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Biomarkers glossary & taxonomy
Evolving Terminologies for Emerging Technologies
Comments? Questions? Revisions? Mary Chitty 
mchitty@healthtech.com
Last revised November 25, 2014

 



Drug discovery & development Map: Finding guide to terms in these glossaries  Glossaries & Taxonomies Site Map  Related glossaries include  Cancer   Drug safety   Metabolic profiling   Molecular diagnostics   Molecular Imaging  Molecular Medicine  Pharmacogenomics    SNPs & other Genetic Variations

biomarker:
A characteristic that is measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses. M. Danhof, Meeting Report, Markers of pharmacological and toxocological action, BioMedCentral, 2001  http://www.biomedcentral.com/abstracts/CRP/1/023/

 
accessible biomarkers:
A biomarker that can be obtained in a minimally invasive manner, typically from blood, plasma, serum, saliva or urine.  Google = about 42 Oct. 25, 2004, about 78 Oct. 3, 2005, about 424 Dec 9, 2008; about 1, 100 Dec 7, 2009

antecedent biomarkers: Most adult-onset degenerative diseases of the nervous system are likely to be a composite of related characteristics, heritable and environmental. The correlated combinations of these features constitute the trait or disease. Therefore, these types of antecedent biomarkers may or may not be directly involved in the etiology. In some instances the genetic variant is neither necessary nor sufficient to cause the disease. However, they can be powerful antecedents at any stage of the disease pathway ... By definition these antecedent biomarkers exist before the disease or the outcome occurs and are independent of other exposures. They improve the precision in the measurement of other associations, because they may be synergistic or antagonistic. Biomarkers: Potential Uses and Limitations, Richard Mayeux, NeuroRx. 2004 April; 1(2): 182–188

Biomarkers that exist before signs of a disease are present.   See also under biological markers   Google = about 37 Oct. 25, 2004, about 207 Oct. 3, 2005, about 707 Dec 9, 2008; about 1,960 Dec 7, 2009

biochemical biomarkers:  Biochemical biomarkers have long contributed to the assessment of risk and benefits in cancer, and routine clinical assays are available.  Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003 Google = about 454 Nov. 9, 2004, about 539 Oct. 3, 2005; about 14,400 Dec 7, 2009

biological marker (biomarker): A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126957.pdf    biomarker (medicine): Wikipedia http://en.wikipedia.org/wiki/Biomarker_(medicine) 

biological markers:  Measurable and quantifiable biological parameters (e.g. specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health - and physiology related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. MeSH, 1989 

 1. Parameter that can be used to identify a toxic effect in an individual organism and can be used in extrapolation between species. 2. Indicator signalling an event or condition in a biological system or sample and giving a measure of exposure, effect, or susceptibility.  IUPAC Toxicology

Google = about 10,900 Aug. 6, 2002; about 24,800 Aug. 18, 2003; about 84,000 Oct. 25, 2004, about 904,000 Oct. 3, 2005, about 1,260,.000 Dec 9, 2008; about 491,000 Dec 7 2009
Related/synonymous? terms: biomarkers, genetic markers, protein biomarkers, surrogate markers; Broader term: markers  Narrower term: genomic biomarkers

biological tumor markers: Cancer genomics  Google = about 30 Aug. 6, 2002; about 59 Aug. 18, 2003; about 194 Oct. 25, 2004; about 275 Oct. 11, 2005, about 7,930 Dec 9, 2008; about 823,000 Dec 7, 2009

biomarker analytes: DNA, gene expression profiles, protein[s], protein expression, metabolite[s], cells or combinations of these can constitute biomarkers. Google = about 15 Oct. 25, 2004, about 30 Oct. 3, 2005, about 94 Dec 9, 2008; about 974 Dec 7, 2009

biomarker assays: 

biomarker commercialization: Biomarkers feature in thousands of published articles each year, evidencing the high level of interest and research in this field. This report focuses on issues that must be addressed to utilize this growing knowledge about biomarkers and successfully commercialize them in therapeutic and diagnostic applications.  Commercializing Biomarkers in Therapeutic and Diagnostic Applications May 2011 Table of Contents | Tables and Figures |Executive Summary
 

biomarker guidelines: The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and Drug Administration (FDA) guidance documents, and conducted a survey of investigators to determine practices and challenges to executing biomarker studies in clinical trials of new drugs in early development. This document provides standard definitions and categories of biomarkers, and lists recommendations to sponsors and investigators for biomarker incorporation into such trials. Our recommendations for sponsors focus on the identification and prioritization of biomarkers and assays, the coordination of activities for the development and use of assays, and for operational activities. We also provide recommendations for investigators developing clinical trials with biomarker studies for scientific rationale, assay criteria, trial design, and analysis. Guidelines for the Development and Incorporation of Biomarker Studies in Early Clinical Trials of Novel Agents,  Dancey JE, et. al,  Clin Cancer Res. 2010 Mar 9. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/20215558

biomarker validation: An important distinction is between biomarker validation and [biomarker] qualification, where validation is the process of assessing the assay or measurement performance characteristics and qualification is evidentiary process of linking a biomarker with biology and clinical endpoints.  J. Wagner, Merck, Asilomar Conference on Biomarkers Discovery and Validation, Oct. 14-18,  2004 http://bigdaddy.scripps.edu/darlene/Asilomar/pages/abstracts/jwagner.htm   See also under valid biomarker and  validation- biomarker

biomarkers:  Anatomic, physiologic, biochemical, or molecular parameters associated with the presence and severity of specific disease states. Biomarkers are detectable and measurable by a variety of methods including physical examination, laboratory assays and medical imaging.   Massachusetts General Hospital, Center for Biomarkers in Imaging, 2004 http://www.biomarkers.org/NewFiles/faqs/definition.html#Anchor-What-35882 

Biomarkers may be any parameter of a patient that can be measured, for example, mRNA expression profiles, proteins, proteomic patterns, lipids, imaging methods, or electrical signals. The best biomarkers are accurate, relatively noninvasive and easy-to-perform tests that can be done at the bedside or in the outpatient setting. These tests involve a blood or spot urine specimen, can be measured serially, and have a fast turnaround. In the past, most efforts had focused on discovering tissue and urinary biomarkers. However, there has been a recent shift to finding serum biomarkers (11), with new methods and technologies making this more practical. Stephen M. Hewitt*, James Dear and Robert A. Star, Discovery of Protein Biomarkers for Renal Diseases, J Am Soc Nephrology 15:1677-1689, 2004  http://jasn.asnjournals.org/cgi/content/full/15/7/1677 

Typically, “biomarker” is defined as a laboratory measurement that reflects the activity of a disease process. There are many such markers identified for many diseases of the nervous system, for example, various magnetic resonance imaging (MRI) measures in multiple sclerosis and Alzheimer’s disease treatments, positron emission tomographic (PET) scanning of dopamine transporters in Parkinson’s disease, etc.14 In essentially all cases, these markers quantitatively correlate (either directly or inversely) with disease progression. Russell Katz, Biomarkers and Surrogate Markers: An FDA Perspective, NeuroRx 1(2): 189-195, April 2004  http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=534924  

A characteristic that is measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses. M. Danhof, Meeting Report, Markers of pharmacological and toxocological action, BioMedCentral, 2001  http://www.biomedcentral.com/abstracts/CRP/1/023/ 
Wikipedia: biomarker
http://en.wikipedia.org/wiki/Biomarker 
Google = about 70,300 Aug. 6, 2002; about 182,000 Aug. 18, 2003, about 430,000 Oct. 25, 2004, about 3,960,000 Oct. 3, 2005; about 4,810,000 Nov 14. 2006, about 3,600,000 Dec 9, 2008; about 1,180,.000 Dec 7, 2009 [are these numbers right?]  Narrower terms: genetic biomarkers, genomic biomarkers, high-impact biomarkers, protein biomarkers, proteomic biomarkers Related/synonymous? terms:  biological markers, genetic markers, surrogate markers.  Broader term: markers

biomarker commercialization:  Biomarkers can be valuable tools in clinical diagnostics as well as in therapeutic discovery and development. They can be used to predict response to therapy or risk of side effects for personalized medicine applications. Additional types include predisposition, screening, diagnostic, prognostic, toxicity, pharmacodynamic, and other biomarkers.  Commercializing Biomarkers in Therapeutic and Diagnostic Applications: From Development to Validated Product focuses on questions that must be addressed to successfully take advantage of the potential of biomarkers.  Commercializing Biomarkers in Therapeutics and Diagnostic Applications May 2011 Table of Contents | Tables and Figures

