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Project: DDMoRe
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Document name: Glossary
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GlossaryWork Package 8: Documentation
Author: Jonathan ChardPrepared by: Wendy Aartsen, Eva Potters
Approved by:
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Table of contents
1 Definitions........................................................................................................31.1 Acronyms and Abbreviations...................................................................31.2 Definitions and System Names................................................................3
2 Document Revision History...............................................................................3
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1 Definitions1.1 Acronyms and AbbreviationsAcronym Definition
21 CFR Part 11 21 Code of Federal Regulations (21 CFR Part 11) Electronic Records; Electronic Signatures
AE Adverse Event
AIC Akaike Information Criterion
AMT Amount of dose at a specified time
AoI Area of Interest
APE Absolute Prediction Error
API Application Programmers Interface
Interface exposed to a programming language to allow tools to be accessible to other software
ASCII American Standard Code for Information Interchange
BBB Blood Brain Barrier
BIC Bayesian Information Criterion
BQL Below quantifiable limit
BURNIN Number of MCMC iterations to discard before sampling for inference (MCMC method)
CI Confidence Interval
CLI Command Line Interface
CNS Central Nervous System
Connector A piece of software which enables modelling software to communicate with the interoperability framework
CRD Completely Random Dropout
CRM Continuous Reassessment Method
CSDISC Clinical Data Interchange Standards Consortium
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CSV i] Comma separated valuesii] Computerized system validation
CTS Clinical Trial Simulation
DAE Differential-Algebraic Equation
DDE Delay Differential Equation
DDMoRe Drug Disease Model Resources
DMR Data and Modelling ResourceArtefacts used throughout the modelling process, such as datasets, model definitions, and results.
DMX Drug Model Explorer (see Names)
D-opt/G-opt D-optimality / G-optimality (optimal design metric)
DoW Description of Work
DV Dependent Variable
EFPIA European Federation of Pharmaceutical Industries and Associations
EMEA European Medicines Agency
F2F Face-to-Face
FDA Food and Drug Administration
FIM Fisher Information Matrix (optimal design metric)
FO First Order
FOCE First Order (Conditional Estimation)
FOCEI First Order (Conditional Estimation) with Interaction
GLM General Linear Model
GUI Graphical User Interface
IDV Independent Variable
IMI Innovative Medicines Initiative
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IMI-JU Innovative Medicines Initiative Joint Undertaking
IQ Installation Qualification (see Definitions)
ITER Number of iterations (MCMC or NONMEM control)
JVM Java Virtual Machine
LAN Local Area Network
LLOQ Lower Limit of Quantification
M&S Modelling and Simulation
MAXEVAL Maximum Evaluations
MCL Model Coding LanguageThe MCL is a declarative language used to define the mathematical structure of the model
MCMC Markov Chain Monte Carlo
MCPEM Monte Carlo Parametric Expectation Maximization
MDL Modelling Definition LanguageThe modelling definition is comprised of two parts, the MCL and the TEL.
MDV Missing dependent variable
MML Modelling Markup LanguageThe Modelling Markup Language is a machine-readable representation of the data and modelling resources created and stored in a project
MSE Mean Squared Error
MTD Maximum Tolerated Dose
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NAS Network Attached Storage
NDLM Normal Dynamic Linear Model
NFS Network File System
NLMEM A new SAS/IML macro for hierarchical nonlinear models.
