin Oncol 2010;7(6):309-17
10. Pritzker LB, Pritzker KPH. Molecular Signatures as Cancer Biomarkers: Methodologic Issues in Discovery, Validation, Qualification, and Standardization. In: Dakubo G, editor. Field Cancerization: Basic Science And Clinical Applications. Nova Publishers; Hauppauge, New York, USA: 2011. p. 537-57
11. Schulte PA. A conceptual framework for the validation and use of biologic markers. Environ Res 1989;48(2):129-44 (Pubitemid 19102959)
12. Lesko LJ, Zineh I, Huang SM. What is clinical utility and why should we care? Clin Pharmacol Ther 2010;88(6):729-33
13. Pirmohamed M. Acceptance of biomarker-based tests for application in clinical practice: criteria and obstacles. Clin Pharmacol Ther 2010;88(6):862-6
14. Weinstein MC, Skinner JA. Comparative effectiveness and health care spending-implications for reform. N Engl J Med 2010;362(5):460-5
15. Umscheid CA. Maximizing the clinical utility of comparative effectiveness research. Clin Pharmacol Ther 2010;88(6):876-9
16. Teutsch SM, Fielding JE. Comparative effectiveness-looking under the lamppost. JAMA 2011;305(21):2225-6
17. Teutsch SM, Fielding JE. Applying comparative effectiveness research to public and population health initiatives. Health Aff (Millwood) 2011;30(2):349-55
18. Scott MG. When do new biomarkers make economic sense? Scand J Clin Lab Invest Suppl 2010;242:90-5
19. Jain RK, Duda DG, Willett CG, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009;6(6):327-38
20. Bauer DC, Hunter DJ, Abramson SB, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage 2006;14(8):723-7 (Pubitemid 43986366)
21. Duffy MJ. Role of tumor markers in patients with solid cancers: a critical review. Eur J Intern Med 2007;18(3):175-84 (Pubitemid 46628757)
22. Oldenhuis CN, Oosting SF, Gietema JA, de Vries EG. Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer 2008;44(7):946-53
23. Wagner JA, Williams SA, Webster CJ. Biomarkers and surrogate end points for fit-for-purpose development and regulatory evaluation of new drugs. Clin Pharmacol Ther 2007;81(1):104-7 (Pubitemid 46050874)
24. Chau CH, Rixe O, McLeod H, Figg WD. Validation of analytic methods for biomarkers used in drug development. Clin Cancer Res 2008;14(19):5967-76
25. Burns DK. Developing pharmacogenetic evidence throughout clinical development. Clin Pharmacol Ther 2010;88(6):867-70
26. Desai M, Stockbridge N, Temple R. Blood pressure as an example of a biomarker that functions as a surrogate. Aaps J 2006;8(1):E146-52
27. Dalton JE, Kattan MW. Recent advances in evaluating the prognostic value of a marker. Scand J Clin Lab Invest Suppl 2010;242:59-62
28. Liu SV, Melstrom L, Yao K, et al. NeoadjuVant therapy for breast cancer. J Surg Oncol 2010;101(4):283-91
29. Bear HD. NeoadjuVant chemotherapy for operable breast cancer: individualizing locoregional and systemic therapy. Surg Oncol Clin N Am 2010;19(3):607-26
30. Marchio C, Dowsett M, Reis-Filho JS. Revisiting the technical validation of tumour biomarker assays: how to open a Pandora's box. BMC Med 2011;9(1):41
31. Lee JW, DeVanarayan V, Barrett YC, et al. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm Res 2006;23(2):312-28 (Pubitemid 43237862)
32. Downing G. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89-95 (Pubitemid 32225406)
33. De Gruttola VG, Clax P, DeMets DL, et al. Considerations in the evaluation of surrogate endpoints in clinical trials. summary of a National Institutes of Health workshop. Control Clin Trials 2001;22(5):485-502
34. Doust J. Qualification versus validation of biomarkers. Scand J Clin Lab Invest Suppl 2010;242:40-3
35. Kallner A. Measurement performance goals: how they can be estimated and a view to managing them. Scand J Clin Lab Invest Suppl 2010;242:34-9
36. Bossuyt PM. Clinical validity: defining biomarker performance. Scand J Clin Lab Invest Suppl 2010;242:46-52
37. Woodcock J. Assessing the clinical utility of diagnostics used in drug therapy. Clin Pharmacol Ther 2010;88(6):765-73
38. Quinn B. Payers and the assessment of clinical utility for companion diagnostics. Clin Pharmacol Ther 2010;88(6):751-4
