Clinical Trials as Topic
Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.
Clinical Trials, Phase I as Topic
Works about studies performed to evaluate the safety of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in healthy subjects and to determine the safe dosage range (if appropriate). These tests also are used to determine pharmacologic and pharmacokinetic properties (toxicity, metabolism, absorption, elimination, and preferred route of administration). They involve a small number of persons and usually last about 1 year. This concept includes phase I studies conducted both in the U.S. and in other countries.
Clinical Trials, Phase III as Topic
Works about comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.
Clinical Trials, Phase II as Topic
Works about studies that are usually controlled to assess the effectiveness and dosage (if appropriate) of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques. These studies are performed on several hundred volunteers, including a limited number of patients with the target disease or disorder, and last about two years. This concept includes phase II studies conducted in both the U.S. and in other countries.
Maximum Tolerated Dose
Drug Administration Schedule
Controlled Clinical Trials as Topic
Works about clinical trials involving one or more test treatments, at least one control treatment, specified outcome measures for evaluating the studied intervention, and a bias-free method for assigning patients to the test treatment. The treatment may be drugs, devices, or procedures studied for diagnostic, therapeutic, or prophylactic effectiveness. Control measures include placebos, active medicines, no-treatment, dosage forms and regimens, historical comparisons, etc. When randomization using mathematical techniques, such as the use of a random numbers table, is employed to assign patients to test or control treatments, the trials are characterized as RANDOMIZED CONTROLLED TRIALS AS TOPIC.
Dose-Response Relationship, Drug
Antineoplastic Combined Chemotherapy Protocols
Randomized Controlled Trials as Topic
Multicenter Studies as Topic
Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.
Clinical Trials Data Monitoring Committees
Committees established to review interim data and efficacy outcomes in clinical trials. The findings of these committees are used in deciding whether a trial should be continued as designed, changed, or terminated. Government regulations regarding federally-funded research involving human subjects (the "Common Rule") require (45 CFR 46.111) that research ethics committees reviewing large-scale clinical trials monitor the data collected using a mechanism such as a data monitoring committee. FDA regulations (21 CFR 50.24) require that such committees be established to monitor studies conducted in emergency settings.
Combined Modality Therapy
Clinical Trials, Phase IV as Topic
Planned post-marketing studies of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques that have been approved for general sale. These studies are often conducted to obtain additional data about the safety and efficacy of a product. This concept includes phase IV studies conducted in both the U.S. and in other countries.
Area Under Curve
A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)
Metabolic Detoxication, Phase I
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
Drug Therapy, Combination
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Quality of Life
Antineoplastic Agents, Phytogenic
Severity of Illness Index
Outcome Assessment (Health Care)
Antibodies, Monoclonal, Humanized
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results.
An approach of practicing medicine with the goal to improve and evaluate patient care. It requires the judicious integration of best research evidence with the patient's values to make decisions about medical care. This method is to help physicians make proper diagnosis, devise best testing plan, choose best treatment and methods of disease prevention, as well as develop guidelines for large groups of patients with the same disease. (from JAMA 296 (9), 2006)
Drug-Related Side Effects and Adverse Reactions
Reproducibility of Results
The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.
Nontherapeutic Human Experimentation
Therapeutic Human Experimentation
Metabolic Clearance Rate
Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)
Neoplasm Recurrence, Local
Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.
Data Interpretation, Statistical
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Carcinoma, Non-Small-Cell Lung
Drug Evaluation, Preclinical
Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.
United States Food and Drug Administration
Molecular Targeted Therapy
A nonparametric method of compiling LIFE TABLES or survival tables. It combines calculated probabilities of survival and estimates to allow for observations occurring beyond a measurement threshold, which are assumed to occur randomly. Time intervals are defined as ending each time an event occurs and are therefore unequal. (From Last, A Dictionary of Epidemiology, 1995)
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)
Intention to Treat Analysis
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
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.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
Meta-Analysis as Topic
A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Drug Resistance, Neoplasm
National Cancer Institute (U.S.)
Analysis of Variance
A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior.
Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).
Guidelines as Topic
A systematic statement of policy rules or principles. Guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by convening expert panels. The text may be cursive or in outline form but is generally a comprehensive guide to problems and approaches in any field of activity. For guidelines in the field of health care and clinical medicine, PRACTICE GUIDELINES AS TOPIC is available.
Antineoplastic Agents, Alkylating
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
Ethics Committees, Research
Predictive Value of Tests
In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.
Practice Guidelines as Topic
Directions or principles presenting current or future rules of policy for assisting health care practitioners in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery.
An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.
A class of statistical methods applicable to a large set of probability distributions used to test for correlation, location, independence, etc. In most nonparametric statistical tests, the original scores or observations are replaced by another variable containing less information. An important class of nonparametric tests employs the ordinal properties of the data. Another class of tests uses information about whether an observation is above or below some fixed value such as the median, and a third class is based on the frequency of the occurrence of runs in the data. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1284; Corsini, Concise Encyclopedia of Psychology, 1987, p764-5)
Any deviation of results or inferences from the truth, or processes leading to such deviation. Bias can result from several sources: one-sided or systematic variations in measurement from the true value (systematic error); flaws in study design; deviation of inferences, interpretations, or analyses based on flawed data or data collection; etc. There is no sense of prejudice or subjectivity implied in the assessment of bias under these conditions.
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Drug Delivery Systems
Metabolic Detoxication, Phase II
The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.
National Institutes of Health (U.S.)
A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
Sensitivity and Specificity
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.
Translational Medical Research
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
The influence of study results on the chances of publication and the tendency of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Publication bias has an impact on the interpretation of clinical trials and meta-analyses. Bias can be minimized by insistence by editors on high-quality research, thorough literature reviews, acknowledgement of conflicts of interest, modification of peer review practices, etc.
Head and Neck Neoplasms
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)