Index

Abatacept, 612, 615, 617 Absolute risk, 266

Absorption, distribution, metabolism and elimination (ADME), 34, 504, 543, 594,610

Accelerated Approval Rule, 490 Acceptance criteria, 189, 198, 202-204, 206208, 252, 255,275 Accreditation, 84, 464-465, 626 Acquired immune deficiency syndrome

(AIDS), 17, 414, 554, 700 ACR20, 612-613, 616-617 Actemra, 129

Activated partial thromboplastin time

(aPTT), 415, 447-449, 456-457, 459 Acute coronary syndrome (ACS), 129, 544 Acute interstitial nephritis, 338 Acute phase reactants, 121, 128 Adaptive design, 240, 364, 372 Adipokines, 115

Adverse event(s), 80, 228-229, 233, 240, 290, 315, 331-332, 363, 369, 434, 439, 441, 508, 556, 582-583, 701 Adverse reaction(s) (AR), 179, 226-229, 435, 629

Adverse responses, 291, 294, 435 Alanine aminotransferase (ALT), 291, 440 Aldosterone, 371, 415

Algorithm(s), 83, 105, 130, 137-138, 143, 146, 149, 180, 203, 278, 280, 283, 316, 365, 389, 392, 507, 559, 598, 603, 654, 667, 689

Allele frequency(s), 611, 616

628, 696, 704 Alzheimer's Disease Neuroimaging Initiative

(ADNI), 86 American Association for Cancer Research, 23

American Association of Bioanalysts (AAB), 465

American Association of Blood Banks

(AABB), 465 American Board for Clinical Chemistry, 469

American Board of Bioanalysts, 469 American Board of Medical Genetics, 469 American Board of Medical Microbiology, 469

American Board of Pathology, 469 American College of Radiology (ACR), 84 American Society for Clinical Oncology, 23, 150

American Society for Histocompatibility and

Immunogenetics (ASHI), 465 Aminoglycoside(s), 295, 336, 338, 342 Amyotrophic lateral sclerosis, 24 Anaemia, see Anemia Anakinra, 129, 612, 614 Analysis Data Model (AdaM), 580 Analysis of variance (ANOVA), 268, 270272,282,650-651,666-667, 670 Anaphylaxis, 330 Anemia, 10, 328, 330, 336

Biomarkers in Drug Development: A Handbook of Practice, Application, and Strategy, Edited by Michael R. Bleavins, Claudio Carini, Malle Jurima-Romet, and Ramin Rahbari Copyright © 2010 John Wiley & Sons, Inc.

Angiogenesis, 67-70, 77, 114-115, 504, 605, 714

Angiography, 129, 701 Angiotensin, 337, 371, 415 Angiotensinogen, 115 ANOVA, 268, 270-272, 282, 650-651, 666667, 670. See also Analysis of variance Antibodies to citrullinated protein antigens

(ACPA), 405-406, 411 Antibody array(s), 124, 522 Anticoagulant, 192, 445, 447-448, 450-451,

454, 457, 459, 460 Antisera, 323, 330, 341, 343 Apolipoprotein, 128, 130, 341 Apoptosis, 67-68, 341, 439-440, 479, 504, 597 Armune BioScience, 523-525 Arrhythmias, 10, 371 Arthritis, 129, 400, 405-407, 415, 544, 634, 701, 704

Artifact, 76-77, 79, 102-103, 256, 454 Asthma, 127, 415, 697 Atorvastatin, 556. See also Statins Attrition, 188, 376-377, 438, 445-446, 460,

518, 548, 677, 694-695 AUC, 107, 111-112, 306, 311-312, 317, 417, 542

Auscultation, 6

Autoantibody(s), 168, 171, 324-325, 401,

404-405, 408-409, 516, 524-525 Autoantigen(s), 161, 172, 323, 615 Autoimmune , 128-129, 133, 155, 157,

402-403, 486,615, 617,721 Autoimmunity 331 Autoradiography, 136

Bayesian approach, 256, 281-282, 364, 658 Bayesian information, 280 Bayesian method, 277, 281 Bayesian modeling, 281, 283 Bayesian simulation, 255 Bayesian statistics, 240, 280 BCR-ABL, 17, 239, 368-369, 553, 598 Below the levels of quantitation (BLQ), 274-275

Benefit/risk, 594, 699. See also Risk/cost benefit and Risk-benefit Bilirubin, 292

Bioanalytical drug assay guidance, 208 Bioanalytical laboratory, 193, 196, 198, 200,

204, 207-208, 210 Bioanalytical method, 189, 207, 416 Bioanalytical validation, 207-208, 293, 380 Bioassay(s), 11, 252, 329, 459, 542

Bioavailability, 302-303, 693-695 Biobank, 395, 625-627, 629-637 Biodistribution, 68-69, 723 Bioinformatics, 21, 26, 86-87, 105-106, 110,

232,363,388-389 Bioinformatics Organization, 86 Biomarker Consortium, 86, 210 Biomarker Qualification Pilot Process, 182, 380

Biomarkers Definitions Working Group, 695

Biomarkers Technical Committee, 296

Biospecimens, 25

Bisphosphonates, 311, 427

Blanket consent, 633

Blocking patent(s), 659, 571

407, 416, 436, 665, 696-697,700 Blood urea nitrogen (BUN), 23, 181, 315, 335,

338, 344, 346, 350, 542 Bone marrow, 138, 438-439, 478, 617, 722 Bone mineral density (BMD), 426, 701-704 Brain, 9, 46-47, 76, 81, 193, 341, 343, 425,

Buprenorphine, 423-424

C-reactive protein, 130 Caco-2, 36 Calcitonin, 308, 310

Calcium, 301-316, 318-319, 336, 347, 546, 715 Calibration, 67, 80, 124, 218, 393, 450, 467 Canadian Citizen's Conference on

Biotechnology, 636 Canadian Public Consultation on Xenotransplantation, 636 Canadian Tumor Repository Network, 632 Cancer antigen 125 (CA-125), 63, 130 Cancer Biomedical Informatics Grid (caBIG), 87

Cancer Genome Atlas, 21

603, 606-607 Cardiology, 8, 55, 578 Cardiotoxicity, 144, 296 Cardiovascular disease, 18, 26, 127, 129, 187,

400, 405, 407-410, 478, 706 Cardiovascular effects, 304 Cardiovascular function, 303 Cardiovascular morbidity/mortality, 407-408 Cardiovascular parameters, 436 Cardiovascular risk, 555-556

Cardiovascular Research Grid (cvrGRID), 87

Cartilage oligomeric matrix protein (COMP), 410

Case report forms (CRFs), 582

C-C chemokine ligand 18 (CCL 18), 479-480

CCR5, 428-429, 554

Cecum, 305

Center for Biomarkers in Imaging, 46 Center for Devices and Radiological Health (CDRH), 231, 233, 235, 242-244