39. Ho MK, Goldman D, Heinz A, et al. Breaking barriers in the genomics and pharmacogenetics of drug addiction. Clin Pharmacol Ther 2010;88(6):779-91
40. Taylor JM, Ankerst DP, Andridge RR. Validation of biomarker-based risk prediction models. Clin Cancer Res 2008;14(19):5977-83
41. Ransohoff DF. Rules of evidence for cancer molecular-marker discovery and validation. Nat Rev Cancer 2004;4(4):309-14 (Pubitemid 38525286)
42. Simon R. Development and validation of biomarker classifiers for treatment selection. J Stat Plan Inference 2008;138(2):308-20
43. Reyal F, Van Vliet MH, Armstrong NJ, et al. A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer. Breast Cancer Res 2008;10(6):R93
44. Lucas JE, Carvalho CM, Chen JL, et al. Cross-study projections of genomic biomarkers: an evaluation in cancer genomics. PLoS ONE 2009;4(2):e4523
45. Sole X, Bonifaci N, Lopez-Bigas N, et al. Biological convergence of cancer signatures. PLoS ONE 2009;4(2):e4544
46. Peterson B, George SL. Sample size requirements and length of study for testing interaction in a 2 x k factorial design when time-to-failure is the outcome [corrected]. Control Clin Trials 1993;14(6):511-22 (Pubitemid 24003708)
47. Lathia CD, Amakye D, Dai W, et al. The value, qualification, and regulatory use of surrogate end points in drug development. Clin Pharmacol Ther 2009;86(1):32-43
48. Prentice RL. Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med 1989;8(4):431-40 (Pubitemid 19105891)
49. Prentice RL. Surrogate and mediating endpoints: current status and future directions. J Natl Cancer Inst 2009;101(4):216-17
50. Alonso A, Molenberghs G, Geys H, et al. A unifying approach for surrogate marker validation based on Prentice's criteria. Stat Med 2006;25(2):205-21 (Pubitemid 43141503)
51. Pryseley A, Tilahun A, Alonso A, Molenberghs G. Information-theory based surrogate marker evaluation from several randomized clinical trials with continuous true and binary surrogate endpoints. Clin Trials 2007;4(6):587-97 (Pubitemid 351567515)
52. Alonso A, Molenberghs G. Surrogate marker evaluation from an information theory perspective. Biometrics 2007;63(1):180-6
53. Molenberghs G, Buyse M, Geys H, et al. Statistical challenges in the evaluation of surrogate endpoints in randomized trials. Control Clin Trials 2002;23(6):607-25 (Pubitemid 36005472)
54. Burzykowski T, Buyse M. Surrogate threshold effect: an alternative measure for meta-analytic surrogate endpoint validation. Pharm Stat 2006;5(3):173-86 (Pubitemid 44400217)
55. Collette L, Burzykowski T, Schroder FH. Prostate-specific antigen (PSA) alone is not an appropriate surrogate marker of long-term therapeutic benefit in prostate cancer trials. Eur J Cancer 2006;42(10):1344-50 (Pubitemid 43922404)
56. Hayes DF, Bast RC, Desch CE, et al. Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 1996;88(20):1456-66 (Pubitemid 26340047)
57. Levinson SS. Clinical validation of biomarkers for predicting risk. Adv Clin Chem 2009;48:1-25
58. Levinson SS. Weak associations between prognostic biomarkers and disease in preliminary studies illustrates the breach between statistical significance and diagnostic discrimination. Clin Chim Acta 2010;411(7-8):467-73
59. Hunter DJ, Losina E, Guermazi A, et al. A pathway and approach to biomarker validation and qualification for osteoarthritis clinical trials. Curr Drug Targets 2010;11(5):536-45
60. Mandrekar SJ, Sargent DJ. Clinical trial designs for predictive biomarker validation: theoretical considerations and practical challenges. J Clin Oncol 2009;27(24):4027-34
61. Mandrekar SJ, Sargent DJ. Clinical trial designs for predictive biomarker validation: one size does not fit all. J Biopharm Stat 2009;19(3):530-42
62. Tol J, Punt CJ. Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review. Clin Ther 2010;32(3):437-53
63. Mudd PN Jr, Groenendaal H, Bush MA, Schmith VD. Probabilistic risk analysis: improving early drug development decision making. Clin Pharmacol Ther 2010;88(6):871-5
64. EVans BJ. Establishing clinical utility of pharmacogenetic tests in the post-FDAAA era. Clin Pharmacol Ther 2010;88(6):749-51