NONMEM NONLinear Mixed Effects Modelling (see Names)
NPC Numerical Predictive Check
ODE Ordinary Differential Equation
OFV Objective Function Value (NONMEM output)
OPTDES Optimal Design
OQ Operational Qualification (see Definitions)
PBPK Physiologically based pharmacokinetic(s)
PD Pharmacodynamic(s)
PDE Partial Differential Equation
PDF Portable Document Format
PE Prediction Error
PFIM Population Fisher Information Matrix
PI Prediction Interval
PK Pharmacokinetic(s)
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PKBUGS Bayesian Inference Using Gibbs Sampling (PharmacoKinetics) (see Names)
PKS Pharsight Knowledgebase Server (see Names)
PPC Posterior Predictive Check
PQ Performance Qualification (see Definitions)
PsN Perl Speaks NONMEM (modelling software for managing NONMEM runs)
QQ (plot) Quantile-Quantile plot
R R (see Names)
RCP Rich Client Platform
RD Random Dropout
RSE Relative Standard Error
RTF Rich Text FormatAn open document format supported by Word
SAEM Stochastic Approximation Expectation Maximization
SAS Statistical Analysis System (see Names)
SB System biology
scp Secure Copy
SD or Stdev Standard Deviation
SDE Stochastic Differential Equation
SDTM Study Data Tabulation Model
SE Standard Error
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sftp SSH File Transfer Protocol
SGE Sun Grid Engine
SIG Significant digits (NONMEM control statement)
SLURM Simple Linux Utility for Resource Management
SMP Symmetric Multiprocessing
SSH Secure Shell
SPE Standardized Prediction Error
SWT Standard Widget Toolkit
TEL Task Execution LanguageThe TEL is an imperative language that describes a sequence of task that perform some actions on the model described with the MCL
TC Teleconference
VPC Visual Predictive Check
WAN Wide Area Network
WP Work Package
WSDL Web Service Definition Language
XML eXtensible Markup Language
- (dash) Indicates lack of response/data
1.2 Definitions and System NamesSystem Name Description
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21 CFR Part 11 FDA rule that defines parameters by which pharmaceutical companies can author, approve, store, and distribute records electronically.http://www.f d a.gov/ o ra/c om pliance _ ref / part11/
Actor In the context of software requirements analysis this is the role adopted by a person or system when interacting with a software system.
AdaptiveRandom Search
Adaptive Random Search is a search technique in which the parameter space is investigated by drawing from a vector with large variances when far away from the global optimum, and when in the region of the global optimum, to reduce the variance by giving more detailed investigation.
Administrator A specific user role with privileges to manage users, job queues, system access, etc.
AnalysisDataset
A dataset (derived from an Import Dataset), which can be used for model estimation.
BayesianInference
Bayesian Inference is statistical inference in which prior evidence or observations are used to update or to newly infer the probability that a hypothesis may be true.
Berkeley Madonna
Berkeley Madonna is a general-purpose differential equation solver and real-time simulation tool. http://www.berkeleymadonna.com
CDISC A suite of global, platform independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.
Central Integrated Database
A database within the system that holds all relevant information (Import Datasets, Analysis Datasets, model definitions, model output, scripts, etc).
Citrix Citrix A suite of remote application delivery software developed by Citrix. http://www.citrix.com/
Comma- Separated Values (CSV)
Comma-Separated Values (also known as a comma-separated list) is a file format that stores tabular data as ASCII separated by commas.
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Computerized System Validation(CSV2)
The documented process of assuring that a computerized system does exactly what it is designed to do in a consistent and reproducible manner.
Data The term data refers to qualitative or quantitative attributes of a variable or set of variables. Data (plural of "datum") are typically the results of measurements and can be the basis of graphs, images, or observations of a set of variables.
Data are often viewed as the lowest level of abstraction from which information and then knowledge are derived.
Raw data, i.e. unprocessed data, refers to a collection of numbers, characters, images or other outputs from devices that collect information to convert physical quantities into symbols.
Data Views Different formats for viewing data (e.g. spreadsheet format, etc).
Dataset A data set (or dataset) is a collection of data, usually presented in tabular form. Each column represents a particular variable.
Each row corresponds to a given member of the data set in question. Its values for each of the variables, such as height and weight of an object or values of random numbers. Each value is known as a datum.
The data set may comprise data for one or more members, corresponding to the number of rows.
Design The general framework for a randomized controlled experiment used to investigate a particular drug effect, including exposure-disease relationships.
DistributedComputing
The distribution of computational workload between several computers in a cluster or grid.
DMX Drug Model Explorer –a program for exploring drug characteristics based on modelling and simulation results. http://www.pharsight.com/products/prod_dmx_home.php
D-optimality Optimality criterion based on the maximization of the determinant of the Fisher information matrix (max det F), or, equivalently, minimizing the determinant of its inverse.
Eclipse RCP A platform for building and deploying rich client applications.
ED-optimality Optimality criterion based on the maximization of the expected value (over a given parameter distribution) of the determinant of Fisher
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information matrix.
ElectronicSignatures
Food and Drug Administration 21 CFR Sec. 11.3 definitions: Electronic signature means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual’s handwritten signature.http://www. ac c e s s data.fda . gov / s c ripts / c dr h/cfd oc s /c f c fr/C F RSe a r c h.cf m ? fr=11. 10 0
End-User A specific user role with privileges to manage only his/her own jobs queues, etc.
Estimation A mathematical or statistical procedure for the derivation of model parameters, given a specific set of data.