Center(s) for Disease Control, 555 Center for Drug Evaluation and Research (CDER), 179, 188, 229, 233, 240, 242-244

Centers for Medicare and Medicaid Services

(CMS), 85, 464-465 Central nervous system, 23, 127, 193, 303, 366,

370, 440, 479, 506, 545 Cetuximab, 239, 489 Chain of custody, 103, 197 Chemiluminescence, 124-125, 351 Chemokine(s), 121, 123, 127, 132, 415, 479, 554

Chemotherapy, 135-138, 141-142, 144-148,

150, 489,705 Chitotriosidase, 479-480 Chlorosis, 10

Cholesterol, 37, 85, 143, 270, 292, 336, 366, 368, 408, 415, 478, 555-556, 657, 696697, 700, 721 Chromatography, 12-14, 102, 104, 162, 190, 194,349,476 column, 555

high performance liquid (HPLC), 12 Chronic myelogenous/myeloid leukemia

(CML), 17, 366, 368, 553, 598 Chronic obstructive pulmonary disease

(COPD), 127, 415 Citrullinated antigens, 405 Citrullinated proteins, 404-406 Civic virtue, 637 Clinical acceptance, 238 Clinical Data Interchange Standards

Consortium (CDISC), 579, 581-583, 585-587

Clinical data management system (CDMS), 582

Clinical diagnostic surrogate biomarker, 52-53

Clinical Document Architecture (CDA), 580

Clinical Laboratory Improvement Act

Clinical Laboratory Improvement

Amendments (CLIA) of 1988, 473 Clinical Laboratory Standards Institute

(CLSI), 199-200, 208, 234 Clinical pathology, 290-292, 308, 446, 551, 555 Clinical registries, 18

Clinical relevance, 57, 149, 220, 255, 259, 479,

504, 508, 698 Clinical significance, 210, 250, 378, 500, 506 Clinical utility, 25-26, 225-228, 241, 335, 464 Clusterin, 23, 116, 181, 339, 341-342, 350 Cmax, 417, 542, 544-545 Code of Federal Regulations (CFR), 208,

232-235, 242, 244, 490, 588 Co-development, 17, 26, 179, 229, 231-232, 234, 236-244, 499, 508, 518, 529, 596 Coefficient of variation (CV), 102, 218-219,

262,650 Cognitive virtue, 637 Coincidence, 258

Collaborative Research and Development

Agreement (CRADA), 580, 586 Collagen type II neoepitope (TIINE), 558 College of American Pathology/College of

American Pathologists (CAP), 465, 522 Column chromatography, 555. See also

Chromatography Commercialization, 58, 85, 125, 132, 188, 517, 522-523,528-530,532-533,535,538539, 571, 583, 627,630 Common Procedural Terminology (CPT), 472 Companion diagnostics, 133, 216, 227-230, 232

Compendia Bioscience, 522, 525 Complement, 20-21, 68, 70, 105, 116, 131-132, 165, 219, 233, 295, 331, 341, 344, 366, 497-499, 654 Complement associated protein SP-40, 341 Complement cytolysis inhibitor protein, 341 Composition of matter, 569 Computational biology, 19, 627, 629 Computer model, 599 Confidence limit, 205, 217, 251 Confidentiality, 296, 627-628 Consortium, 20, 22, 85-86, 181-183, 210, 296,

338, 393, 631-632 Contract research organization(s) (CRO), 15,

67, 73, 267, 496, 583 Cooperate Research and Development Agreement (CRADA), 580, 586

Coronary artery disease, 55-56, 129, 700 Cost-benefit analysis, 226 Coumadin, 447-448, 450-451, 454, 457, 459 Council of Europe Committee of Ministers, 631

Council on Laboratory Accreditation

(COLA), 465 Creatinine, 23, 181, 193, 270, 291, 293, 306,

310, 315, 335, 337, 542, 546, 700 Creatinine kinase (CK), 293 Critical path initiative 231, 244, 416, 421 Critical Path Institute, 23, 181, 296, 338. See also Critical Path Initiative Critical Path Initiative (C-Path), 22-23, 85,

340, 343, 347, 491, 577. See also Critical Path Institute Crohn disease, 12, 7, 129, 701 Cross reactivity, 200, 234, 340, 351 Cross-validation, 138, 140, 143, 145-146, 209,

280, 384, 387 C-telopepetide of collagen type II (CTX II), 410

C-terminal hemagglutinin (HA) tag, 167 Cyclic citrullinated peptides (CCP), 405, 407,

409-410 Cyclophosphamide, 146 Cystatin C (Cys-C), 23, 181, 339, 342-343, 542 Cysteine protease inhibitor(s), 342 Cytokine(s), 115, 121, 123, 125, 127-130, 188, 196, 402, 404, 410, 415, 479, 486, 488, 517,544,612-614 Cytokine storm, 131 Cytotoxicity, 438, 440-441, 712, 715, 722

Data Discovery Query Builder (DDQB), 583 Data management, 18, 501, 582, 587 mining, 126, 207, 255, 559 warehouse(s), 587, 590 dbSNP, 582, 587

Decision gates, 33, 35-36, 498-499, 578-579 Decision theory, 664, 689 Declaration of Helsinki, 632 Declaration on Ethical Considerations

Regarding Health Databases, 631 DeCODE Genetics, 625, 630 Design around, 570-571 Detection limits, 217, 720 Development plan, 33, 35, 241, 243, 503 Diabetic nephropathy, 21 Diagnostic likelihood ratios (DLR), 219, 221-222 Diethylene glycol, 289

Differential diagnosis, 481, 660 Diffusion MRI, 76. See also Imaging Digital Imaging and Communications in

Medicine DICOM), 580-581, 585-586, 588

Disease modifying anti-rheumatic drugs (DMARD), 410, 612-613, 616-617 DNA hybridization, 721 Documentation, 103, 188, 194, 196-197, 202,

208-209, 235, 450, 588 Dose selection, 188-189, 303, 306, 381, 450,

458, 510 Dose-response, 74, 272, 318, 427 Doxorubicin, 146-148 Drug concentration(s), 201, 413-414, 417-420,

426, 449-450, 453, 455-459, 542 induced toxicity, 335, 435 safety, 188, 208. 239-240, 319, 429, 543, 547 target interactions, 57, 602 Drug-Diagnostic Co-Development, 179, 241 Duodenum, 305 Duration of action, 362 Dynamic Contrast Enhanced-MRI (DCE-MRI), 68-69, 70-80, 82-84. See also Imaging Dynamic range, 102, 104, 107

