What purpose is the DDMoRe library serving? · 2017. 9. 2. · anti-infectives , safety, and others...
Transcript of What purpose is the DDMoRe library serving? · 2017. 9. 2. · anti-infectives , safety, and others...
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On behalf of the DDMoRe consortium
What purpose is the DDMoRe library serving?
WCoP 2016 - Brisbane
Zinnia P Parra-Guillen and Iñaki F. Trocóniz
School of Pharmacy, University of Navarra, Pamplona, Spain
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•Background
•Intention & key features
•Structure
•Contents
•Functionalities
•Submission guidelines
Outline
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Current bottlenecks in applying efficiently MID3 include complexity of the structural and statistical sub-models, coding & dataset arrangement
• Drug and disease models available in literature are often difficult to re-implement
• To date no public-available drug and disease model libraries exist except for recent private initiatives
To fulfil part of the daily requirements in pharmacometrics an efficient repository needs to be far beyond a simple warehouse
Background
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Model library is one of the key products of DDMoRe
• It is an open, public-available and free-to-use cloud-based model library for drug and disease models
• Currently under development and which will be further supported by the DDMoRe foundation
DDMoRe model library provides a platform to:
(i) store and share models in a secure and version control manner,
(ii) friendly display key model features (e.g. structure, parameters)
(iii) annotate models based on ontology standards and metadata
(iv) connect to external databases
Intention & key features
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Structure and Functionalities (overview)
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Private Instance Public instance
No login restrictions Search for different public models Model & Language exploration Download
Login account Model submission Share and store own models Tracking of different versions
Model publication
Certification
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Contents
Items Description
Models Published models mainly in diabetes, oncology, other diseases as CNS and anti-infectives , safety, and others
Files Minimal requirements, automatically checked when submitting a model • Executable model code • Example of real or dummy dataset guiding data organization • Command text file illustrating how to execute the model • Set of annotations describing the modelling exercise and context of use • Output files (if the model is executable)
Language MDL and PharmML, the two standard languages developed by the DDMoRe consortium to enable interoperability Models provided in original target code
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78 models available*
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* Most of the current models have been published in peer review journals
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Functionalities overview
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Functionality Description
Access http://repository.ddmore.eu/
Browsing/Searching • Fully searchable engine reinforced by the used of metadata
• Relies on submitter provided information
Model exploration Optimal display when PharmML is used Access to version history Download
Connection to other DDMoRe products
Possibility to execute the model on different softwares
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An example
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An example
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Model annotation
Ensures that a relevant description of every model is collected
Enables queries for models based on key model features
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Free text
Metadata
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Overview (I)
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Overview (II)
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Model definition
Plus: • Initial conditions • Variability model • Covariate model • Observational model
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Estimation Steps
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Mandatory files
• Executable_Mielosupression.xml
Additional files
• Output_simulated_SEE_NONMEM.lst
• Neutrophils_VPC.tiff
• Simulated_WBC_plac_ddmore.csv
• Model_Accomodation.txt
• Neutrophils time profiles.tiff
• Executable_Mielosupression.mdl
• Command.txt
• Output_simulated_SSE_Monolix.txt
Files
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Mandatory files
• Executable_Mielosupression.xml
Additional files
• Output_simulated_SEE_NONMEM.lst
• Neutrophils_VPC.tiff
• Simulated_WBC_plac_ddmore.csv
• Model_Accomodation.txt
• Neutrophils time profiles.tiff
• Executable_Mielosupression.mdl
• Command.txt
• Output_simulated_SSE_Monolix.txt
Files
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Mandatory files
• Executable_Mielosupression.xml
Additional files
• Output_simulated_SEE_NONMEM.lst
• Neutrophils_VPC.tiff
• Simulated_WBC_plac_ddmore.csv
• Model_Accomodation.txt
• Neutrophils time profiles.tiff
• Executable_Mielosupression.mdl
• Command.txt
• Output_simulated_SSE_Monolix.txt
Files
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Mandatory files
• Executable_Mielosupression.xml
Additional files
• Output_simulated_SEE_NONMEM.lst
• Neutrophils_VPC.tiff
• Simulated_WBC_plac_ddmore.csv
• Model_Accomodation.txt
• Neutrophils time profiles.tiff
• Executable_Mielosupression.mdl
• Command.txt
• Output_simulated_SSE_Monolix.txt
Files
Reproduce results using the DDMoRe Interoperability Framework
Dataset example
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History
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Not all models have associated the PharmML code
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Not all models have associated the PharmML code
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Private model entry Default instance for any model uploaded, visible to submitter and those who he/she shared the model to. Need a repository account.
Public instance of model repository Transfer of model to public Instance upon user request (via "Publish" button) For models fulfilling minimal requirements only. Visible to anyone. No need for a repository account.
Private instance
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Submitter
Submitter
Upload/submit
Publish Required files
with description
Required files with
description
Annotations
Required files with
description
Annotations
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Submission Guidelines
Ground submission rules
• Quality depends solely on submitters
• Any models can be shared if fulfilling minimal requirements
• Discrepancy from publication needs to be documented
• Simulated data are needed to understand data structure and execute the models
• Output files are needed to check the model is executable and uncertainty on parameters
Terms of agreement
• Any submission is linked to a submitter name
• By publishing the submitter accepts to share model in the public domain
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Minimal requirements to publish
Technical: submitter provides relevant information for the scenario chosen
• Model code (MDL/PharmML or original) with description
• Dataset with description
• Output files with description
• Additional files like command for code execution
• Model annotation (e.g. author, disease area, context of use, ...)
Scientific: No requirements per se
• DDMoRe relies on the scientific community to fill the repository with relevant content
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Take home message (1/2)
Value How DDMoRe delivered this
Shared knowledge The repository holds (n>70) a diversity of simple and complex searchable models covering e.g. oncology, diabetes, CNS, infectious disease and safety
Scientific quality
Models are published based on annotation standards
Controlled environment Secure and sustained access to models. Standardized submission process.
Visibility DDMoRe repository content directly readable without login / easily found in google
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http://www.ddmore.eu/tutorial/tutorials-model-repository
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Take home message (2/2) It has been funded by EU for the world-wide modeling
community….
…. we can all benefit from the DDMoRe repository only if we continuously fill it with relevant models ….
(think about all the models you published, can you share at least one every 5 years? How difficult would that be?)
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Stephan Benay, Mihai Glont, Celine Sarr, Zinnia Parra-Guillén, Siv Jönsson
Modelling review group
WP1 participants
DDMoRe consortium
Acknowledgments
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Back-up slides
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Submission Guidelines
Four different scenarios to identify
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Private model entry Model in public domain
Model certification concept
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Submitter
Submitter
Upload/submit
Publish
Submitter
Required files with
description
Required files with
description
Annotations
Required files with
description
Annotations
Required files with
description
Annotations
DDMoRe Certification
Certification request
MRG1) Review
1) Modeling review group
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On behalf of the DDMoRe consortium
Annotate the
model
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