Extensible Markup Language (XML)
An open standard for exchanging structured documents and data over the Internet that was introduced by the World Wide Web Consortium (W3C).
ExternalAuthentication
The process of using the operating system to authenticate users to an application. External authentication eliminates the need for users to log in to both the operating system and the application.
Feature A description of some functionality that will be part of the implemented system.
FederovExchange
This is an iterative algorithm that replaces at each iteration a design point with the point from a list of candidate points that improve the design most. To increase the probability of finding the global optimum, several tries are made using different starting designs.
Git A distributed version control system.
Hyper- threading
Hyper-threading technology allows a single processor to run two threads at the same time.
Import Data FileStructure
A common structure of data files that can be imported into the system.
Import Dataset
A set of raw data imported into the system.
Input Data FileTypes
Types of files that can be used when importing data.Input data file types must include (but need not be limited to) the following: ASCII, Excel, SAS, S-plus, NONMEM (data file), SDTM (CDISC), PKS.
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Installation Qualification (IQ)
A product setup qualification which checks that the correct items have been installed, that the site requirements for the system have been met, and that the system is functional.
Job SchedulingManagement
Functionality to manage job queues, and at any time prioritise, kill, suspend, and restart jobs.
Kerberos Kerberos is the name of a computer network authentication protocol, which allows individuals communicating over an insecure network to prove their identity to one another in a secure manner, and also a suite of free software published by Massachusetts Institute of Technology (MIT) which implements this protocol.
LaTeX A high quality typesetting system that includes features designed for the production of technical and scientific documentation.
MATLAB MATLAB is a commercial “Matrix Laboratory”, which operates as an interactive programming environment. http://www.mathworks.com/products/matlab
Metadata Metadata (metacontent) is defined as data providing information about one or more aspects of the data, such as:
Means of creation of the data Purpose of the data
Time and date of creation
Creator or author of data
Placement on a computer network where the data was created
Standards used
Methods ofEstimation
Numerical algorithms for solving nonlinear mixed-effects problems.The Methods of Estimation supported by the system must include: FO, FOI, FOCE, FOCEI, LAPLACIAN, Lindstrom and Bates, MCMC (based methods), MCPEM, SAEM, Gaussian Quadrature, and nonparametric methods.
Model A mathematical description of the behaviour of a system.
Module An independent component of the system designed to facilitate a specific task.
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Monte CarloSimulation
An analytical technique in which a large number of simulations are run using random quantities for uncertain variables, and looking at the distribution of results to infer which values are most likely.
Multitasking The ability to run more than one task or program at the same time. In the case of this application it refers to batch jobs (causing no application locks) and multiple user sessions (concurrently on one desktop) to modify and run jobs at the same time.
NM-TRAN The language used to define models that are executed with NONMEM.
NONMEM NONMEM is the gold standard software for nonlinear mixed-effects modelling. http://www.globomax.com/nonmem.htm
NumericalPrecision
Property of a numerical algorithm describing the precision with which results can be produced.
NumericalStability
Property of a numerical algorithm describing its ability to run without causing exceptions, its ability to converge, and reproducibility of its results.
Operational Qualification (OQ)
Tests to determine that the system performs against a specification in terms of functional tests performed on individual components of the system.
Oracle Oracle Corporation is one of the major companies developing database management systems (DBMS). http://www.oracle.com
Other Diseases area
Therapeutic areas different from diabetes and oncology
Output DataFile Types
Types of files that can be used when exporting data.Output data file types must include (but need not be limited to) the following: ASCII, Excel, SAS, S-plus, NONMEM (data file), SDTM (CDISC), Word (for reports), MATLAB, R, PKS.
Performance Qualification (PQ)
Tests to verify that the systems and equipment, as connected together in the target environment, can perform effectively and reproducibly.
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Pirana Work on a cluster, or locally. Use the PsN-toolkit for advanced M&S. Uses R and Xpose to create plots
http://www.pirana-software.com/
PKBUGS Add-on package for WinBUGS dealing with the analysis of pharmacokinetic data. http://www.mrc-bsu.cam.ac.uk/bugs/winbugs/pkbugs.shtml
PKS Pharsight Knowledgebase Server – is a database system for managing PK/PD data. http://www.pharsight.com/products/prod_pks_home.php
PopDes A program for Optimal Design of univariate and multivariate, Individual and Population Pharmacokinetic and Pharmacodynamic Experiment running under Matlab. mailto:[email protected]
Power The power of a statistical test is the probability that the test will reject a false null hypothesis, or in other words that it will not make a Type II error. As power increases, the chances of a Type II error decrease, and vice versa.