Echoencephalogram, 8 EIA, 329

Electrocardiogram (ECG), 10, 55, 436, 583 Electrocardiographic features, 10 Electrocardiographic QT interval, 543 Electrocardiography, 9, 543 Electrochemiluminescence, 124 Electroencephalograph (EEG), 10, 55, 446,

542-543 Electromagnets, 10

ELISA(s), 12, 108, 114, 123-124, 157, 164, 168, 171, 335, 339, 344, 349-351, 425, 554, 558 Endoscopy, 127, 701 Endothelial activation, 478 Endothelial cell(s), 347, 369, 597 Endothelial growth factor reception expression, 47 Endothelial marker(s), 478 Endothelial smooth muscle injury, 292 Endothelin, 130

Enrichment, 60, 103-104, 179, 238, 618 Entropy, 644, 647-648, 654-655

Epidermal growth factor, 130, 331, 415 Epidermal growth factor receptor (EGFR), 239, 301, 332, 489,507,547,584,586, ' 603, 605-607 Epigenetics, 187 Epigenomics, 19, 21

Epithelial cells, 139, 336, 339, 341-342, 345,

347-350, 440, 546 Epitope, 167, 324-325, 328, 332, 350, 403, 516,

524, 615, 714 Equilibrium, 275, 419, 426, 429, 644-649, 652,

689 ErbB, 713

ErbB2, 139, 250, 596 Erlotinib, 489, 507, 603-604, 607 Etiology, 292, 295, 336-337, 400, 402-403,

411,440,597, 608-609 European Medicines Association (EMEA),

23, 180-183, 296, 700 European Organization for Research and

Treatment of Cancer (EORTC), 62, 66 European Society for Human Genetics, 633 Exclusion criteria, 554 Exemption, 235, 243, 570-571 Extracellular signal-regulated kinases (ERK), 301-302

Extract-transform-load (ETL), 582, 586-587 Extrapolation, 157, 272, 421, 457 Eyeball test, 269

Factor X, 447-448, 450, 457-458, 535 Factor Xa (FXa), 447, 449-450, 452-458, 554-555

Family-wise error-rate control (FWER), 279 FatiGO, 389

Federal Food, Drug and Cosmetic Act, 232, 290

Femoral growth plate, 305 Femoral metaphysis, 305 Fibrinogen, 128, 188, 369, 405, 447 Fibrosis, 73, 115, 128, 236, 337, 339, 467, 471, 717

Fingerprinting, 106, 364, 607 First-in-human/first-in-man, 372, 459, 489, 510 Fit for purpose (FFP), 187, 189, 209, 211, 293,

349, 379, 381-383, 559 Flow cytometry, 11, 125, 438, 441 Fluorescence activated cell sorter (FACS), 11, 544

Fluorescence resonance energy transfer

(FRET), 711 Fluorescent in situ hybridization (FISH), 239, 557, 603

Fluorophore(s), 710, 715, 722 Fluoroscope, 7 Forensic biostatistics, 248 Forward pharmacology, 362 Foundation for the National Institutes of

Health (FNIH), 85-86, 88, 210 Fourier transform, 9 Fractionation, 104, 218 Fragmentation, 106 Freedom-to-operate (FTO), 570 Frog test, 11

Functional assay(s), 131, 196, 449

Gadolinium, 73-74, 79, 714 Galectin(s), 115-116 Galvanometer, 9

Gastrointestinal stromal tumors (GIST), 63, 66

Gastrointestinal tract, 303, 312-315 Gel electrophoresis, 14, 101, 122, 341, 472 GenBank, 582, 587 Gene amplification, 557, 603 frequency, 616

profiling, 135-139, 142, 144-151 Genetic Information Non-discrimination Act, 22

Genetic testing, 22, 26, 234, 466-467, 469-472,

586-587, 628, 633, 636 Genome mapping, 19

Genome wide association studies (GWAS),

19-21, 25, 225,403,490 Genomics Association Information Network

(GAIN), 21 Genotype, 21, 275, 277, 403, 477, 507, 577, 586, 599, 609-611, 614, 616-617, 643, 696 Genotyping blind, 276 error, 276-277 for enzymes, 507 of tumors, 364 process, 276, 480, 719 service(s) 589 technology, 608 Gentamicin, 342, 347

Gleevac/Gleevec, 17, 239, 369, 553. See also

Imatinib Globotriaosylceramide (Gb3), 477 Glomerular filtration rate (GFR), 335, 342 Glomerulosclerosis. 342, Glomerulus, 340, 342, 346 Glucagon, 188, 415, 609

Glucose, 48, 65, 82, 187, 233, 344, 415, 434, 437, 489, 545, 605, 607, 609, 611, 665, 704, 715, 720-721 Glucose transporter(s), 65 Glucosidase, 477

Glutathione S-transferase(s) (GSTs), 339-340,

343-344,350-351, 542 Glycolipid(s), 477

Glycoprotein, 341, 346-348, 350, 369 Glycoprotein III (GPIII), 341 Go/no go, 31-33, 35-36, 38, 507, 511 Goblet cell(s), 305

516, 555, 610 Good laboratory practice(s) (GLP), 127-128, 150, 188, 197, 202, 208, 414, 446, 504, 509-510 Governance virtue, 637 Granulocyte(s), 131, 132 Granulocyte colony stimulating factor

(G-CSF), 323 Growth factor(s), 121, 125, 188, 323 Guidance for Industry: Bioanalytical Method

Validation, 380 Guideline on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals, 290

Haemagglutination, see Hemagglutination Haematology, see Hematology Half-life, 34, 80-81, 326, 330, 417, 653 Haplotype, 20, 364, 614-615 HapMap, 20 Haptoglobin, 128, 130

629,631-632 HAVcr, 345

Hazard ratio (HR), 237 hCG, 11

Health and Environmental Sciences Institute, 338

343, 370-371, 415, 436,700,705 Heat map, 168, 605 Hemagglutination, 11-12 Hemangiosarcoma, 545 Hematology, 10-11, 306, 434, 438, 465 Hematopoiesis, 114 Hematopoietic cell line, 438 Hematopoietic toxicity, 438 Heparin, 336, 447-449, 456-457, 459, 478, 509

Heparin cofactor II-thrombin (HCII-T), 478

Hepatic cell(s), 440 Hepatic enzyme level(s), 142 Hepatic failure, 439 Hepatic microsome(s), 439 Hepatic protein(s), 439 Hepatic transformation system(s), 18 Hepatitis, 130, 330, 345 Hepatocellular necrosis, 305, 317, 542 Hepatocyte(s). 36, 343, 439-440 Hepatocyte screening, 36 Hepatotoxicity, 142-144, 295, 439-440 Her2/Her2/neu or Her2Neu, 17, 38, 489, 507,