Biomarkers Consortium: A public-private biomedical research partnership of the Foundation for the National Institutes of Health, Inc. that involves a variety of public and private stakeholders including the National Institutes of Health (NIH); Food and Drug Administration (FDA); Centers for Medicare & Medicaid Services (CMS); the pharmaceutical, biotechnology, diagnostics, and medical device industries; non-profit organizations and associations; and advocacy groups. http://www.fnih.org/work/key-initiatives/biomarkers-consortium

Despite the challenges overcome by this project, the most important lesson learned is that cross-company precompetitive collaboration is a feasible robust approach to biomarker qualification. The Biomarkers Consortium: practice and pitfalls of open-source precompetitive collaboration. Wagner JA et. al Clin Pharmacol Ther. 2010 May;87(5): 539-542.  http://www.ncbi.nlm.nih.gov/pubmed/20407460

biosignatures: Analyzing patterns of protein expression from tissues or fluids over the course of disease progression could reveal proteome- level "biosignatures" indicative of specific disease status. Such "biosignatures" may be used extensively in 21st century medical diagnostics. Similarly, analyses of protein profiles before and after pharmacological treatments could provide vital clues regarding drug effectiveness and toxicity. In addition, particular "biosignatures" may be used to customize therapeutic strategies for individual patients. [National Heart, Lung, and Blood Institute, Proteomics Initiative, Sept. 5, 2001, RFP/BAA: BAA-02-04] http://grants1.nih.gov/grants/guide/notice-files/NOT-HL-02-004.html

Wikipedia http://en.wikipedia.org/wiki/Biosignature   Google = about 879 Aug. 6, 2002; about 1,740 Aug. 18, 2003; about 4,110 Oct. 25, 2004, about 34,500 Oct. 3, 2005; about 68,700 Nov 14, 2006, about 77,500 Dec. 9, 2008; about 23,200 Dec 7, 2009  Related term: protein biomarkers

bridging biomarkers: Biomarkers of cellular injury that can link laboratory findings directly to human outcomes.  A biomarker for a given analyte or set of analytes that can be applied in both a pre- clinical and clinical setting.  Google = about 65 Oct. 25, 2004, about 154 Oct. 3, 2005; about 214 Nov 14, 2006, about 454 Dec 9, 2008; about 743 Dec 7, 2009

CDISC Clinical Data Interchange Standards Consortium: Regulatory Affairs

Cancer  Biomarkers: Adoption is driving growth report: Products, applications & markets, standards of care, improved screening & early detection, business model profiles, market projections, Insight Pharma Reports,  2008   
Google = about 4,750 Oct. 25, 2004; about 61,200 Oct. 11, 2005; about 108,000 Nov 14, 2006, about 128,000 Dec 9, 2008; about 112,000 Dec 7, 2009

cancer molecular markers:  Cancer Molecular MarkersCancer Molecular Markers February 10-12, 2014 • San Francisco, CA Program | Register | Download Brochure 
See also Cancer genomics & diagnostics


Molecular Biomarkers for Cancer Detection and Management July 2013 Table of Contents | Tables and Figures
cellular biomarkers:
Fundamental to many tissue- engineered devices are problems of inflammation associated with how biological cells respond to a given device when inserted into the body. ... To assure that tissue- engineered materials are free of molecular changes that could occur during the in vitro development phase, cellular biomarkers are being identified that can be used during the manufacturing process. H. Rodriguez, Cellular Biomarkers Used to Detect Damage in Tissue- Engineered Medical Products, Society for Biomaterials,  May 01, 2002, Technipubs, Recent Publications by NIST authors http://www.nist.gov/manuscript-publication-search.cfm?pub_id=830298  
Wikipedia biomarker (cell)
http://en.wikipedia.org/wiki/Biomarker_(cell)    Google = about 469 Oct. 25, 2004; about 544 Oct. 11, 2005; about 766 Nov 14, 2006, about 5,800 Dec 9, 2008; about 11,900 Dec 7, 2009

cell specific biomarkers: Using biomarkers linked to distinct, defined cell types and tissues provides a direct link to histopathology without its drawbacks, plus it provides increased sensitivity, and specificity. ...  Serum creatinine is the most widely used renal biomarker in spite of its known shortcomings. Cell-specific biomarkers are more specific and sensitive and have been known for over 40 years, but they are still underused in renal medicine and research. In particular, while many studies have shown cell-specific biomarkers to be valuable in diagnosis, there are few studies where they have been used to guide therapy or linked to quantitative changes in the kidney. Cell-specific biomarkers in renal medicine and research, Shaw M. Methods Mol Biol. 2010;641:271-302. http://www.ncbi.nlm.nih.gov/pubmed/20407953

chemical biomarkers:  Chemical biomarkers released by the host in response to invasion and infection could provide a target for antibody arrays, mass spectrometry, and other analytical techniques to diagnose infection. In spite of these advances, general research into the biochemistry of agents and the rapid identification of pathogenicity of agents is still needed. National Security and Homeland Defense: Challenges for the Chemical Sciences in the 21st Century, National Academies Press, 2003 http://www.nap.edu/openbook.php?record_id=10543&page=26  Google = about 136 Aug. 6, 2002; about 230 Aug. 18, 2003l; about 319 Sept. 2, 2004; about 432 Oct. 11, 2005; about 718 Nov 14, 2006, about 3,120 Dec 9, 2008; about 8,510 Dec 7, 2009

clinical biomarkers:  Google = about 22,000 Nov 14, 2006; about 29,300 June 25, 200, about 13,600 Dec 9, 2008; about 64,300 Dec 7, 2009

clinical endpoint: A characteristic or variable that reflects how a patient feels, functions or survives. Biomarkers Definition Working Group, 1998, Gregory Downing, NIH Initiatives in Surrogate Endpoints and Endpoint Analysis,  Nonclinical Studies Subcommittee, Advisory Committee for Pharmaceutical Science presentation, 2000  http://www.fda.gov/ohrms/dockets/ac/00/slides/3593S1_03_downing.ppt 

clinical pharmacometabolomics:  The segregation of patient populations using small molecule biomarkers in clinical trials, adverse drug reaction, and drug efficacy evaluation.  Phenomenome Discoveries http://www.phenomenome.com/  Broader term: pharmacometabolomics

combination biomarkers: Biomarkers that are based on more than one category of analytes. (Alternatively: Integrative biomarkers, Systems biology biomarkers)  Google = about 22, Oct. 25, 2004; about 40 Oct. 11, 2005; about 55 Nov 14, 2006, about 198 Dec. 9, 2008; about 642 Dec 7, 2009  Related/narrower terms: DNA markers, genetic biomarkers, genomic biomarkers, metabolic biomarkers, metabolite biomarkers,  metabolomic biomarkers, protein biomarkers, proteomic biomarkers

diagnostic biomarkers: May span a continuum from early to more advanced disease manifestations. May be used as synonymous with disease biomarkers. See also under biological biomarkers  Google = about 633 Oct. 25, 2004, about 25,700 Nov 14, 2006, about 17,600 Dec 9, 2008; about 61,100 Dec 7, 2009  Narrower terms: disease onset biomarkers, monitoring biomarkers, occurrence biomarker, staging biomarkers  Related terms:  Molecular Diagnostics

direct biomarkers: See under indirect biomarkers  Google = about 39 Oct. 11, 2005; about 85 Nov 14, 2006, about 326 Dec 9, 2008; about 857 Dec 7, 2009

disease biomarkers: The goal of this initiative is to validate biomarkers for well-defined human diseases of liver, kidney, urological tract, digestive and hematologic systems, and endocrine and metabolic disorders, diabetes and its complications, and obesity, for which there are no or very few biomarkers, or for which standard biomarkers are currently prohibitively invasive or expensive. New biomarkers will stimulate bench to bedside translation by providing measures of the biological effects of potential new treatments. The ideal biomarker can be measured in a minimally invasive way, can be measured repeatedly over time, identifies early stages of disease, is indicative of disease prognosis, and correlates well with progression and response to therapy. Especially of interest would be studies designed to test the validity of candidate biomarkers or new technologies to monitor candidate biomarkers in patient tissue samples or small groups of well-characterized patients. Development of disease biomarkers, NIH PA-05-098, Release Date: April 27, 2005 http://grants.nih.gov/grants/guide/pa-files/PA-05-098.html#PartI 

