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In Silico Clinical Trials
An ''in silico'' clinical trial, also known as a virtual clinical trial, is an individualized computer simulation used in the development or regulatory evaluation of a medicinal product, device, or intervention. While completely simulated clinical trials are not feasible with current technology and understanding of biology, its development would be expected to have major benefits over current ''in vivo'' clinical trials, and research on it is being pursued. History The term ''in silico'' indicates any use of computers in clinical trials, even if limited to management of clinical information in a database. Rationale The traditional model for the development of medical treatments and devices begins with pre-clinical development. In laboratories, test-tube and other ''in vitro'' experiments establish the plausibility for the efficacy of the treatment. Then ''in vivo'' animal models, with different species, provide guidance on the efficacy and safety of the product for humans. Wi ...
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Computer Simulation
Computer simulation is the process of mathematical modelling, performed on a computer, which is designed to predict the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be determined by comparing their results to the real-world outcomes they aim to predict. Computer simulations have become a useful tool for the mathematical modeling of many natural systems in physics (computational physics), astrophysics, climatology, chemistry, biology and manufacturing, as well as human systems in economics, psychology, social science, health care and engineering. Simulation of a system is represented as the running of the system's model. It can be used to explore and gain new insights into new technology and to estimate the performance of systems too complex for analytical solutions. Computer simulations are realized by running computer programs that can be either small, running almost instantly on small devices, or large ...
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Covariate
Dependent and independent variables are variables in mathematical modeling, statistical modeling and experimental sciences. Dependent variables receive this name because, in an experiment, their values are studied under the supposition or demand that they depend, by some law or rule (e.g., by a mathematical function), on the values of other variables. Independent variables, in turn, are not seen as depending on any other variable in the scope of the experiment in question. In this sense, some common independent variables are time, space, density, mass, fluid flow rate, and previous values of some observed value of interest (e.g. human population size) to predict future values (the dependent variable). Of the two, it is always the dependent variable whose variation is being studied, by altering inputs, also known as regressors in a statistical context. In an experiment, any variable that can be attributed a value without attributing a value to any other variable is called an ind ...
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Computational Science
Computational science, also known as scientific computing or scientific computation (SC), is a field in mathematics that uses advanced computing capabilities to understand and solve complex problems. It is an area of science that spans many disciplines, but at its core, it involves the development of models and simulations to understand natural systems. * Algorithms ( numerical and non-numerical): mathematical models, computational models, and computer simulations developed to solve science (e.g., biological, physical, and social), engineering, and humanities problems * Computer hardware that develops and optimizes the advanced system hardware, firmware, networking, and data management components needed to solve computationally demanding problems * The computing infrastructure that supports both the science and engineering problem solving and the developmental computer and information science In practical use, it is typically the application of computer simulation and other fo ...
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Medical Technology
Health technology is defined by the World Health Organization as the "application of organized knowledge and skills in the form of devices, medicines, vaccines, procedures, and systems developed to solve a health problem and improve quality of lives". This includes pharmaceuticals, devices, procedures, and organizational systems used in the healthcare industry, as well as computer-supported information systems. In the United States, these technologies involve standardized physical objects, as well as traditional and designed social means and methods to treat or care for patients. Development Pre-digital Era During a pre-digital era, patients suffered from inefficient and faulty clinical systems, processes, and conditions. Many medical errors happened in the past due to undeveloped health technologies. Some examples of these medical errors included adverse drug events and alarm fatigue. Alarm fatigue is caused when an alarm is repeatedly triggered or activated and one becomes d ...
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Virtual Screening
Virtual screening (VS) is a computational technique used in drug discovery to search libraries of small molecules in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor or enzyme. Virtual screening has been defined as "automatically evaluating very large libraries of compounds" using computer programs. As this definition suggests, VS has largely been a numbers game focusing on how the enormous chemical space of over 1060 conceivable compounds can be filtered to a manageable number that can be synthesized, purchased, and tested. Although searching the entire chemical universe may be a theoretically interesting problem, more practical VS scenarios focus on designing and optimizing targeted combinatorial libraries and enriching libraries of available compounds from in-house compound repositories or vendor offerings. As the accuracy of the method has increased, virtual screening has become an integral part of the drug discove ...
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Virtual Physiological Human
The Virtual Physiological Human (VPH) is a European initiative that focuses on a methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system. The collective framework will make it possible to share resources and observations formed by institutions and organizations, creating disparate but integrated computer models of the mechanical, physical and biochemical functions of a living human body. VPH is a framework which aims to be descriptive, integrative and predictive.STEP research road map
Clapworthy ''et al.'' state that the framework should be descriptive by allowing laboratory and healthcare observations around the world "to be collected, catalogued, organized, shared and combined in any possible way." It shou ...
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In Silico Medicine
''In silico'' medicine (also known as "computational medicine") is the application of '' in silico'' research to problems involving health and medicine. It is the direct use of computer simulation in the diagnosis, treatment, or prevention of a disease. More specifically, ''in silico'' medicine is characterized by modeling, simulation, and visualization of biological and medical processes in computers with the goal of simulating real biological processes in a virtual environment. History The term ''in silico'' was first used in 1989 at a workshop "Cellular Automata: Theory and Applications" by a mathematician from National Autonomous University of Mexico (UNAM). The term ''in silico radiation oncology'', a precursor of generic ''in silico'' medicine was coined and first introduced by G. Stamatakos in Proceedings of the IEEE in 2002. The same researcher coined and introduced the more generic term ''in silico oncology''. ''In silico'' medicine is considered an extension of previou ...
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In Silico
In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases , , and , which are commonly used in biology (especially systems biology). The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature. History The earliest known use of the phrase was by Christopher Langton to describe artificial life, in the announcement of a workshop on that subject at the Center for Nonlinear Studies at the Los Alamos National Laboratory in 1987. The expression ''in silico'' was first used to characterize biological experiments carried out entirely in a computer in 1989, in the workshop "Cellular Automata: Theory and Applications" in Los Alamos, New Mexico, by Pedro Miramontes, a ma ...
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Generative Adversarial Network
A generative adversarial network (GAN) is a class of machine learning frameworks designed by Ian Goodfellow and his colleagues in June 2014. Two neural networks contest with each other in the form of a zero-sum game, where one agent's gain is another agent's loss. Given a training set, this technique learns to generate new data with the same statistics as the training set. For example, a GAN trained on photographs can generate new photographs that look at least superficially authentic to human observers, having many realistic characteristics. Though originally proposed as a form of generative model for unsupervised learning, GANs have also proved useful for semi-supervised learning, fully supervised learning, and reinforcement learning. The core idea of a GAN is based on the "indirect" training through the discriminator, another neural network that can tell how "realistic" the input seems, which itself is also being updated dynamically. This means that the generator is not trai ...
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Intention To Treat
In medicine an intention-to-treat (ITT) analysis of the results of a randomized controlled trial is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifacts that can arise in intervention research such as non-random attrition of participants from the study or crossover. ITT is also simpler than other forms of study design and analysis, because it does not require observation of compliance status for units assigned to different treatments or incorporation of compliance into the analysis. Although ITT analysis is widely employed in published clinical trials, it can be incorrectly described and there are some issues with its application. Furthermore, there is no consensus on how to carry out an ITT analysis in the presence of missing outcome data. Rationale Randomized clinical trials analyzed by the intention-to-treat (ITT) approach provide unbiased comparisons among the treatment groups. In ...
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Compliance (medicine)
In medicine, patient compliance (also adherence, capacitance) describes the degree to which a patient correctly follows medical advice. Most commonly, it refers to medication or drug compliance, but it can also apply to other situations such as medical device use, self care, self-directed exercises, or therapy sessions. Both patient and health-care provider affect compliance, and a positive physician-patient relationship is the most important factor in improving compliance. Access to care plays a role in patient adherence, whereby greater wait times to access care contributing to greater absenteeism. The cost of prescription medication also plays a major role. Compliance can be confused with concordance, which is the process by which a patient and clinician make decisions together about treatment. Worldwide, non-compliance is a major obstacle to the effective delivery of health care. 2003 estimates from the World Health Organization indicated that only about 50% of patients with ...
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Central Tendency
In statistics, a central tendency (or measure of central tendency) is a central or typical value for a probability distribution.Weisberg H.F (1992) ''Central Tendency and Variability'', Sage University Paper Series on Quantitative Applications in the Social Sciences, p.2 Colloquially, measures of central tendency are often called ''averages.'' The term ''central tendency'' dates from the late 1920s. The most common measures of central tendency are the arithmetic mean, the median, and the mode. A middle tendency can be calculated for either a finite set of values or for a theoretical distribution, such as the normal distribution. Occasionally authors use central tendency to denote "the tendency of quantitative data to cluster around some central value."Upton, G.; Cook, I. (2008) ''Oxford Dictionary of Statistics'', OUP (entry for "central tendency")Dodge, Y. (2003) ''The Oxford Dictionary of Statistical Terms'', OUP for International Statistical Institute. (entry for "ce ...
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