556-557, 713 HER2 receptor protein, 68, 507 Herceptin, 17, 38, 227, 239, 370, 507, 556. See also Trastuzumab hERG, 542, 544-545 Heterogeneity, 68, 73, 194, 393, 597, 612 Hexokinase, 65 High content screening, 36 High performance liquid chromatography

(HPLC), 12. See also Chromatography High-complexity testing, 465, 471 High-density lipoprotein (HDL), 346, 415, 555-556

High-throughput bisulfite sequencing

(HTBS), 21 Histochemical analysis, 489 Histology, 127, 305, 556, 558, 577, 612 Histopathology, 70, 128, 142, 290-291, 294295, 339, 542, 546, 605, 643 Home brew, 234 Homocysteine, 478

Human epidermal growth factor protein

(HER2), 68, 489, 556, 713 Human Genes Research Act, 631 Human Genome Diversity Project, 626 Human Genome Organization (HUGO), 586, 628

Human Genome Project (HGP), 19, 157, 163, 626

Human Genome Research Law, 631, Human growth factor, 370 Human immunodeficiency virus (HIV), 17, 228, 414-415, 421, 428-429, 466, 554, 582, 700

Human international protein index (IPI), 106

Hypercholesterolemia, 292, 408, 657 Hyperphosphatemia, 306-307, 310-311,

313-314, 316 Hypersensitivity, 331 Hypertension, 115, 366, 371, 408, 415, 657

Ibandronate, 426-427

Icelandic Health Sector Database, 625, 630 Idiopathic membranous neuropathy, 340 Idiosyncratic hepatotoxicity, 439 Idiosyncratic liver injury, 439 Idiosyncratic toxicology reactions, 490 IL-1, 116, 127-130, 404, 612, 614, 616 IL-11, 127-128 IL-15, 129 IL-17, 127 IL-18, 128

ILSI-HESI, see International Life Sciences

Institute Imaging diffusion MRI, 76

dynamic contrast cnhanced-MRI (DCE-

MRI), 68-69, 70-80, 82-84 magnetic resonance (MRI), 9, 18, 38, 43, 704, 710

medical, 16, 19, 43-44, 54-55, 84, 577, 581 myocardial perfusion (MPI), 55-56. nuclear, 45-46, 58, 703 nuclear magnetic resonance (NMR), 9,

44-45, 48, 75, 546 optical, 43, 45 Imatinib, 17, 63, 66, 239, 489, 553, 598, 704.

See also Gleevac Immune system, 121, 130-132, 171-172, 324,

326, 345, 402, 404-405, 414,525 Immunity, 168-169, 171, 333, 404-406, 571, 572

Immunoanalyzer(s), 123 Immunoassay, 12, 108, 122-125, 127, 132, 171, 466

Immunogenicity, 323-333, 405 Immunohistochemical analysis, 349, 489 Immunohistochemical approaches, 150 Immunohistochemical examination, 345, 347 Immunohistochemical localization, 343 Immunohistochemical stain, 233, 344, 558 Immunohistochemical techniques, 476 Immunohistochemistry, 556 Immunoprecipitation, 157 Immunotoxicity, 131 Imprecision, 216, 251, 256 Impurities, 324-326

In vitro diagnostics (IVD), 231-235, 238, 463, 598

Inclusion criteria, 554 Incretin(s), 188

332-333, 342, 440 Infectious disease, 26, 127, 162, 170, 172, 446,

466,471,616 Inflammatory disease(s), 127, 129, 399 Informatics, 18-19, 37, 86-87, 598, 602-603, 618

Informed consent, 109, 242, 390, 469, 625,

627-628, 631-634, 637 Infrastructure, 15-16, 18-20, 25-26, 36, 69, 77, 81, 87, 501, 535, 578, 590, 600, 630, 723 Infringement, 565, 568-573 Ingenuity, 389

Initial new drug (IND), 35, 180, 243, 250, 303, 489,578

Inspection(s), 3-4, 66, 236, 464-465 Institutional review board(s) (IRBs), 32, 35,

114, 470, 508, 600 Instrument detection limit (IDL), 217-218 Integrating the Healthcare Enterprise (IHE), 84

Intellectual property (IP), 15, 26-27, 87, 297,

471,520,523,534 Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), 293 Intercellular adhesion molecule-type 1, 127 Interdisciplinary Pharmacogenomic Review

Group (IPRG), 208 Interference(s), 81, 200, 206, 217-218, 234,

369,468,711,715 Interferon gamma inducible protein (IP-10), 127-128

Interferon gamma release assay(s) (IGRA), 66, 171

Interferon regulating factor 5 (IRF-5), 406 Internal standard, 102, 218, 255, 264, 270, 351

International Conference on Harmonization

(ICH), 183, 230, 290 International Life Sciences Institute (ILSI

HESI), 296, 338, 340, 343, 347 International normalization ratio (INR), 415,

449-457, 459 International Society for Biological and

Environmental Repositories (ISBER), 629

Intersocietal Accreditation Commission

(IAC), 84 Intima media thickness (IMT), 409 Invention, 5-6, 566-572 Investigational New Drug Application (IND), 35, 180, 243, 250, 303, 489

Investigator-Initiated NIH application (R 01), 532

Ischemia, 55, 314, 318, 342, 347-348 Isotope, 7-8, 13, 50, 58, 88, 101

JANUS Data Model, 580, 582 Jorden,4

Juvenile diabetes, 24

Kidney disease, 4, 342-343 Kidney injury, 290-291, 335, 338-340, 342346, 348-351 Kidney injury molecule 1 (KIM-1), 23, 181,

339, 344-346, 348, 350 Kinetica, 419 Kininogen(s), 131-132 K-nearest-neighbour (K-NN), 138, 145 Knock-in, 506 Knock-out, 479, 506 Known valid biomarker(s), 54, 378, 381 Kymograph, 5

Lawsuit, 565, 568, 571-572 LC-MS/MS, 105-107, 111, 115, 557-558 Leave-one-out, 138, 140, 145-146 Left-censoring, 275 Leptin, 114, 188, 415 Leucocyte(s), 10

Leukemia, 17, 138-139, 302, 366, 368, 598, 715, 717

Leukotriene(s), 121, 131-132, 415 Library(s), 163-165, 344, 578 License(s), 58, 151, 468, 471, 523, 570-572, 625

Licensing, 471, 519, 523, 525, 569-570 Ligand(s), 122, 190, 195-196, 201-202, 209210, 365, 369, 418, 479, 599, 705, 710 Ligandin, 343