Biomarkers of disease: cover measurement of endogenous substances or parameters indicative of a disease process and the use of pharmacodynamic and genetic markers in evidence- based laboratory medicine and treatment (markers of efficacy). Biomarkers, Taylor & Francis, Aims & Scope http://www.tandf.co.uk/journals/titles/1354750x.asp 

Disease-related biomarkers are not a new phenomenon. Early examples include blood glucose for diabetes diagnosis and management and cholesterol for cardiovascular risk. However, introduction of DNA microarrays in the mid-1990s enabled a revolution in transcriptomics and triggered a major paradigm shift in the way life scientists approached research. Subsequently, metabolomics and metabonomics, applied mainly to safety-related biomarkers originally, began to turn to disease-related biomarkers.  Disease Related Biomarkers: Their potential in patient screening, prognosis and stratification, Insight Pharma Reports 2007 

disease markers: Nature Disease Markers archives http://www.nature.com/nrcardio/archive/subject_cardio_s8_092013.html
Disease Markers,  Hindawi http://www.hindawi.com/journals/dm/   Google = about 5,260 Aug. 18, 2003; about 15,600 Sept. 2, 2004, about 115,000 Oct. 3, 2005; about 47,200 Nov 14, 2006, about 311,000 Dec 9, 2008; about 98,800 Dec 7, 2009 
Narrower terms: disease risk biomarkers, disease onset biomarkers, monitoring biomarkers, occurrence biomarkers, staging biomarkers

disease onset biomarkers:  Reports onset of disease, prior to clear symptomatic evidence. Identification of such biomarkers will be quite difficult, because confirmation of disease onset will occur later, but require access to earlier samples. Google = about 5 Oct. 25, 2004, about 5, Oct. 3, 2005; about 7 Nov 14, 2006. about 10 Dec 9, 2008; about 9 Dec 7, 2009

disease risk biomarkers:  Typically based on DNA, in some cases disease occurrence is uncertain, in others timing of disease onset is uncertain.  Google = about 16 Oct. 25, 2004, about 42 Oct. 3, 2005; about 58 Nov 14, 2006, about 206 Dec 9, 2008; about 30,900 Dec 7, 2009  Related/synonymous? term: antecedent biomarkers

DNA marker:  A cloned chromosomal locus with allelic variation that can be followed directly by a DNA- based assay such as Southern blotting or PCR. NHLBI  Google = about  6,100 Aug. 6, 2002; about 10,900 Aug. 18, 2003; about 22,000 Sept. 2, 2004; about 389,000 Nov. 14, 2006, about 1,220,000 Dec 9, 2008; about 238,000 Dec 7, 2009

Google = about 134 Nov 14, 2006, about 800 Dec 9, 2008; about 13,500 Dec 7, 2009  Narrower terms: bridging biomarkers, efficacy biomarkers, exclusion biomarkers, inclusion biomarkers, safety biomarkers, target biomarkers, toxicity biomarkers

efficacy biomarkers: In oncology, a special class of extensively evaluated biomarkers of efficacy (surrogate endpoints) that generally correlate with desired clinical outcomes can be used as a basis for corporate decisions as well as for gaining accelerated provisional regulatory approval of a drug. E. Floyd, TM McShane, Development and Use of Biomarkers in Oncology Drug Development, Toxicol Pathol. 32 (Supplement 1) 106- 115, 2004

A biomarker that reflects beneficial effect of a given treatment. (May be simply reversal of a disease biomarker.)  Google = about 142 Sept. 2, 2004; about 216 Oct. 11, 2005, 747 Nov 14, 2006, about 1,700 Dec 9, 2008; about 30,100 Dec 7, 2009

exclusion biomarkers: A biomarker that predicts that a given treatment will produce an adverse response.  Could be used to exclude patients from clinical trials. Google = about 15 Dec 7, 2000 

exploratory biomarkers: Biomarkers based on general exploratory or research information, such as broad gene expression screening, or collection of sera or tissue samples, and that has not reached the status of a probable valid biomarker. Insight pharma Reports, Biomarkers in Clinical Development: Implications for Personalized Medicine and Streamlining R&D Insight Pharma Report, 2005  Google = about 14,500 Dec 7, 2009

exposure biomarkers: covering detection and measurement of internal exposure to drugs and other chemicals. Biomarkers, Informa, Aims & Scope http://informahealthcare.com/page/Description?journalCode=bmk   Google = about 23,900 Nov 14, 2006, about 10,300 Dec 9, 2008; about 23,900 Dec 7, 2009

Extracellular Biomarkers Summit
Extracellular Biomarkers Summit March 16-18, 2015 • Cambridge, MA Program | Register | Download Brochure

genetic biomarkers: A single gene (DNA) for which a mutation, deletion, SNP or some other feature provides predictive value. Google = about 680 Sept. 2, 2004; about 10,300 Oct. 11, 2005; about 18,700 Nov 14, 2006, about 13,000 Dec 9, 2008; about 48,500 Dec 7, 2009

genetic markers:  A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event MeSH, 1989

Consist of specific nucleotide patterns. NHLBI  Google = about 40,200 Aug. 6, 2002; about 87,100 Aug. 18, 2003; about 142,000 Sept. 2, 2004; about 1,470,000 Oct. 11, 2005;  about 1,200,000 Nov 14, 2006, about 1,080,000 Dec 9, 2008; about 368,000 Dec 7, 2009 Related term: ESTs Gene definitions UniGene (database) has marker information
Wikipedia: genetic marker
http://en.wikipedia.org/wiki/Genetic_marker 

genetic variation: SNPs & other genetic variations

genomic biomarkers: A measurable DNA or RNA characteristic that is an indicator of normal biologic processes, pathogenic processes, and/or response to therapeutic or other inventions.    could, for example, reflect: The expression of a gene, The function of a gene, The regulation of a gene ... does not include the measurement and characterisation of proteins or low molecular weight metabolite. DNA characteristics include, but are not limited to Single Nucleotide Polymorphisms (SNPs), Variability of short sequence repeats, DNA modification, e.g. methylation, Insertions, Deletions, Copy number variation, Cytogenetic rearrangements, e.g. translations, duplications, deletions or inversions.  RNA characteristics include, but are not limited to RNA sequence, RNA expression levels, RNA processing, e.g. splicing and editing, MicroRNA levels. E15 terminology in Pharmacogenomics, ICH 2008 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073162.pdf 

Using genomic biomarkers in drug and diagnostic development and regulatory decision making is showing a lot of potential, but still requires more qualification and validation. We have identified two key application areas First, at the drug discovery stage, genomic biomarkers applied to compound profiling offer efficacy and toxicity data, allowing better decision making at earlier stages and reducing late-stage attrition. Second, in the clinical setting, genomic biomarkers have the promise in disease diagnosis/ prognosis; treatment, patient, or dose selection; and clinical safety and efficacy assessment.  A gene expression pattern (RNAs) that is able to discriminate or predict.  Google = about 579 Sept. 2, 2004; about 9,280 Oct. 11, 2005, about 14,400 April 24, 2006, about 15,300 Nov 14, 2006; about 16,400 Apr 6, 2007, about 12,400 Dec 9, 2008; about 35,300 Dec 7, 2009

