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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 ADAPT September 19-21, 2012 • Washington, DC Program | Register | Download Brochure 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
Biological
markers can reflect a variety of disease characteristics, including the level of
exposure to an environmental or genetic trigger, an element of the disease
process itself, an intermediate stage between exposure and disease onset, or an
independent factor associated with the disease state but not causative of
pathogenesis. Depending on the specific characteristic, biomarkers can be used
to identify the risk of developing an illness (antecedent biomarkers),
aid in identifying disease (diagnostic biomarkers), or predict future
disease course, including response to therapy (prognostic biomarkers).
Antecedent Biomarkers in Alzheimer's Disease, Alzheimers Research Forum,
2003 http://www.alzforum.org/res/enab/workshops/biomarkers.asp 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
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:
Features translational tools: mass
spectrometry, NMR, antibody DNA & RNA arrays, spectroscopy & imaging,
flow cytometry, cell based assays, biochemical & immunoassays . Biomarker Assay
Development Jan. 31- Feb 2, 2011, San Diego CA Program
| Register
| Download Brochure biomarker
discovery informatics: from early stage
pharmaceutical research organizations, to late stage clinical trials
organizations and clinical settings – in an effort to address the informatics
and organizational challenges inherent in the development of personalized and
clinically relevant biomarkers ... cutting edge efforts and successes in the
discovery of personalized biomarkers for drug development and diagnosis driven
by genetics, systems biology and integrated informatics approaches. Biomarker
Discovery Informatics September 8-9, 2011 • Philadelphia, PA Program
| | Download Brochure
biomarker qualification process:
The European Medicines Agency (EMEA) and the US
Food and Drug Administration (FDA) have concluded the first joint qualification
process for biomarkers, following the submission of scientific data by the
Predictive Toxicology Consortium (C-Path PSTC).
Under the C-Path PSTC, the pharmaceutical industry has for the first time pooled
together data from different companies in order to achieve the critical mass of
scientific information that allowed the EMEA and FDA to qualify the use of seven
biomarkers of drug-induced renal toxicity in the context of non-clinical drug
development. Data were submitted to both regulatory agencies and jointly
evaluated using state-of-the-art standards. Biomarkers, Medicines &
Emerging Science, EMEA European Union http://www.emea.europa.eu/htms/human/mes/biomarkers.htm
Biomarker
SOPs: Getting Optimum value from your biomarker program
Drug
discovery & development, clinical response, mechanisms of action, efficacy,
& safety biomarkers, Insight Pharma Reports, 2007
Biomarker
World Congress
May 21-23, 2012 •
Philadelphia, PA Program | Register | Download
Brochure 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.1–4
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/ 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.
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
cancer
molecular markers: Covers
solid tumors: Lessons for biomarker validation, microRNA signature for
diagnostics and prognostics, novel technologies for isolation, detection and
characterization of circulating tumor cells, clinical Circulating Tumor Cells,
growth in personalized cancer diagnostics,
hot pathways in cancer stem cells ultra malignant cells
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: Executive Summit:
Clinical Biomarkers September
19-21, 2012 • Washington, DC Program | Register | Download Brochure This report focuses on
disease-related biomarkers, those related to disease screening, prognosis, and
stratification — more specifically, disease-related molecular biomarkers.