Limit of blank (LOB), 199-200

Limit of detection (LOD), 103, 116, 199-200,

217, 234, 274-275 Limit of quantitation (LOQ), 217-218 Linearity, 192, 195

477-479, 555-556, 608, 715 Lipocalin(s), 115-116, 348 Liposarcoma, 546

Liquid chromatography-mass spectrometry (LC-MS), 13, 102, 104-107, 111, 114-115, 190, 557

Litigation, 571

Low-density lipoprotein (LDL), 37, 415, 555-556

Lower limit of detection (LLOD), 217-218, 253

Lower limit of quantification (LLOQ), 199200, 217-218, 275 Lowest observed effect levels (LOEL), 541, 543

Luminophore(s), 715 Lymphocyte(s), 17, 128, 131, 612-613, 617 Lymphopenia, 131 Lymphotactin, 127 Lysosomal disease(s), 475-476, 478 Lysosomal-associated membrane protein(s) (LAMP-1, LAMP-2), 477

Macrophage inflammatory cytokine (MIP-

1a), 128, 479 Macrophage inhibitory protein 1 alpha (MIP

1alpha), 128 Macroscopic examination, 290 Macroscopic measurement, 57, 643-647 Macular degeneration, 20, 115 Magnetic resonance imaging (MRI), 9, 18, 38,

43, 704, 710. See also Imaging Major histocompatibility class I, 340 Manometer, 5-6

MAP kinase kinase (MEK), 301-304, 307308, 315, 318 Maraviroc, 428-429, 554 Mass spectrometer, 13-14, 105 Mass spectroscopy (MS), 127, 507 Mass-to-charge ratio (m/z), 105-106 Matrix metalloproteinases (MMP), 129-130,

409,556-557 Matrix-assisted laser desorption ionization

(MALDI), 507 Maximum likelihood estimator (ML), 650, 670

Maximum tolerated dose (MTD), 368 Measurement error, 250-257, 260, 650-651,

666, 668, 670-671 Mechanism of action, 37-38, 77, 113, 131, 142, 188, 190, 302, 363-364, 366, 413, 418419, 440, 485, 504, 506, 606, 695-696, 698

577, 581. See also Imaging Medicare, 84-85, 464-465, 472 Megakaryocyte, 330

Mesothelioma, 63

Metabolomics, 14, 19, 21, 362, 379, 387, 391, 490,598

Metabonomics, 36, 440, 542, 545-547, 551,

556, 559, 577, 607 MetaCore, 389, 606

Method detection limit (MDL), 217-218 Methotrexate, 326, 337, 407, 410, 612, 614 Metronomy, 230

Michigan Economic Development

Corporation, 523 Microbubble ultrasound, 78-81 Microglobulin, 23, 181, 339-340, 346-348 Microsphere, 123, 125-127, 132, 328 Milestone(s), 499, 570, 578-579 Mineralization, 301, 303-319 Minimal Information About Microarray

Experiments (MIAME), 136 Minimum effective dose (MED), 368 Minimum expected difference, 264 Minimum-variance estimator (UMV), 650 MIP-1, 127

Mitogen-activated protein kinase (MAPK), 301

Model-based drug development (MBDD), 414, 416

Molecular biology, 13, 49, 362, 495 Monoclonal antibody(s) (mAb),.17, 167,

323-324,349-350, 507, 596, 612 Monocyte(s), 128, 131, 614 Monocyte chemoattractant protein (MCP-1),

127-128 Monte Carlo, 255-256, 667 mRNA, 136, 163, 165, 188, 341, 344-345, 347,

437, 547, 596, 599, 608, 614, 618 Mucosa, 303, 305-306, 308-310, 312, 314-316 Multiple myeloma, 24, 205, 207, 510 Multiple sclerosis (MS), 18, 48, 127, 330, 698,

701, 704, 706 Multivariate, 107, 122, 127, 130, 348, 388, 598,

648-649,654, 663-664 Mutation(s), 27, 164, 236, 239, 256, 276, 362, 364,388,466-467,470-472, 547, 553554, 569, 584, 597, 634, 716, 719 Myasthenia gravis, 366, 369 Myocardial perfusion imaging (MPI), 55-56.

See also Imaging Myocardium, 55, 76, 306, 314 Myoglobin, 293, 719

N-acetyl-beta-glucosaminidase (NAG), 340, 342

Nanoarray(s), 719-721

Nanocantilever(s), 718-719, 721 Nanodevice(s), 709-710, 716, 721-723 Nanodiamond(s), 715, 722 Nanoelectrode(s). 720-721 Nanoparticle(s), 710, 714-716, 722 Nano-PEBBLE, 715, 722 Nanoscale, 709, 715-716, 721-722 Nanotechnology, 19, 709-710, 721-723 Nanotoxicology, 710, 721-723 Nanowire(s), 716-718, 721 National Cancer Institute (NCI), 3, 62, 66, 84,

86-87, 580, 632 National Cancer Institute of Canada, 62 National Center for Biotechnology

Information, 21 National Committee for Clinical Laboratory

Standards (CLSI), 199-200, 208, 234 National Heart Lung and Blood Institute, 27 National Institutes of Health (NIH), 18, 23, 85, 88, 161, 163, 172, 210, 231, 505, 516-517, 519-520, 527-529, 532,628, 695

National Library of Medicine, 21 National Research Council, 529-530 National Science Foundation (NSF), 527-528 Negative predictive value (NPV), 107, 116,

181,219-221, 224-225, 659 Neoplasia, 301, 308 Neopterin, 415, 425 Nephrectomy, 342

Nephrogenic systemic fibrosis (NSF), 73 Nephrotoxic agents, 142-143 Nephrotoxic compounds, 142-144 Nephrotoxic effects, 344 Nephrotoxic side effects, 351 Nephrotoxicity, 142-143, 180, 182, 205, 296, 338-340,342-344, 346-347, 350-351 Nervous system, 23, 127, 193, 303, 341, 566,

370, 440, 479, 506, 545 Neurotoxicity, 317, 370 Neurotransmitter, 370-371 Neutralization, 129, 329 Neutralizing agent(s), 369 Neutralizing antibody(s), 115, 329 Neutrophil(s), 131, 310, 348 Neutrophil gelatinase-associated lipocalin

(NGAL), 115, 339, 348-350 New Drug Application(s) (NDAs), 180, 231, 578

No-adverse effect level(s) (NOAEL), 34, 306,

541, 543 Nobel Prize, 7, 10, 13 No-effect level(s) (NOEL), 312, 541, 543

Nonequilibrium, 644, 648-649 NONMEM, 419 Non-obvious, 363, 567 Nonparametric test(s), 268-270 Non-responder(s), 17, 38, 138, 145-146, 227, 611, 705