Table of Pharmacogenomic Biomarkers in Drug Labels, FDA, 2011 http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm  

genotypic biomarkers: The cytochrome P450 (CYP) system of drug metabolising enzymes represents the best studied set of pharmaceutically important genotypic markers. Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003  Google = about 41 Oct. 11 2005, about 42 Nov 14, 2006, about 122 Dec 9, 2008; about 492 Dec 7, 2009

haplotype biomarkers: Because haplotypes include the linkage of multiple SNPs, they will generally occur at lower prevalence than individual gene variants, and the more SNPs involved in a haplotype, the narrower and more precisely defined will be the patient subgroups. Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003   Google = about 3 Dec 7, 2009

high-impact biomarkers: pragmatic, high-priority areas of opportunity for biomarker identification, development, and qualification that promise to expedite therapeutic development and improve patient diagnosis, care, and treatment.  Biomarkers Consortium press release, 2008 http://www.biomarkersconsortium.org/index.php?option=com_content&task=view&id=109&Itemid=61 

"ideal" biomarkers:  Should have high sensitivity and specificity as well as high predictive value for disease, be easy to obtain through noninvasive procedures, and be easy to measure with precision and accuracy. Executive Summary, DIET, DNA METHYLATION PROCESSES AND HEALTH WORKSHOP, National Cancer Institute, Aug. 2001 http://prevention.cancer.gov/files/news-events/20010806-8e.pdf    Google = about 60 Nov. 5, 2004; about 139 Oct. 11, 2005; about 239 Nov 14, 2006, about 720 Dec 9, 2008; about 1,430 Dec 7, 2009

imaging biomarkers: The term biomarker is often associated with the detection or measurement (in vitro) of expressed genes, proteins, or metabolites in biological fluids. To drug developers, however, biomarker can refer equally well to morphological, functional, or molecular measurements made in vivo using medical imaging equipment, such as: Computed tomography (CT) Magnetic resonance imaging (MRI) Positron emission tomography (PET) Ultrasound and Optical scanners Molecular Imaging in Drug R&D and Medical Practice: Techno9logies, Applications, Markets, Insight Pharma Reports, 2008 http://www.insightpharmareports.com/reports/2008/92_Molecular_Imaging/overview.asp

inclusion biomarkers: A biomarker that predicts that a given treatment will produce a positive response. Google = about 4 Sept. 2, 2004; about 7 Oct. 11, 2005, about 21, Nov 14, 2006, about 56 Dec 9, 2008; about 61 Dec 7, 2009

indirect biomarkers: Biomarkers are very useful tools when the metabolic fate of the compound or the etiology of a resultant disease is completely understood. They may contribute to confusion if it is not possible to distinguish between markers of exposure and markers of disease. Such is the case for biomarkers used in the assessment of diisocyanate exposure. Biomarkers for diisocyanate exposure result from both direct and indirect effects. Molecules such as hemoglobin, albumin, tubulin, glutathione, and laminin have been implicated as having been directly modified as a result of exposure to toluene diisocyanate (TDI). In addition, indirect biomarkers have included profiles of molecules such as antibodies, cytokines, cell accumulation or proliferation, and markers of oxidative stress. WE Brown, AL Burkert, Biomarkers of toluene diisocyanate exposure Appl Occup Environ Hyg. 17(12): 840-845, Dec. 2002 Google = 148 about  Oct. 21, 2005, 295 Nov 14, 2006, about 977 Dec 9, 2008; about 2,850 Dec 7, 2009

kidney biomarkers: In May 2008, the FDA and EMEA confirmed their joint review and acceptance of seven new laboratory tests on urine which signal kidney injury. The protein signals, known as biomarkers, were confirmed in data from rat studies submitted to the FDA and EMEA by the PSTC. The FDA and EMEA jointly came to the conclusion that: the kidney biomarkers are acceptable in the context of non-clinical drug development for the detection of acute drug-induced kidney toxicity; the kidney biomarkers provide additional and complementary information to the currently available standards; the use of kidney biomarkers in clinical trials is to be considered on a case-by-case basis in order to gather further data to qualify their usefulness in monitoring drug-induced kidney toxicity in man. Predictive Safety Testing Consortium PSTC, Critical Path Institute  http://www.c-path.org/pstc.cfm  

kidney safety biomarkers: An illustrative and "door opening" safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the "know how" acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. Impact of biomarker development on drug safety assessment, Marrer E, Dieterle F. Toxicol Appl Pharmacol. 2010 Mar 1;243(2):167-79. Epub 2009 Dec 28. http://www.ncbi.nlm.nih.gov/pubmed/20036272   

Also known as renal safety biomarkers.

known valid biomarker:  A biomarker that is measured in an analytical test system with well established performance characteristics and for which there is widespread agreement in the medical or scientific community about the physiologic, toxicologic, pharmacologic, or clinical significance of the results. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

marker vaccines: Vaccines used in conjunction with diagnostic tests to differentiate vaccinated animals from carrier animals. Marker vaccines can be either a subunit or a gene- deleted vaccine. MeSH, 2001

markers: SNPs & Genetic Variations  Types of genetic maps are differentiated largely by the type of marker used. 
Google  markers biotechnology = about 52,100 Aug. 6, 2002; about 112,000 Aug. 18, 2003 about 171,000 Sept. 2, 2004 markers pharmaceutical = about 129,000 Sept. 2, 2004

Narrower terms: biological markers, biomarkers, DNA markers, ESTs, genetic markers, polymorphisms; SNPs & Genetic Variations DNA fingerprints, microsatellite markers, microsatellite repeats, microsatellites,  minisatellite repeats, RFLPs, restriction enzymes, SSRs, STRs, STSs, satellites Related terms: Maps- genomic & genetic  

mechanism based biomarkers: Biomarkers whose activity is mediated through the theoretical disease mechanism of action. Cambridge Healthtech Advisors, Biomarkers in Clinical Development: Implications for Personalized Medicine and Streamlining R&D report, 2005

mechanistic markers: changes in the subcellular phenotype of the organism can lead to alterations in proteins detectable as markers. These changes, constituting mechanistic markers, are closely reflective of what is going on in the cell and how the signaling pathways are manipulated. Proteomics-based Development of Biomarkers in Cardiovascular Disease Mechanistic, Clinical, and Therapeutic Insights Manuel Mayr et al., Molecular & Cellular Proteomics 5:1853-1864, 2006. http://www.mcponline.org/cgi/content/full/5/10/1853?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=3570&resourcetype=HWFIG

metabolic biomarkers: At the non-clinical stage, metabolic biomarkers provide early profiles on drug efficacy, toxicity and mechanism, thus allowing more informed lead candidate selection. Many of these markers can be translated into the clinic, offering exploratory biomarkers of safety, efficacy, tolerability and pharmacodynamics. Metabolic biomarkers may also prove useful in advancing personalized medicine by allowing patient stratification and more effective clinical trial design. Google = about 143 Oct. 25, 2004, about 973 Nov 14, 2006; about 11,000 Apr 6, 200. about 5,770 Dec 9, 2008; about 18,900 Dec 7, 2009 Related terms: Metabolic profiling & engineering

metabolite biomarkers: Individual metabolites have already been used as disease biomarkers for years. ... Metabolomics enables the identification of biomarkers based on entire groupings of metabolites that are up- or downregulated in unison under specific conditions.  Charles W. Schmidt,  Metabolomics, What's happening downstream of DNA, Metabolite Biomarkers, Medscape, posted 6/1/2004   http://www.medscape.com/viewarticle/478878_3 