65. Kiechle FL, Zhang X, Holland-Staley CA. The -omics era and its impact. Arch Pathol Lab Med 2004;128(12):1337-45 (Pubitemid 39642213)
66. EDRN (Early Detection Research Network). Available from: . cancer.gov/edrn
67. Infectious Disease Biomarker Database (IDBD). Available from: http:// biomarker.cdc.go.kr
68. BioExpress System. Available from: http://www.genelogic.com
69. Integrity. Available from:
70. GioBiom. Available from: :
71. Griss Proteomics Database Engine. Available from:
72. dbCPCO. Available from: www.med . mun.ca/cpco
73. GeneInsight Suite. Available from: pcpgm.partners.org/it-solutions/ geneinsight-suite
74. Aronson SJ, Clark EH, Babb LJ, et al. The geneinsight suite: a platform to support laboratory and provider use of DNA-based genetic testing. Hum Mutat 2011;32(5):532-6
75. Pharmacogenomics KnowledgeBase (PharmGKB). Available from:
76. Sim SC, Altman RB, Ingelman-Sundberg M. Databases in the area of pharmacogenetics. Hum Mutat 2011;32(5):526-31
77. The Pharmacogenetics of Membrane Transporters (PMT) database. Available from:
78. Horvath AR, Kis E, Dobos E. Guidelines for the use of biomarkers: principles, processes and practical considerations. Scand J Clin Lab Invest Suppl 2010;242:109-16
79. Holliday EG, Scott RJ, Attia J. Evidence-based medicine in the era of biomarkers: teaching a new dog old tricks? Clin Pharmacol Ther 2010;88(6):740-2
80. Shen B, Hwang J. The clinical utility of precision medicine: properly assessing the value of emerging diagnostic tests. Clin Pharmacol Ther 2010;88(6):754-6
81. Compton C. Biospecimen Research Network. 2011. Available from:
82. Temple R. Enrichment of clinical study populations. Clin Pharmacol Ther 2010;88(6):774-8
83. Norell H, Zhang Y, McCracken J, et al. CD34-based enrichment of genetically engineered human T cells for clinical use results in dramatically enhanced tumor targeting. Cancer Immunol Immunother 2010;59(6):851-62
84. Becich MJ. The role of the pathologist as tissue refiner and data miner: the impact of functional genomics on the modern pathology laboratory and the critical roles of pathology informatics and bioinformatics. Mol Diagn 2000;5(4):287-99 (Pubitemid 32622201)
85. Biogrid Australia. Available from: http:// www.bio21.org.au
86. Merriel RB, Gibbs P, O'Brien TJ, Hibbert M. BioGrid Australia facilitates collaborative medical and bioinformatics research across hospitals and medical research institutes by linking data from diverse disease and data types. Hum Mutat 2011;32(5):517-25
87. Ptolemy AS, Rifai N. What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema. Scand J Clin Lab Invest Suppl 2010;242:6-14
88. Lindblom A, Robinson PN. Bioinformatics for human genetics: promises and challenges. Hum Mutat 2011;32(5):495-500
89. Ioannidis JP, Panagiotou OA. Comparison of effect sizes associated with biomarkers reported in highly cited individual articles and in subsequent meta-analyses. JAMA 2011;305(21):2200-10
90. Bossuyt PM. The thin line between hope and hype in biomarker research. JAMA 2011;305(21):2229-30
91. Pritzker KP. Cancer biomarkers: easier said than done. Clin Chem 2002;48(8):1147-50 (Pubitemid 34809818)
92. Pritzker KP, Azad A. Genomic biomarkers for cancer assessment: implementation challenges for laboratory practice. Clin Biochem 2004;37(7):642-6 (Pubitemid 38845026)
93. Ransohoff DF, Gourlay ML. Sources of bias in specimens for research about molecular markers for cancer. J Clin Oncol 2010;28(4):698-704
94. Silberman S. Libraries of the flesh. Wired; 2010
95. Juhl H. Preanalytical aspects: a neglected issue. Scand J Clin Lab Invest Suppl 2010;242:63-5
96. Price CP, Martin L. Novel markers, a payer's perspective: commissioning a new service. Scand J Clin Lab Invest Suppl 2010;242:103-8
97. Timm J, Renly S, Farkash A. Large Scale Healthcare Data Integration and Analysis using the Semantic Web. Stud Health Technol Inform 2011;169:729-33
98. Gombocz Eas RA, Eshleman JA, Zack Rhoades Z. From multiple biomarkers to patient-centric personalized medicine: An "Applied Semantic Knowledgebase" for decision support. 2010. Available from: