Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease (2010) / Chapter Skim
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Glossary
Glossary
Pages 239-252
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From page 239... ...
Glossary Ablation -- the removal of a body part or the destruction of its function, as by a surgical procedure, morbid process, or noxious substance Accelerated approval -- regulatory mechanism by which new drugs meant to treat serious, life-threatening diseases or diseases for which there are no alternative treatments can be approved for marketing by the Food and Drug Administration using earlier clinical trial results than would be required for regular approvals; post-market surveillance and studies generally required ACE inhibitor -- see Angiotensin-converting enzyme (ACE) inhibitor Adenomatous colon polyps -- growths in the epithelial layers of the colon; can be flat, pedunculated, or sessile; result from multiple genetic mutations arising from environmental or inherited causes; can become cancerous Adhesion molecules -- molecules on cell surfaces that enable cells to stick to each other or other components of the extracellular matrix Adjusted association -- a measure of association between individual patients' true endpoints and surrogate endpoints after controlling for treatment assignment; a statistical method for surrogate endpoint evaluation Age-related macular degeneration -- a disease occurring when the cells making up a central area of the retina, called the macula, break down or move away from their normal positions; causes blurriness and some times loss of the center of field of vision
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From page 240... ...
Angiotensin-converting enzyme (ACE) inhibitor -- drug used to treat blood pressure; prevents formation of a protein that causes constriction of blood vessels, thus lowering blood pressure Angiotension receptor blocker -- type of medication used to treat high blood pressure.
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From page 241... ...
-- specialized cells that play a role in measuring immune response in individuals with HIV Choi criteria -- a measure used to assess tumor progression in gastrointes tinal stromal tumor (GIST) ; incorporate tumor size and tumor density into a metric of tumor progression; demonstrated to more accurately predict overall survival in GIST than reduction in tumor size Cholesterol -- abundant steroid metabolite produced by animals and found in cell membranes and circulating in blood; excess cholesterol can lead to fatty deposits in blood vessels, a risk factor for cardiovas cular disease Chromium picolinate -- biologically active chromium salt that is used as a dietary supplement Chronic disease -- a culmination of a series of pathogenic processes in response to internal or external stimuli over time that results in a clini cal diagnosis/ailment and health outcomes Clinical endpoint -- a characteristic or variable that reflects how a patient feels, functions, or survives (Biomarkers Definitions Working Group, 2001)
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From page 242... ...
Any laboratory-based test that can be used in drug discov ery and development as well as in patient care and clinical decision making (IOM, 2007) Diastolic blood pressure -- blood pressure as measured during the resting phase of the heart's rhythm Dietary guidance statement -- a statement describing general dietary pat terns, practices and recommendations that promote health; these make reference to categories of foods and not specific substances, and they do not describe relationships between a substance (specific food or food component)
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From page 243... ...
Friedewald formula -- provides an estimate of LDL cholesterol for most fasting specimens, though its accuracy is lower at higher triglyceride concentrations. genomics -- the study of all of the nucleotide sequences, including struc tural genes, regulatory sequences, and noncoding DNA segments, in the chromosomes of an organism or tissue sample.
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From page 244... ...
-- a lipoprotein of blood plasma that is composed of a high proportion of protein with little triglyceride and cholesterol and that is associated with decreased prob ability of developing atherosclerosis Hill criteria -- criteria used to establish cause in the case of non-infectious or chronic disease by evaluating strength, consistency, specificity, tem porality, biological gradient, plausibility, coherence, experiment, anal ogy; used in environmental health, toxicology, pharmacology, epide miology, and medicine Hyperlipidemia -- the presence of abnormally high amount of lipids in the circulating blood Hypertension -- abnormally high arterial blood pressure that is usually indicated by an adult systolic blood pressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hg or greater; can result in thick ening and inelasticity of arterial walls and damage to the heart; a risk factor for various pathological conditions or events (e.g., heart attack, heart failure, stroke, end-stage renal disease, or retinal hemorrhage) Immune response -- response of an organism to a foreign substance Immunoassay -- test measuring the immune response of an organism to an antigen In vitro -- outside the living body and in an artificial environment In vivo -- in the living body of a plant or animal Incidence -- occurrence of a disease or condition Inflammatory biomarker -- biological chemicals indicating tissue damage or irritation; C-reactive protein is an inflammatory biomarker
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From page 245... ...
Intervention -- any drug, device, biologic, behavioral modification, nutri tional modification, lifestyle modification, or other treatment intended to improve health Intima-media thickness (IMT) -- the thickness of the inner layers of an artery Ischemic stroke -- stroke caused by thrombosis or embolism; caused by an inadequate flow of blood to heart tissue due to a constriction or block age to blood vessels supplying it Lipoprotein -- compounds containing lipid and protein; almost all lipids in plasma are lipoproteins Low-density lipoprotein cholesterol (LDL-C)
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From page 246... ...
in a miniature arrange ment; DNA microarrays most commonly used (IOM, 2007) Myocardial infarction -- an acute episode of heart disease marked by the death or damage of heart muscle due to insufficient blood supply to the heart muscle, usually as a result of a coronary thrombosis or a coronary occlusion and that is characterized especially by chest pain Myxoid degeneration -- a degenerative process in which the connective tissues are replaced by a gelatinous or mucoid substance Neural tube effects -- a group of birth defects that involve the central ner vous system; result from failure of the neural tube to properly form Normal sinus rhythm -- normal heart rhythm Null hypothesis -- the hypothesis that an intervention has no effect (i.e., that there is no true difference in outcomes between a treatment group and a control group)
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From page 247... ...