A single metabolite for which presence or expression level is significant.  Google = about 156 Oct. 25, 2004, about 126 Oct. 11, 2005, 352 Nov 14, 2006, about 1,000 Dec 9, 2008; about 3,000 Dec 7, 2009

metabolomic biomarkers: 
A pattern of metabolites that is able to discriminate or predict. Google = about 16 Oct. 25, 2004; about 304 Oct. 11, 2005, about 578 Nov 14,  2006; about 860 Dec 9, 2008; about 3,220 Dec 7, 2009
Metabolomic biomarkers: Their Role in the Critical Path, 2009 http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/ArticlesandPresentations/ucm077544.htm 

miRNA biomarkers: microRNA as Biomarkers and DiagnosticsmicroRNA as Biomarkers and Diagnostics March 17-18, 2014 • Boston, MA

Program | Register | Download Brochure

Scientists at the Institute of Systems Biology report that research has shown that circulating miRNAs might serve as biomarkers for liver damage caused by drugs such as acetaminophen.  Genetic Engineering News, 2009 http://www.genengnews.com/genCasts.aspx?id=254  Google = about 6,860 Dec 8, 2009

molecular markers: The three most common types of markers used today are RFLP, RAPD and isozymes.  The classes of molecular markers, Mapping plant genomes with molecular markers, Phillip McClean, 1998  http://www.ndsu.nodak.edu/instruct/mcclean/plsc731/mapping/mapping1.htm 

Seems also to be an umbrella term for most of the terms in this glossary.  Google = about 31,100 Aug. 6, 2002; about 65,600 Aug. 18, 2003; about 122,000 Sept. 2, 2004, about 1,120,000 Nov 14, 2006, about 885,000 Dec 9, 2008; about 349,000 Dec 7, 2009
Wikipedia: molecular marker
http://en.wikipedia.org/wiki/Molecular_marker 

monitoring biomarkers: Reports reoccurrence or progression of disease.  Google = about 180 Sept. 2, 2004; about 213 Oct. 11, 2005, about 456 Nov 14, 2006, about 2,310 Dec 9, 2008; about 3,400 Dec 7, 2009

mRNA biomarkers: In medicine, mRNA transcripts are being developed as molecular biomarkers for the diagnosis and treatment of a number of diseases. These biomarkers offer early and more accurate prediction and diagnosis of disease and disease progression, and ability to identify individuals at risk. Use of microarrays also offers opportunity to identify orthogonal (uncorrelated) biomarkers not known to be linked with conventional biomarkers. mRNA transcripts as molecular biomarkers in medicine and nutrition, Roger Sundee, Journal of Nutritional Biochemistry doi:10.1016/j.jnutbio.2009.11.012  http://www.jnutbio.com/article/S0955-2863(10)00006-9/abstract  Google = about 2,940 Dec 7, 2009

multiple biomarkers: A common statement -- A single biomarker will not be good enough to predict outcome, but combinations of biomarkers will be better at predicting outcome because each biomarker may represent a different aspect of the disease process.  Jeremy Taylor, Statistical Issues in Cancer Biomarker Assessment, Dept. of Biostatistics, Univ. of Michigan, 2004  http://mbi.osu.edu/2004/ws5materials/taylor.pdf  Google = about 9,420 Oct. 11, 2005, about 23,500 Nov 14, 2006, about 19,700 Dec 9, 2008; about 53,900 Dec 7, 2009

multivariate markers: Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker’s diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease  Christian Habeck, PhD,A Norman L. Foster, MD,B Robert Perneczky, MD,C Alexander Kurz, MD,C Panagiotis Alexopoulos, MD,CD Robert A. Koeppe, PhD,E Alexander Drzezga, MD,F and Yaakov Stern, PhDA  Neuroimage. 2008 May 1; 40(4): 1503–1515.

We propose a general theory of phenotyping based on broadly distributed multivariate markers as the metrics of classification and standard pattern recognition algorithms as the method of class discovery.  RE Mare, Phenotyping neurons with pattern recognition of molecular mixtures Signal Processing and Its Applications, 2003. Proceedings. Seventh International Symposium 1: 689 - 692, 1 - 4 July 2003  http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=1224797   
Google = about 38 Sept. 2, 2004; about 58 Oct. 11 2005, about 55 Nov 14, 2006, about 95 Dec 9, 2008, about 270 Oct 13, 2009 

occurrence biomarkers: Reports an acute disorder.  Google = about 7 Oct. 25, 2004; about 9, Oct. 11, 2005, 0 Dec 9, 2008; about 8 Dec 7 2009

pharmacodynamic biomarkers: Pharmacodynamic biomarkers for molecular cancer therapeutics, D. Sarker and P Workman, Advances in Cancer Research 96: 213-268, 2007  
Google = about 73 Oct. 25, 2004; about 148 Oct. 11, 2005, about 819 Nov 14, 2006, about 3,108 Nov 9, 2008; about 22,500 Dec 7, 2009

pharmacogenomics biomarkers: the importance of pharmacogenomics markers has been demonstrated through the correlation of specific genetic variations in the CYP450 family. See under genomic biomarkers

pharmacological biomarkers: Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).  MeSH 2008  See also Drug safety, pharmacovigilance & toxicology glossary & taxonomy

physiological biomarkers: Various physiological responses have been measured and utilized as biomarkers.  These include studies of such basic physiological functions as respiration, changes in growth rate, feeding, excretion, etc.  Physiological responses are used to provide integrated measures of an organisms well-being, based on a range of different functional attributes. An example of one such measure is growth.  Growth is an important fitness component of individual organisms, and may have an overall impact on the success of natural populations.  It is worth noting that although changes in a single fitness component may not always have a direct influence on the overall fitness of an individual, growth tends to integrate and reflect most sublethal effects. Google = about 799 Nov. 9, 2004; about 653 Oct. 11, 2005, about 11,000 Nov 14, 2006, about 2,270 Dec 9, 2008; about 6,230 Dec 7, 2009

PK/PD markers: Pharmacokinetic/pharmacodynamic markers

plasma biomarkers: SEE serum biomarkers Google = about 250 Aug. 18, 2003; about 775 Sept. 2, 2004; about 11,600 Oct. 11, 2005, about 26,600 Nov 14, 2006, about 18,300 Dec 9, 2008; about 56,000 Dec 7, 2009

preclinical safety biomarkers: The tests that are used to determine drug safety today have not changed in decades. Companies have developed newer safety testing methods, but these are not generally accepted by the FDA or EMA as proof of safety because the tests have not been independently validated by a third party.... to find improved testing methods, C-Path has invited pharmaceutical companies to join the PSTC in which they share their internally developed methods and then test the methods developed by another member of the Consortium. Ten EMA and nineteen FDA scientists participate as advisors, along with more than 250 participating scientists, with C-Path serving as the "trusted third party," leading the collaborative process, collecting and summarizing the data. Predictive Safety Testing Consortium PSTC, Critical Path Institute, 2008-2010 http://www.c-path.org/pstc.cfm 

predictive biomarkers:  It is within pivotal phase III clinical trials that predictive biomarkers have the greatest potential to affect clinical practice by targeting drugs under development to relevant patient subgroups. Predictive biomarkers can be integrated into phase III clinical trials by a variety of approaches, including trial designs that uncouple the processes and actively anticipate the emergence of new biomarkers during trial execution. Parallel paths to predictive biomarkers in oncology: Uncoupling of emergent biomarker development and phase III trial execution, Sikorski R, Yao B. Sci Transl Med. 2009 Dec 9;1(10):10ps11. http://www.ncbi.nlm.nih.gov/pubmed/20368158

A biomarker that is present prior to an event occurring and which predicts that outcome.  Google = about 571 Sept. 2, 2004; about 839 Oct. 11, 2005, about 22,200 Nov 14, 2006, about 20,200 Dec 9, 2008; about 77.500 Dec 7, 2009