Non steroidal anti-inflammatory drugs

(NSAIDS), 336-337, 410 Norbuprenorphine, 423-424 Normal distribution, 206, 269, 273 Normalization, 103, 193, 264, 278, 311, 449, 455-456

Norwegian Act on Biobanks, 631 N-terminal poly-polyHistidine (polyHis) tag, 167

Nuclear imaging, 45-46, 58, 703. See also Imaging

Nuclear magnetic resonance (NMR), 9,

Null hypothesis, 247, 266, 271, 280, 657 Nuremberg Code, 632

Odds ratio (OR), 220-222, 224-225, 237, 266267, 276-277, 283, 403,614,618 Office for Human Research Protection

(OHRP), 631, 633 Office of Combination Products (OCP), 241243, 245

Office of In Vitro Diagnostic Devices and

Safety (OIVD), 234-236 Oligonucleotide(s), 136, 720 Oligosaccharide(s), 477 Omics, 13-14, 559 Oncogene(s), 301, 364, 597 Oncogenicity, 301, 364, 368, 370, 599 Oncologics, 543, 547 Oncotype DX, 141, 150-151 Online Mendelian Inheritance in Man

(OMIM) database, 612 Open Bioinformatics Foundation, 86 Open reading frames (ORFs), 161-166, 169, 172

Operational Data Mode(l) (ODM), 580 Optical imaging, 43, 45. See also Imaging Optimization, 50, 55, 58, 60, 75, 110, 179, 259,

438, 499, 660, 663-664, 689, 694, 722 Ordinary least-square(s) (OLS), 650 Osteoarthritis, 18, 38, 86, 557-558, 701, 704 Osteoarthritis Initiative (OAI), 86 Osteoblast(s), 308

Osteocalcin, 188, 308-310, 315-316, 703 Osteopontin (OPN), 339, 347

Osteoporosis, 205, 207, 427, 701-704 Outlier(s), 271, 274 Outsourcing, 496, 518-519 Ovarian cancer, 23, 25, 63, 110-111, 130, 161, 171

Overexpression, 171, 250, 607 Ovulation, 11

Pamidronate, 304, 311-312, 337 Pancreas, 343, 347-348 Parallelism, 194-195, 200, 209 Parametric test(s), 268-270, 272, 283 Parathyroid hormone (PTH), 306-308, 313 Patent, 10, 289, 390, 471, 520, 529, 565-573 application, 471, 566-568 attorney, 567, 570-571 Patent Cooperation Treaty (PCT), 568 Pathobiology, 36, 155, 510 Pathodynamics, 643, 645-648, 654, 688-689 Pathogenesis, 400-402, 408, 486-488, 594, 611 Patient progress, 188

selection, 38, 179, 241, 364, 372, 390, 392 stratification, 60, 188-189, 376, 489, 505-507 Pattern recognition, 25, 101, 127 Patterning, 121-122, 127, 132-133 Pegylation, 326

Peroxisome proliferator-activated receptor

(PPAR), 188, 459, 545, 610 Personalized medicine(s), 25, 122, 250, 280281, 489, 499, 523, 556, 590, 593-595. 598-599, 605,613, 616-618 Pharmaceutical Research and Manufacturers of America (PhRMA), 85, 693 Pharmacogenetic(s), 416, 489, 554, 594, 609 Pharmacogenomic(s), 19, 232, 235, 239, 244,

250, 280, 362, 584, 628-629, 635 Pharmacokinetic(s), 80, 190, 319, 333, 413414, 418, 420, 424, 496, 665 Pharmacotherapeutic decision, 24 Phenotype, 21, 25, 126, 224, 363, 477, 593, 595, 597-600, 605, 608-609, 611, 618, 696

Philadelphia chromosome, 17, 368, 489, 553

Phospholipid(s), 415, 440-441, 555

Phospholipidosis (PLD), 439-441, 452

Phosphorescence, 7

Phosphorus, 9, 301, 303, 305-319

Photobleaching, 715

Picture Archiving and Communications

Systems (PACS), 582 Piezo-electric, 124, 159 Pioglitazone, 610

Pipeline(s), 16-17, 367, 491, 518 Pituitary, 343

Plasminogen activator inhibitor type 1, 130 Platelet(s), 10, 131, 366, 369-370, 449, 696 Polycystic kidney disease, 342 Polyethylene glycol (PEG), 326, 424-425, 712 Polymerase chain reaction (PCR), 18, 136137, 145, 149, 156, 164-166,171,344, 378,386,472,547,717 Polymorphism(s), 20-21, 236, 275, 364, 403, 406, 471, 490, 568, 608, 610, 612, 614615, 618,721 Pompe's disease, 24, 476-477 Population enrichment, 60 Positive predictive value (PPV), 219-221, 225, 650,659

Positron emission tomography (PET), 8, 18, 43-46, 48, 58, 60-62, 66-68, 75, 80-81, 86, 425-426, 703-705, 712. See also Tomography Post-analytic factors, 471 Post-analytic testing, 468 Post-market applications, 180 commitments, 241 data, 491 decisions, 37 drug use, 422 patient monitoring, 188 reporting, 233 surveillance, 233, 382, 578 trials, 383, 451, 490, 702 Practical quantitation limit (PQL), 217-218 Pre-analytic circumstances, 192 Pre-analytic factors, 191, 202, 471 Pre-analytic testing, 466-467 Pre-analytic variables, 192 Pre-biomarker(s), 52 Predictability, 138, 327, 362, 438-439, 477 Predictive Safety Testing Consortium (PSTC),

181-182, 296 Pre-IND, 243

Pre-Investigational Device Exemption (pre-

IDE), 235-236, 241, 243 Premarket approval (PMA), 233-236, 241 Prevalence, 220-221, 224, 228, 240, 383, 439,

654, 656 Primate(s), 327, 340 Prior art, 365, 566-568 Prioritization, 36, 602, 605-606 Probabilism, 645-646

Probable valid biomarker(s), 54, 296, 378, 381 Proficiency testing (PT), 465-466

171,233,282,34G,4G1-4G2,446,464 Project management, 85, 495-496, 5G1-5G2,

51G-511 Projection(s), 541, 543, 548 Prontosil, 289

Proof of concept, 24, 37, 65, 24G, 364, 377, 41G, 429, 491, 517,521,541,579,7G1 Proof-of-efficacy, 489 Proof-of-feasibility, 6G2 Proof-of-mechanism, 57, 6G, 189 Proof of principle, 161, 477, 488 Proof-of-therapeutic-concept, 6G Proportional data, 266, 27G Prostate cancer, 114-115, 162-163, 2G6, 523-