The Food and Drug Administration generally requires new drugs to be tested in phase III trials before they can be put on the market (IOM, 2007) Phospholipid -- any of numerous lipids in which phosphoric acid as well as a fatty acid is esterified to glycerol and which are found in all living cells and in the bilayers of cell membranes Phytosterol -- cholesterol-like compounds found in vegetable oils, nuts, and legumes; may reduce serum cholesterol Plaque -- a well-demarcated yellow area or swelling on the surface of the artery; produced by intimal lipid deposit Plasma -- the fluid portion of the circulating blood Pleiotropic effects -- having multiple phenotypic expressions; for exam ple, the non-lipid effects of statins, including the anti-inflammatory and antithrombotic properties that contribute to an improvement in vascular function Polymorphism -- occurrence in the same population of two or more geno types of such proportion that the most rare cannot be maintained by recurrent mutation alone; heritable variations in low-density lipo proteins; variant lipoproteins exhibit different antigenic and chemical properties compared with normal lipoproteins Positive harm -- something that is intended to do good is not only ineffec tive, but causes definite harm as an unintended side effect Positive predictive value -- the probability that an individual with a posi tive test has, or will develop, a particular disease, or characteristic, that the test is designed to detect; a measure of the ratio of true positives to (false + true positives)
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From page 248... ...
Postmarket studies -- may be mandated by the Food and Drug Admin istration for already approved drugs or devices to review potential risks Precision -- a measure of random error; inversely related to random error; confidence intervals are computed to demonstrate the precision of rela tive risk estimates Predictive value -- the ability to predict the change in the outcome of a disease given a particular intervention using a specified patient measurement Prentice criteria -- stringent requirements to be met before a biomarker can definitively substitute for a clinical endpoint for a given use; briefly, the criteria state that a biomarker must perfectly correlate with the clinical outcome it is meant to replace and capture the entire effect of the intervention used to bring about the effect on the clinical outcome Prevalence (disease) -- the number of existing cases of a disease in a given population at a specific time Prevention -- the use of medical and public health tools to prevent dis ease, injury, or other events injurious to health Prognosis -- an assessment of the probable course of a disease given the risk factors present in an individual; this assessment may affect treat ment decisions Prognostic value -- the ability to predict disease outcome or course using a specified patient measurement Protease -- biological chemical that reacts with proteins, degrading them chemically and making them non-functional Proteomics -- the study of the structure, function, and interactions of the proteins produced by the genes of a particular cell, tissue, or organism.
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From page 249... ...
Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best Relative effect -- the effect of a treatment on the distribution of true end points versus surrogate endpoints; component of a statistical method for surrogate endpoint evaluation Relative risk -- the ratio of the risk of disease in exposed individuals to the risk of disease in non-exposed individuals Risk–benefit analysis -- the comparison of the risk of a situation to its benefits Risk biomarker -- biomarker that indicates a component of an individu al's level of risk for developing a disease or level of risk for developing complications of a disease Risk stratification -- the classification of patients into groups based on the likelihood of developing or suffering effects from a disease Safety biomarker -- a biomarker that can be used to identify patients at high risk for serious side effects, to monitor early signs of toxicity, or to predict the likelihood for severe toxicity Sample bias -- see Bias Saturated fat -- fat having no double bonds; chemically the most stable type of fat; solid at room temperature; come chiefly from animal food products; tend to raise the level of cholesterol in the blood Screening -- the use of risk factor analysis and biomarker assays to detect early-stage disease in the asymptomatic population Sensitivity (analytical)
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From page 250... ...
Surrogate threshold effect -- the minimum treatment effect on the sur rogate endpoint necessary to predict a non-zero effect on the true end point; provides information relevant to the practical use of a surrogate endpoint and can be interpreted from a clinical point of view Surveillance -- population-level monitoring for early detection and treat ment of advancing disease or complications Systolic blood pressure -- the highest blood pressure that occurs during a beat of the heart, just after the left ventricle has contracted Target validation -- demonstration that a potential drug target plays a key role in the disease process Therapeutic intervention -- actions taken (through administration of a drug or other means) to treat a disease or other health-related condition
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From page 251... ...
True endpoint -- the endpoint for which a surrogate endpoint is sought Tumor response rates -- in its most primitive form: tumor shrinkage; defined by a change in tumor bulk; commonly used for making deci sions regarding approval of anticancer drugs in the 1970s Tumor size -- inconsistently defined biomarker often used for determining efficacy of cancer therapeutics Type 2 diabetes -- diabetes mellitus of a common form that develops especially in adults and most often in obese individuals and that is characterized by hyperglycemia resulting from impaired insulin utili zation coupled with the body's inability to compensate with increased insulin production ultracentrifuge -- a high-speed centrifuge by means of which large mol ecules (proteins, nucleic acids) are caused to sediment at practicable rates; used for determination of molecular weights utilization -- contextual analysis based on the specific use proposed and the applicability of available evidence to this use.
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From page 252... ...
2002. Overview of biomarkers and surrogate endpoints in drug development.
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