Predictive Safety Testing Consortium PSTC:: Non-profit consortium led by C-Path the Critical Path Institute brings together pharmaceutical companies to share and validate each other's safety testing methods under advisement of the Food and Drug Administration ("FDA") and its European counterpart, the European Medicines Evaluation Agency ("EMEA"). The 15 corporate members of the consortium share internally developed pre-clinical safety biomarkers in five workgroups: carcinogenicity, kidney, liver, muscle and vascular injury. Predictive Safety Testing Consortium PSTC, Critical Path Institute  http://www.c-path.org/pstc.cfm 

primary biomarkers:  In order to search for the specific biomarkers of patients with influenza-associated encephalopathy this article analyzed all metabolites in cerebrospinal fluid (CSF) by using metabolome analysis. In all metabolites, the peaks of two molecular weights, 246.0092 and 204.0611, were significantly higher than those in other diseases including influenza without convulsion (p < .05). Kawashima H, Oguchi M, Ioi H, Amaha M, Yamanaka G, Kashiwagi Y, Takekuma K, Yamazaki Y, Hoshika A, Watanabe Y., Primary biomarkers  in cerebral spinal fluid obtained from patients with influenza-associated encephalopathy analyzed by metabolomics, Int J Neurosci 116(8): 927- 936, 2006 Aug   Google = about 65 Oct. 25, 2004, about 311 Oct. 11, 2005, about 177 Nov 14, 2006, about 410 Dec 9, 2008; about 994 Dec 7, 2009  Related term: secondary biomarkers

probable valid biomarker:  A biomarker that is measured in an analytical test system with well established performance characteristics, and for which there is a scientific framework or body of evidence that appears to elucidate the physiologic, toxicologic, pharmacologic, or clinical significance of the test results. A probable valid biomarker may not have reached the status of a known valid marker because, for example, of anyone of the following reasons: -- the data elucidating its significance may have been generated within a single company and may not be available for public scientific scrutiny., -- The data elucidating its significance, although highly suggest, may not be co conclusive. -- Independent verification of the results may not have occurred. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

prognostic biomarkers: provide information regarding outcome irrespective of therapy. ..Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen; estrogen receptor (ER) and progesterone receptor (PR) overexpression; markers of oncogene overexpression such as c-erbB-2, transforming growth factor-α (TGF-α), and EGFr; indicators of apoptotic imbalance, including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals, such as overexpression of c-myc and related proteins; loss of differentiation markers, such as TGF-β II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as vascular endothelial growth factor (VEGF) overexpression. Molecular Biomarkers for Breast Cancer Prognosis: Coexpression of c-erbB-2 and p53 Samuel W. Beenken et al, Annals of Surgery 2001 May; 233(5): 630–638. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421302/  See also under biological markers  Google = about 67,900 Dec 7, 2009

protein biomarkers: The challenge that the protein biomarker field is facing today is translation into clinical applications, partially due to the complexity of serum/plasma mixtures, the relative immaturity of proteomics technologies, and the high costs and low speeds of validation. Biomarkers can be protein or proteomic, but need not be. Google = about 386 Aug. 6, 2002; about 1,010 Aug. 18, 2003, about 3,750 Sept. 2, 2004, about 139,000 Nov 14, 2006, about 57,300 Dec 9, 2008; about 62,700 Dec 7, 2009  See also genomic biomarkers, metabolic biomarkers  Broader terms: biological markers, biomarkers   Related term: biosignatures

proteomic biomarkers: A protein expression pattern that is able to discriminate or predict. Google = about 26, Sept. 2, 2004; about 381 Oct. 11, 2005, about 820 Nov 14, 2006, about 7,850 Dec 9, 2008; about 30,500 Dec 7, 2009

qualitative biomarkers: those present in one patient group but not another, and are thus easily found. Clinical Proteomics: From Diagnosis to Therapy  By Jennifer E. Van Eyk, Michael J. Dunn, Wiley VCH, 2008 http://books.google.com/books?id=XZXO2TTq9K0C&printsec=frontcover#v=onepage&q=&f=false

quantitative biomarkers: present in different patient groups, in different degrees. ... whether single proteins or groups of proteins, require the use of statistical tests to assist in their discovery. Clinical Proteomics: From Diagnosis to Therapy  By Jennifer E. Van Eyk, Michael J. Dunn, Wiley VCH, 2008 http://books.google.com/books?id=XZXO2TTq9K0C&printsec=frontcover#v=onepage&q=&f=false

regulatory biomarker: A biomarker being used to support scientific arguments made by the sponsor about drug dosing, safety, patient selection, or effectiveness, or that the sponsor proposes to describe in the drug label; or that are essential to achieve the dosing, safety, or effectiveness described in the drug label, or that will be used for decision making in any clinical trial or in an animal trial used to support safety. Biomarkers in Clinical Development: Implications for Personalized Medicine and Streamlining R&D  Insight Pharma Report, 2005  Google = about 201 Dec 7, 2009

reporter biomarkers: A biomarker that is present as a result of an event occurring.  Google = about 4 Oct. 25, 2004; about 8 Oct. 11, 2005, about 6 Nov 14, 2006, about 4 Dec 9, 2008; about 7 Dec 7, 2009

response biomarkers: including measures of endogenous substances or parameters indicative of pathological or biochemical changes both toxicodynamic and pharmacodynamic, resulting from exposure to drugs and other chemicals. . Biomarkers, Informa, Aims & Scope http://informahealthcare.com/page/Description?journalCode=bmk  Google = about 10,400 Dec 7, 2009

response variability in biomarkers:  Biomarkers can be inappropriately applied or misinterpreted, because the fundamental assumptions in exposure– response relations have not been considered. Factors causing temporal and spatial variability in biomarker responses are reviewed. These include numerous geochemical and biotic variables. The variation can be minimised by appropriate study site selection, experimental replication, multivariate epidemiological approaches, normalised controls, and temporal calibration of responses; so that the regulatory use of biomarkers for biomonitoring and tracking pollution events, including chronic or multiple exposures to complex mixtures is possible. RD Handy et. al, A proposal for the use of biomarkers for the assessment of chronic pollution and in regulatory toxicology, Ecotoxicology, 12 (1-4): 331-343 Feb. 2003

risk biomarkers: Risk biomarkers [for breast cancer] are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering, and inherited germ-line abnormalities. Molecular Biomarkers for Breast Cancer Prognosis: Coexpression of c-erbB-2 and p53 Samuel W. Beenken et al, Annals of Surgery 2001 May; 233(5): 630–638. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421302/ 

Quantifiable, well-characterized cancer risk factors demonstrate the need for chemoprevention and define cohorts for chemopreventive intervention. For chemoprevention, the important cancer risk factors are those that can be measured quantitatively in the subject at risk. ... Generally, the risk biomarkers fit into categories based on those previously defined by Hulka: 1) carcinogen exposure, 2) carcinogen exposure/effect, 3) genetic predisposition, 4) intermediate biomarkers of cancer, and 5) previous cancers. Besides their use in characterizing cohorts for chemoprevention trials, some risk biomarkers can be modulated by chemopreventive agents. These biomarkers may be suitable surrogate endpoints for cancer incidence in chemoprevention intervention trials. Risk biomarkers and current strategies for cancer chemoprevention, Kelloff GJ et al , J Cell Biochem Suppl. 1996;25:1-14