524,7G5,713 Prostate-specific antigen (PSA), 114, 188, 233,

395,523,718-719 Protein Identification and Peptide Expression

Resolver (PIPER), 1G6 Protein phosphorylation, 3G2 Proteinuria, 4, 337, 34G, 346 Protesome. 51G

Prothrombin time (PT), 447, 449, 451-454

Proximal tubular cell(s), 34G, 343

P-selectin, 366-369

Public Library of Science, 23

Public Population Project in Genomics consortium (P3G), 631-632 PubMed, 3, 582, 629 Pulmonary and activation-regulated chemokine (PARC), 479-48G Purified protein derivative (PPD), 171

QT prolongation, 545 Quality assurance (QA), 168, 378, 383, 391-392

Quality control (QC), 49, 55, 73, 84, 1G3, 124, 156, 198, 2G3-2G4, 235, 255, 278, 391393, 6G2

Quantitation, 121-122, 124, 145, 217-218, 26G,

274-275, 344, 413 Quantitative Imaging Biomarkers Alliance

Radiation, 6-8, 58-59, 76, 78-79, 81, 524 Radioactivity, 7, 12 Radioimmunoassay, 7, 12, 343-344 Radiological Society of North America

Rash(s), 317-318, 331-332, 337 Reactive intermediate(s), 439-440 Reagan-Udall Foundation, 23 Real time PCR (RT-PCR), 171, 190, 547 Receiver operator characteristic (ROC), 107,

111, 220, 222, 394, 660 Receptor signaling, 403, 713 Recombinant DNA, 16-17, 19 Red blood cell(s), 10, 131-132, 337 Reference laboratory(s), 466, 472, 520, 552, 556, 559

Reference range(s), 310, 315, 456, 468 Reference standard(s), 193-194, 196-198, 204,

208-209,251,255, 257 Registration, 53, 56, 60, 233, 364, 366, 464,

489-491,496,507, 693, 706 Regulatory approval, 38, 179, 229, 376, 395,

505, 509, 539, 565, 694 Regulatory submission(s), 63, 180, 230, 338, 349, 701

Relative risk, 31, 33, 224, 266, 406, 409, 700 Relative toxicity, 594

Relevance, 20, 57, 146-149, 196, 220, 250, 255, 259, 291, 348, 363, 413, 435, 439, 479, 504, 508, 548, 664, 698 Reliability, 49, 51, 59, 77, 144, 193, 224, 446,

448, 628, 698 Renagel, 304, 311 Renal clearance, 306 Renal cortical tubule(s), 305 Renal failure, 335, 342, 348, 371 Renal function, 74, 79, 338, 340, 342, 346, 351 Renal papillary antigen 1 (RPA-1), 339-340,

349-351 Renal transplantation, 340 Rennin, 371 Repeatability, 216, 234 Repository(s), 18, 197, 210, 582, 586-589,

629-630, 632 Reproducibility, 25, 70-71, 124, 126, 132, 148, 196, 198, 216, 234, 382, 387, 391, 393, 588-589, 698, 716, 722 Research plan, 530

104, 409, 506, 720 Responder(s), 17, 24, 38, 138, 145-146, 227, 489, 547, 578, 611, 616, 618, 677, 705 Response Evaluation Criteria in Solid

Tumors (RECIST), 61-65, 78, 607 Return on investment (ROI), 31, 33, 67, 376, 704

Reverse pharmacology, 362 Rhabdomyolysis, 292, 337 Rheumatoid arthritis (RA), 127-129, 187, 192, 205-207,309, 399,400, 403,406407, 415, 486, 544, 595, 611, 614-615, 618, 704 RIA, 329

Risk assessment, 24, 32-33, 38, 368, 406, 423, 441, 545

Risk-benefit, 33, 318, 700. See also Benefit/

Risk and Risk/Cost Benefit Risk/cost benefit, 501. See also Benefit/risk and Risk-benefit Rituximab, 331, 410, 612 RNA, 13, 128, 136, 138-140, 142-143, 145146, 148-149, 348, 421, 542, 554, 598, 613, 700

Robustness, 77, 196, 198, 209-210, 257, 259, 362, 386-388, 392, 506, 541, 558, 598, 698

Rosuvastatin, 556. See also Statins Royalty payment(s), 570 RPA-1, 184, 339-340, 349, 350-351 Rural Advancement Foundation International (RAFI), 626

S-ADAPT, 419

Safety assessment, 289-290, 346, 496 Safety margin(s), 371, 445, 541, 543-545 Safety pharmacology, 303-304 Safety profile, 52, 237, 240, 369, 448, 459, 616, 618

Sample size, 25, 51, 149, 192, 220, 260-261, 264, 275, 376, 384-387, 390, 394, 645, 650, 658, 664, 677, 709 Sandwich immunoassay, 123 Scleroderma, 128 Secretome, 113, 116 Self antigen(s), 324-325, 331, 405 Sematech, 296, Sepsis, 192, 355, 522

276, 488, 610, 629 Sertoli cell(s), 341 Serum amyloid A, 129 Serum sickness, 330-331 Service Oriented Architecture (SOA), 583, 588-590

Severe toxicity (or death) in 10% of the rodents (STD10), 316 Siderocalin, 348

Signal transduction, 301-302, 308, 315, 403, 504

Significance Analysis for Microarrays (SAM), 137

Simulation, 256, 364, 414, 416, 418, 420, 422423, 429, 667, 671,672 Simvastatin, 556. See also Statins Single nucleotide polymorphism (SNP), 20,

364, 403, 490, 568, 608, 612, 721 Single photon emission computed tomography (SPECt), 8, 38, 43-44, 55-56, 58, 67, 703-704. See also Tomography Sjogren's syndrome, 129, 407 Small Business Innovative Research (SBIR),

523, 527-530, 532, 534-539 SNP consortium, 20

Solution for Compliance in a Regulated

Environment (SCORE), 582-583, 588 Source of error, 251

SParse Linear Programming (SPLP), 143 Species difference(s), 446 Sphygmomanometer, 5-6 Sphygmomètre, see Sphygmomanometer Spiking, 194, 198, 201 Sprycel, 553 Stacking, 122

275,456-457 Standard deviation, 199-200, 205, 207, 216219, 247, 260-262, 264, 268-270, 650, 660-661, 667 Standard for Exchange of Non-clinical Data

(SEND), 579 Standard operating procedure (SOP), 103, 202, 383, 386, 391, 509, 585, 588, 600 Standardized operating protocol (SOP), see

Standard operating procedure Standardization, 44, 53, 57, 61, 66-67, 70, 75-76, 82-85, 87-88, 193, 210, 632 Standard-of-care, 226-228, 295, 368, 602 Statin(s), 225, 292, 555-556 atorvastatin, 556 rosuvastatin, 556 simvastatin, 556. Statistical analysis, 18, 83, 162, 204, 248-249,