Insight Pharma, Disease Related Biomarkers: Their Potential in Patient
Screening, Prognosis and Stratification, 2007 http://www.insightpharmareports.com/reports/2007/83_Disease_Biomarkers/overview.asp
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: The journal publishes original research
findings (and reviews solicited by the Editor) on the subject of the
identification of markers associated with the disease processes whether or not
they are an integral part of the pathological lesion. The disease markers may be
a genetic host factor predisposing to the disease or the occurrence of
cell-surface markers, enzymes or other components, either in altered forms,
abnormal concentrations or with abnormal tissue distribution. Disease
Markers, Aims and Scope, IOS Press http://www.iospress.nl/html/02780240.php
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 drug development and
biomarkers: Biomarkers as decision making tools, implementing personalized
medicine, technologies, translational biomarkers, toxicity biomarkers, biomarker
qualification and development, predictive and prognostic biomarkers and patient
selection Biomarkers
in Drug Development
May 2-4, 2011 • Philadelphia, PA Program
| Register
| Download Brochure 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
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
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/RegulatoryInformation/Guidances/ucm129296.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. 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 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 miRNA
biomarkers: 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 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 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 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 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). 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/
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
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
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
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 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 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
biomarkers:
With new initiatives from regulators to have biomarker assays
available as drugs are developed, the role of biomarkers has shifted. The latest
in translatable biomarkers (pharmacodynamic, predictive, prognostic,
toxicological and diagnostic) will be showcased. Animal models have been
used for decades in pharmaceutical research, but with limited success for direct
prediction in man. Experts will identify both models and strategies for using
biomarkers that will create correlations, predictivity and translation to the
clinic. Pharmacodynamic biomarkers, utilized in pre-clinical and early
clinical development, demonstrate effective targeting while predictive
biomarkers (in late clinical development) can indicate the efficacy of
treatment. Translational
Biomarkers September 8-9, 2011 • Philadelphia, PA Program
| | Download Brochure 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 Diagnostics Conferences http://www.healthtech.com/Conferences/Search.aspx?k=&r=&s=BMK Alpha
glossary index IUPAC definitions are reprinted with the permission of
the International Union of Pure and Applied Chemistry.
Evolving Terminologies for Emerging Technologies
Comments? Questions?
Revisions? Mary Chitty mchitty@healthtech.com
Last revised June 15, 2012
<%end if%>
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/
Biomarker World Congress May 21-23,
2012 • Philadelphia, PA Program | Register | Download Brochure
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
Related/synonymous? terms: biomarkers, genetic markers, protein biomarkers, surrogate markers;
Broader term: markers
Narrower term: genomic biomarkers
Biomarker
Assay Development January 31 - February 1, 2012 • San Diego, CA Program | Register
| Download Brochure The
increasing importance of biomarkers in drug discovery and development of
diagnostics calls for a comprehensive biomarker strategy that must include assay
development and validation.
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
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
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
See also Cancer
genomics & diagnostics
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
Biomarkers offer
actionable data for efficacy, MOA, safety, and pharmacology evaluation, leading
to more informed lead selection. 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
Wikipedia:
genetic marker
http://en.wikipedia.org/wiki/Genetic_marker
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
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
Wikipedia:
molecular marker http://en.wikipedia.org/wiki/Molecular_marker
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
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
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
1
& Carlos Matute
2, 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)
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
Translational Biomarkers DVD August 19, 2010 •
The 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
Biomarkers and surrogate
endpoints: Preferred definitions and conceptual framework, Clinical Pharmacology
and Therapeutics 69: 89- 95, 2001
Considerations in the evaluation
of surrogate endpoints in clinical trials: Summary of a National Institutes of
Health workshop, Controlled Clinical Trials 22¨485-502, 2001
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
IUPAC International Union of Pure and Applied Chemistry, GLOSSARY FOR CHEMISTS
OF TERMS USED IN TOXICOLOGY Clinical Chemistry Division, Commission on
Toxicology, Pure and Appl. Chem., 65 ( 9): 2003- 2122, 1993. 1200+
definitions. http://www.iupac.org/reports/1993/6509duffus/
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
Insight Pharma Reports
Approaches
to reducing Clinical Trials Phase II Attrition and improving drug development
productivity: 2009
Insight Pharma Reports Biomarkers, Proof of Concept, Microdosing, Adaptive
Clinical Trials & Translational medicine 2009 http://insightpharmareports.com/uploadedFiles/Reports/Complimentary_Content/AnimalModels.pdf
Insight Pharma Reports, Biomarker
SOPs: Getting Optimum value from your biomarker program Drug
discovery & development and clinical response biomarkers, mechanism of
action biomarkers, efficacy biomarkers and safety biomarkers 2007
Insight Pharma Reports, Cancer
Biomarkers: Adoption is Driving Growth, 2008
Insight Pharma, Disease Related Biomarkers: Their Potential in Patient
Screening, Prognosis and Stratification, 2007
How
to look for other unfamiliar terms