RNA biomarkers: A huge number of human transcripts has been found that do not code for proteins, named non-protein coding RNAs. In most cases, small (miRNAs, snoRNAs) and long RNAs (antisense RNA, dsRNA, and long RNA species) have many roles, functioning as regulators of other mRNAs, at transcriptional and post-transcriptional level, and controlling protein ubiquitination and degradation. Various species of npcRNAs have been found differentially expressed in different types of cancer.  Massimo Mallardo , Palmiro Poltronieri, and Oscar Fernando D'Urso, Non-protein coding RNA biomarkers and differential expression in cancers: a review, Journal of Experimental & Clinical Cancer Research 2008, 27:19doi:10.1186/1756-9966-27-19 http://www.jeccr.com/content/27/1/19  Google = about 1,160 Dec 9, 2008; about 2,940 Dec 7, 2009

safety biomarkers: Application of any new biomarker to support safety-related decisions during regulated phases of drug development requires provision of a substantial data set that critically assesses analytical and biological performance of that biomarker. Such an approach enables stakeholders from industry and regulatory bodies to objectively evaluate whether superior standards of performance have been met and whether specific claims of fit-for-purpose use are supported. Towards consensus practices to qualify safety biomarkers for use in early drug development. Sistare FD et. al, Nat Biotechnol. 2010 May;28(5):446-54. Epub 2010 May 10. http://www.ncbi.nlm.nih.gov/pubmed/20458314 

Could be defined as the absence of any toxicity biomarkers. May not truly exist.  Google = about 194 Sept. 2, 2004; about 262 Oct. 11, 2005, about 605 Nov 14, 2006, about 4,650 Dec 9, 2008; about 441,000 Dec 7, 2009

secondary biomarkers: Secondary analytes are defined as analytes that, if present outside the reference range in addition to an out-of-range primary analyte, increase the risk that a specific disorder is present. A secondary analyte alone may not indicate a specific risk for the disorder in question. For simplicity, ratios of analytes are considered secondary biomarkers and are not listed. Naming and Counting Disorders (Conditions) Included in Newborn Screening Panels, Lawrence Sweetman, PhDa, David S. Millington, PhDb, Bradford L. Therrell, PhDc, W. Harry Hannon, PhDd, Bradley Popovich, PhDe, Michael S. Watson, PhDf, Marie Y. Mann, MD, MPHg, Michele A. Lloyd-Puryear, MD, PhDg and Peter C. van Dyck, MD, MPHg, PEDIATRICS Vol. 117 No. 5 May 2006, pp. S308-S314 (doi:10.1542/peds.2005-2633J) http://pediatrics.aappublications.org/cgi/content/full/117/5/S1/S308 Google = about 22, Oct. 25, 2004; about 68 Oct. 11, 2005, about 113 Nov. 14, 2006, about 254 Dec 9, 2008; about 854 Dec 7, 2009  Related terms: primary biomarkers, surrogate biomarkers, surrogate endpoints

selection biomarkers: Disease-associated analytes whose measurement is either an essential step in patient screening or the primary objective of a clinical trial. The public database ClinicalTrials.gov contains information on most active phase III oncology clinical trials that can be examined for trends in the development of cancer therapies. But for selection biomarkers, such information is not easily accessible and so has not been examined in a comprehensive way. Here we provide a global analysis of selection biomarkers currently in use in the oncology phase III trial arena. Visualizing the Landscape of Selection Biomarkers in Current Phase III Oncology Clinical Trials, .Sikorski R, Yao B. Sci Transl Med. 2010 Jun 2;2(34):34ps27. http://www.ncbi.nlm.nih.gov/pubmed/20519717

serum biomarkers: Physicians have used changes in serum biomarkers to judge response to therapy or to define the rate of disease progression. Many markers that are of limited value in screening for cancer are valuable for monitoring for recurrences. Distilling Cancer Biomarkers From the Serum Peptidome: High Technology Reading of Tea Leaves or an Insight to Clinical Systems Biology? Richard J. Robbins, Josep Villanueva, Paul Tempst, Journal of Clinical Oncology, 23(22): 4835- 4837, Aug. 1, 2005 http://www.jco.org/cgi/content/full/23/22/4835 Google = about 613 Aug. 18, 2003; about 701 Aug. 18, 2003; about 1,720 Sept. 2, 2004; about 19,100 Oct. 11, 2005, about 44,9000 Nov 14, 2006, about 39,000 Dec 9, 2008; about 137,000 Dec 7, 2009

small molecule biomarkers: Compared to protein biomarkers, small molecule biomarkers (or metabolic biomarkers) are less species dependent. Therefore, data from animal studies with small molecule biomarkers should be translatable to the human condition. Small Molecule Biomarkers, Drumetix Laboratories, 2010 http://www.drumetix.com/php/small-molecule-biomarkers.php 

SNP biomarkers: Genetic polymorphisms may constitute in-built determinants of individual differences in response to IFN-β. Prior attempts to identify such ‘predictors of response’ were hypothesis- driven in that they were based on preselection of candidate genes associated with Type I interferon pathways. In the present study, the authors performed the first ever nonbiased genome- wide association screen in an attempt to identify response-predictive SNPs.  Koen Vandenbroeck http://www.futuremedicine.com/entityImage/?code=200B1 http://www.futuremedicine.com/entityImage/script/2020.gif & Carlos Matute http://www.futuremedicine.com/entityImage/?code=200B2, Pharmacogenomics of the response to IFN-β in multiple sclerosis: ramifications from the first genome-wide screen, Pharmacogenomics, May 2008, Vol. 9, No. 5, Pages 639 - 645 (doi:10.2217/14622416.9.5.639) http://www.futuremedicine.com/doi/abs/10.2217/14622416.9.5.639  Google =- about 159 Dec 9, 2008; about 190 Dec 7, 2009 Related terms: SNPs single nucleotide polymorphisms glossary

staging biomarkers: Distinguishes between different stages of a chronic disorder. Google = about 6, Oct. 25, 2004; about 21 Oct. 11, 2005, about 27 Nov 14, 2006, about 110 Dec 9, 2008; about 398 Dec 7, 2009

standard operating procedures SOPs for biomarkers:  In all pharmaceutical companies, standard operating procedures (SOPs) for planning, implementing, and employing biomarkers remain a work in progress, continually evolving as still-scarce outcomes data from biomarker- driven programs becomes available. Biomarker SOPs: Getting Optimum Value from Your Biomarker Programs  Insight Pharma Report, 2007 

stratification biomarkers:  the use of biomarkers can help identifying patients that are more likely to respond favourably to a given therapy. Until now, biomarkers have been used in clinical practice to describe both normal and pathological conditions. Increasingly, they find application in order to stratify different patient groups in terms of clinical response, so as to develop personalised, preventive or therapeutic strategies.  Workshop "Stratification biomarkers in personalised medicine" European Commission Brussels June 10-11 2010 http://ec.europa.eu/research/health/pdf/biomarkers-for-patient-stratification_en.pdf 

surrogate biomarkers:  A “surrogate marker” can be defined as “a laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful endpoint that is a direct measure of how a patient feels, functions, or survives and is expected to predict the effect of the therapy.”5 The primary difference between a biomarker and a surrogate marker is that a biomarker is a “candidate” surrogate marker, whereas a surrogate marker is a test used, and taken, as a measure of the effects of a specific treatment. Russell Katz, Biomarkers and Surrogate Markers: An FDA Perspective, NeuroRx 1(2): 189-195, April 2004  http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=534924 

Biomarker that reflects an indirect consequence of an event or disorder. Alternatively, secondary biomarker  Google = about 671 Sept. 2, 2004, about 932 Oct. 11, 2005, about 15,800 Nov 14, 2006, about 8,380 Dec 9, 2008; about 18,700 Dec 7, 2009

surrogate endpoint biomarkers:  tissue, cellular, or molecular alterations that occur between cancer initiation and progression. These biomarkers are used as end points in short-term chemoprevention trials. Molecular Biomarkers for Breast Cancer Prognosis: Coexpression of c-erbB-2 and p53 Samuel W. Beenken et al, Annals of Surgery 2001 May; 233(5): 630–638. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421302/ 

surrogate endpoint marker:  The rare biomarker that can substitute (or be a surrogate) for a clinical end point, such as survival, stroke, fracture, or cancer recurrence.  Stephen M. Hewitt*, James Dear and Robert A. Star, Discovery of Protein Biomarkers for Renal Diseases, J Am Soc Nephrology 15:1677-1689, 2004  http://jasn.asnjournals.org/cgi/content/full/15/7/1677 

surrogate endpoints:  Outcome measures that are not of direct practical importance but are believed to reflect outcomes that are important; for example, blood pressure is not directly important to patients but it is often used as an outcome in clinical trials because it is a risk factor for stroke and heart attacks. Surrogate endpoints are often physiological or biochemical markers that can be relatively quickly and easily measured, and that are taken as being predictive of important clinical outcomes. They are often used when observation of clinical outcomes requires long follow-up. Also called: Intermediary outcomes, Surrogate outcomes Cochran Collaborative Glossary  2010. http://www.cochrane.org/glossary/5 