259, 263, 268, 274, 279, 282, 505 Statistical power, 207, 250, 260, 262, 264, 274275,279

Statistical significance, 37, 225, 250, 256, 271, 505

Stomach, 308, 312, 315, 319, 341, 348, 415 Stratification, 24, 26, 60, 179, 188-189, 215, 226, 238, 241, 276, 363, 376, 400, 489, 505-507, 554, 556

Stratified approach(s), 379, 389 Stratified medicine, 590 Stratified model, 577 Stratified patient care, 590 Stratified patient population(s), 578 Stratified therapy, 507 Stratified tools, 379

Study Data Tabulation Model (SDTM), 580, 582-586

260, 263, 290, 394, 417, 425, 501 Subcutaneous adipose tissue, 115 Subcutaneous administration, 326, 424, 447 Sulfanilamide, 289-290, 337 Sulfated glycoprotein-2 (SG-2), 341 Supporting vector machine (SVM), 137, 139, 145

Sweden's Act on Biobanks, 631, 557 SwissProt, 582, 587 Synovial fluid, 401-402 Systemic lupus erythematosus (SLE), 127, 403,615

Systems biology, 19, 36, 488, 545, 598-600, 606

T cell immunoglobulin and mucin domain-containing protein 1 (TIMD-1), 345 Tamm-Horsfall protein(s), 346 Tamoxifen, 141

Target product profile (TPP), 33, 35

Target selection, 362, 368

Target validation, 24, 363, 365-366, 369, 372,

416, 445,694 Tasigna, 553 Testis, 341, 343, 506

Testosterone-repressed message-2 (TRPM-2), 341

TGN1412, 131

T-helper lymphocyte(s), 408, 554 Therapeutic agent(s), 22, 33, 292, 318, 485,

487-488, 535, 565, 596, 613 Therapeutic effect(s), 57, 488, 655, 689 Therapeutic index, 363, 368, 370-371, 442,

543,547,594,596 Therapeutic intervention^, 68, 128, 130, 192, 280, 338, 350, 371, 376, 433,446-447, 479, 490, 505, 610, 649, 695, 697, 705 Thiazolidinedione, 439, 607 Thrombin, 371, 447, 449, 478 Thrombocytopenia, 330, 336 Thromboplastin, 447, 450-456 Thrombosis, 366, 369, 449 Time-of-flight (TOF), 13, 104

TIMP-1, 130 Tissue typing, 463 Titer(s), 130, 329-330 Tocilizumab, 129, 612-613, 616 Tolerance, 189, 193, 323-324, 326, 328, 331333, 363, 370, 437, 611 Tomography. 7-8, 18, 38, 43, 425, 703

positron emission (PET), 8, 18, 43-46, 48, 58, 60-62, 66-68, 75, 80-81, 86, 425426, 703-705, 712 single photon emission computed (SPECT),

8, 38, 43-44, 55-56, 58, 67, 703-704 x-ray computed (CT), 38, 43 Total protein, 23, 104, 181, 305 Toxicant signature, 142 Toxicogenomics, 143, 304, 306, 312, 316, 547 Toxicokinetic, 304, 306, 312, 316 Tracers, 46-47, 67-68, 82, 84 Trachea, 348

Transcriptomics, 440, 544-545, 608 Transformed data, 269, 273 Transgenesis, 328 Transgenic mice, 47, 328, 332 Translational component, 517 Translational research, 16-17, 21, 25, 496-499 Trastuzumab, 239, 489, 507, 556, 596. See also

Herceptin Trefoil factor, 23, 181 Triglyceride(s), 506, 555, 700 True negative(s) (TN), 220-222, 224, 658-659 True positive(s) (TP), 219-222, 224, 254, 259, 658

Tuberculosis (TB), 162-163, 170-172, 233 Tubular damage, 342, 344, 346-348, 350 Tubular necrosis, 337-338, 345, 347 Tumor necrosis factor (TNF), 128, 404, 415 Tumorigenesis, 302, 597 Tyrosine kinase(s), 17, 75, 250, 301, 314, 368, 718

Tyrosine kinase inhibitor(s), 75, 553 Tyrosine kinase receptor, 17

UK Human Tissue Act, 631 Ulcerative colitis, 127 Ultracentrifugation, 555 Ultrasonic characteristics, 9 Ultrasonic diagnosis, 8 Ultrasonic equipment, 8 Ultrasonic reflectoscopes 8 Ultrasound, 8-9, 43, 45-47, 62, 78-81, 337, 409, 701, 703, 715

Unicorn, 551-553

United States Patent and Trademark Office

(USPTO), 566-568, 570 Univariate, 664-665

Universal Declaration of Human Rights, 632 University of Michigan, 515-516, 521-523,

525,529 Unlinking, 634 Urinalysis, 306, 308, 310 Uroprontin, 347 Uroscopy, 3-4 Urticaria, 331

US National Bioethics Advisory Commission, 629, 631

Vascular cell adhesion molecule (VCAM-1), 128

Vascular endothelial growth factor, 47 Vasculature, 128, 292, 303, 305, 312, 545, 602 Vasculitis, 407-408, 545 Very low-density lipoprotein (VLDL), 555 Viral load, 17, 414-415, 428-429, 696 Vitamin D, 306-307, 310-311, 313-316, 318 Voluntary data submission (VXDS), see Voluntary eXploratory Data Submissions Voluntary eXploratory Data Submissions

(VXDS), 180-181, 208, 380 Voluntary genomic data submissions

(VGDS), 243 Voluntary submission, 22, 180, 508, Von Willebrand factor, 128

Waived category, 465 Waived test, 465

Weight of evidence, 281, 346, 413, 416 Weighted voting (WV), 137-138, 145-146 WinNonlin, 419 Workplan, 532

World Health Organization (WHO), 61-63, 450

X-ray, 6-9, 28, 43-45, 524, 701, 703-704 X-ray computed tomography (CT), 38, 43. See also Tomography

YKP1358, 425-426

Assay validation

Clinical qualification

Clinical Endpoint

Image-based Measure

Biological Function or

Disease Process

Clinical Endpoint

Chapter 4, Figure 2 Two-step process for imaging biomarker validation/qualification. Assay validation establishes the link between the image-based measure and a specific biological function or disease process by way of a biological, biophysical, or molecular "model." This includes characterizing the measurement's intra- and interobserver and test-retest variability (measurement reliability), as well as correlating the measurement to an established (nonimaging or invasive) standard. The goal of the second step, clinical qualification, is to establish empirically, by clinical trials, the relationship between the image-based functional measure and a relevant clinical endpoint or outcome.

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