Project A project is classed as a single piece of work in which a user has a specific “question to answer” or a hypothesis to test.
R R is a tool for statistical analysis and generation of graphs. http://www.r-project.org
Relational Database Technologies
Database technology based on the relational model for database management, which is a data model based on predicate logic and set theory.
Result Set A result set is generated by the execution of a task specified in the task execution language. A result set could be:
- A dataset (generated by some manipulation of an existing dataset, or generated using some simulation)
- A parameter estimation- A model simulation- Post-analysis on the outputs of a parameter estimation
Reviewer A specific user role with read-only privileges.
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Risk Analysis A qualitative technique which involves a disciplined analysis of the events which could transform a potential hazard into undesired outcomes.
Sample Size Sample Size, usually designated ”n,” is the number of individuals or repeated measurements in an experiment.
SAS SAS is a comprehensive system for performing e.g. statistical analysis. http://www.sas.com
SDTM
Simplex The simplex method (or Nelder-Mead or downhill simplex method) is a commonly- used nonlinear optimization algorithm for minimizing an objective function in amulti-dimensional space.
SimulatedAnnealing
An algorithm for solving “hard” problems (insoluble through numerical methods), notably combinatorial optimization, based on the metaphor of annealing.
Simulation A mathematical or statistical procedure for the generation of hypothetical data given a specific model and study design.
S-PLUS S-PLUS is a general purpose statistics package using the S programming language. http://www.insightful.com/products/splus/default.asp
Step A step in a project is composed of a set of working files, in particular:- Zero, one or many datasets- A model written in the MCL- Zero, one or many tasks written in the TEL- Zero, one or many result sets generated as a result of the
execution of a task written in the TEL
Summary LevelPredictions
Synthesis of a simulation outcome, presented graphically or numerically.
Symmetric Multiprocessing (SMP)
The distribution of computational workload between separate processors that share the same physical memory.
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System A group, set, or aggregate of things, natural or artificial, forming a connected or complex whole.
SystemStability
The ability of a computer system to function appropriately with a given (high) workload, e.g. with a given number of concurrent users running a given number of simultaneous jobs.
Task
Term Description
TRELLIS TRELLIS is a powerful graphical toolkit used to display relationships in large datasets compactly within a single display, using panels to distinguish between different groups.
Type I Error Also known as an "error of the first kind", an α error, or a "false positive": the error of rejecting a null hypothesis when it is true.
Type II Error Also known as an "error of the second kind", a β error, or a "false negative": the error of not rejecting a null hypothesis when the alternative hypothesis is true.
Use case A set of scenarios describing how the System will respond its environment; typically user interaction or interactions with other software systems.
User Roles The different roles that users may undertake, e.g. administrator/end-user/reviewer. Each user role has different privileges in terms of the User Tasks he/she is allowed to perform.
User Tasks The actions possible within the system, e.g. in terms of management of job queues.
Variance- covariance Matrix
The Variance-covariance Matrix is a matrix of covariances between elements of a vector of model parameter estimates given a model and design, the diagonals of which are variances.
WinBUGS Windows implementation of the BUGS (Bayesian Inference Using Gibbs Sampling) project, concerned with flexible software for the Bayesian analysis of complex statistical models using Markov chain Monte Carlo (MCMC) methods. http://www.mrc-bsu.cam.ac.uk/bugs/winbugs/contents.shtml
Windows Active Active Directory is an implementation of LDAP directory services by
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DirectoryServer
Microsoft for use in Windows environments.
WinPOPT WinPOPT and POPT are a set of programs written in MATLAB that can be used for optimization of nonlinear mixed effects models. http://www.winpopt.com
Workflow The tasks, procedural steps, and organization, given the required input and output information, needed for each step of a data analysis process.
Xpose Xpose is an R-based model building aid for population analysis using NONMEM. http://xpose.sourceforge.net/
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2 Document Revision History
Version Author Date Description0.1 J Chard 22/8/2011 Initial version0.2 J Chard 30/9/2011 Incorporated glossary items
added to the prototype and requirements document
0.3 W. Aartsen 23/12/2011 Incorporated glossary items from MCL specification
0.4 W. Aartsen 16/07/2012 Incorporated glossary items from MCL and TEL specification draft 3, documentation on the API
0.5 W. Aartsen 17/12/2012 Incorporated glossary items from D8.59 Documentation of existing tools
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