A biomarker intended to substitute for a clinical endpoint.  A surrogate endpoint is expected to predict clinical benefit (or harm, or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiology or other scientific evidence. Biomarkers Definition Working Group, 1998, Gregory Downing, NIH Initiatives in Surrogate Endpoints and Endpoint Analysis,  Nonclinical Studies Subcommittee, Advisory Committee for Pharmaceutical Science presentation, 2000 http://www.fda.gov/ohrms/dockets/ac/00/slides/3593S1_03_downing.ppt 
Google = about 2,570 Aug. 6, 2002; about 10,200 Aug. 18, 2003; about 9,200 Sept. 2, 2004; about 72,600 Oct. 11, 2005, about 128, 000 Nov 14, 2006, about 53,700 Dec 9, 2008; about 59,000 Dec 7, 2009
Related terms: biomarkers, surrogate markers.   
Wikipedia: http://en.wikipedia.org/wiki/Surrogate_endpoint 

surrogate markers:  A laboratory or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful endpoint that is a direct measure of how a patient feels, functions, or survives and that is expected to predict the effect of the therapy  (Temple, 1999) Surrogate Markers and its role in the  Drug Development Process, Aloka G. Chakravarty, 2004? American Statistical Association http://docs.google.com/viewer?a=v&q=ca...eU2TchGxExHQUeXwOtGX9ccU0jcAnlZ97uO1MU1kT-SQjYmHCYmUM1&sig=AHIEtbQqYjysay188TqCxHSj-RJXuFVSPg Google = about 5,920 Aug. 6, 2002; about 22,300 Sept. 2, 2004; about 185,000 Oct. 11, 2005, about 370,000 Nov 14, 2006, about 162,000 Dec 9, 2008; about 161,000 Dec 7, 2009  Related terms: biomarkers, surrogate endpoints

susceptibility biomarkers:: Include genetic factors which alter susceptibility to drugs and other chemicals. Biomarkers, Taylor & Francis, Aims & Scope http://www.tandf.co.uk/journals/titles/1354750x.asp  Google = about 1,780 Dec 9, 2008; about 6,200 Dec 7, 2009

target biomarkers: A biomarker that reflects the presence of a specific molecular drug target.  Google = about 44 Sept. 2, 2004; about 154 Oct. 11, 2005, about 273 Nov 14, 2006, about 1,030 Dec 9, 2008; about 2,930 Dec 7 2009  Related term: gene target: Drug Targets

therapeutic markers: become evident as the treatment of a chronic disease progresses in the patient. These markers are influenced by many factors, including individual nature of the disease, drug treatment, patient activities, etc. Proteomics-based Development of Biomarkers in Cardiovascular Disease Mechanistic, Clinical, and Therapeutic Insights Manuel Mayr et al., Molecular & Cellular Proteomics 5:1853-1864, 2006. http://www.mcponline.org/cgi/content/full/5/10/1853?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=3570&resourcetype=HWFIG

translational biomarkersThe pharmaceutical industry must find ways to improve the unacceptably high attrition rate during drug development. Clearly, pharma has moved away from treat-and-see testing of new drugs in patients, with a strong current focus on generating translational biomarkers early in the research process to enable more predictive evaluation of drug action in clinical trials. Underlying such a translational medicine approach is the intensive search for and use of high-quality biomarkers indicative of successful drug target engagement, pharmacological effects, efficacy or safety. From biomarker strategies to biomarker activities and back, van Gool AJ, Henry B, Sprengers ED.,  Drug Discov Today. 2010 Feb;15(3-4):121-6. Epub 2009 Nov 18. http://www.ncbi.nlm.nih.gov/pubmed/19931413

tumor markers: Cancer genomics & diagnostics  Google = about 19,000 Aug. 6, 2002; about 27,700 Aug. 18, 2003; about 66,500 Sept 2, 2004   "tumour markers" about 16,300 Sept. 2, 2004, about 669,0000 Dec 9, 2008; about 463,000 Dec 7, 2009  Related term: biological tumor markers

type 0 biomarkers: Markers of the natural history of a disease and correlate longitudinally with known clinical indices, such as symptoms over the full range of disease states.... Type 0 markers can be characterized in phase 0 clinical studies, in which a reliable assay is used in a well defined patient population for a specified period of time. Ideally, a linear (positive or negative) relationship is established with the 'gold standard' clinical assessor.  Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003  Google = about 90 Dec 7, 2009  Related term: Drug approvals ^ clinical trials phase zero 

type I biomarkers: Capture the effects of an intervention in accordance with the mechanism of action of a drug , even though the mechanism may not be associated with clinical outcome. ...A priori validation of Type I biomarkers is impossible for truly novel targets without an effective positive control treatment. By definition, the more innovative the target, the less validated will be the associated biomarkers.  Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003  Google = about 545 Dec 7, 2009

type II biomarkers: Are considered surrogate endpoints because a change in that marker predicts clinical benefit. ... Type II biomarkers (or surrogate end-points) must be relevant both to the mechanism of action of the drug and to the pathophysiology of the disease. Changes in the biomarker should reflect treatment benefit and therefore effective therapy is necessary for this validation. Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003  Google = about 17,200 Dec 7, 2009

valid biomarker: A  biomarker that is measured in an analytical test system with well-established performance characteristics and for which there is an established scientific framework or body of evidence that elucidates the physiologic, toxicologic, pharmacologic, or clinical significance of test results. The classification of biomarkers is context specific. Likewise, validation of a biomarker is context-specific and the criteria for validation will vary with the intended use of the biomarker.  The clinical utility (e.g. predict toxicity, effectiveness or dosing) and use of epidemiology/ population data (e.g. strength of genotype- phenotype associations) are examples of approaches that can be used to determine the specific context the necessary criteria for validation.  Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf   Google = about 6,200 Dec 7, 2009  Narrower terms: known valid biomarker, probable valid biomarker  See also genomic biomarkers

validation - biomarkers:  Cancer genomics Cancer biomarker validation distinguishes between analytical validation and clinical validation. 

Bibliography
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Richard Frank, Richard Hargreaves, Clinical biomarkers in drug discovery and development. Nature Reviews Drug Discovery. 2(7): 566- 580, July 2003
FDA, E15 definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories April 2008  http://www.fda.gov/RegulatoryInformation/Guidances/ucm129286.htm 
FDA Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126957.pdf 
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Diagnostics Conferences http://www.healthtech.com/Conferences/Search.aspx?k=&r=&s=BMK
Accelerating Development & Advancing Personalized Therapy ADAPT http://www.adaptcongress.com/
Biomarker World Congress http://www.biomarkerworldcongress.com/
Molecular Medicine Tri Conference http://www.triconference.com/
Next Generation Diagnostics http://www.nextgenerationdx.com/
Next Generation Sequencing NGX http://www.chicorporate.com/sqe?c=6911

Diagnostics CDs, DVDs  http://www.chicorporate.com/Conferences/CompactDiscs.aspx?s=BMK
Diagnostics Short courses http://www.healthtech.com/Conferences_Upcoming_ShortCourses.aspx?s=BMK

Insight Pharma Reports Biomarkers & Diagnostics Series http://www.insightpharmareports.com/Reports/All.aspx?s=BMK 

Alpha glossary index
How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

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