Toward Good Simulation Practice. Best Practices for the Use of Computational Modelling and Simulation in the Regulatory Process of Biomedical Products

✍ Scribed by Marco Viceconti, Luca Emili

• Publisher: Springer
• Year: 2024
• Tongue: English
• Leaves: 153
• Series: Synthesis Lectures on Biomedical Engineering
• Category: Library

✦ Table of Contents

Foreword
FDA Perspective on Modeling and Simulation and the Need for Good Simulation Practice
Acknowledgements
Contents
1 Introduction
1.1 Scope of this Document
1.2 The Critical Elements of a Good Simulation Practice Standard
1.2.1 Theoretical Foundations of Good Simulation Practice
1.2.2 Model Development
1.2.3 Model Credibility
1.2.4 Possible Regulatory Pathways
1.2.5 Possible Health Technology Assessment Pathways
1.2.6 Ethical Review of In Silico Methodologies
1.2.7 The Role of the Sponsor in In Silico Methodologies
1.2.8 The Role of the Investigator in In Silico Methodologies
1.3 Essential Good Simulation Practice Recommendations
References
2 Theoretical Foundations of Good Simulation Practice
2.1 Introduction
2.2 What is a Model in Science?
2.3 A Short Reflection on the Theoretical Limits of Models and Experiments
2.4 Model for Hypothesis Testing, Models for Problem-Solving
2.5 Assessing the Degree of Analogy of a Model: Evidence by Induction
2.6 The Theoretical Framing of VVUQ
2.7 Levels of Credibility Testing
2.8 The Conundrum of Validating Data-Driven Models
2.9 Conclusions
2.10 Essential Good Simulation Practice Recommendations
References
3 Model Development
3.1 A Risk-Based Paradigm of Model Development as a Function of Its Context of Use
3.2 SLC Industry Standards and Relevance for Model Development
3.2.1 Analysis and Requirements
3.2.2 Design
3.2.3 Implementation and Integration
3.2.4 Testing
3.2.5 Maintenance
3.3 Conclusions
3.4 Essential Good Simulation Practice Recommendations
References
4 Model Credibility
4.1 Introduction
4.2 Model Credibility in Existing Regulatory Guidelines
4.3 A Standard Framework: ASME VV-40:2018
4.4 Verification
4.4.1 Code Verification
4.4.2 Calculation Verification
4.5 Validation
4.5.1 A General Definition
4.5.2 Definition and Examples
4.5.3 Validation Layers for in Silico Methodologies
4.5.4 Uncertainty Quantification
4.6 Applicability of the Validation Activities
4.7 VVUQ Considerations for Data-Driven Models and Agent-Based Models
4.8 Final Credibility
4.9 Essential Good Simulation Practice Recommendations
References
5 Possible Qualification Pathways for In Silico Methodologies
5.1 Introduction
5.2 Pre-certification as Predictive SaMD
5.3 Certification of the Technical Validity
5.4 Towards an Ad Hoc Qualification Pathway for In Silico Methodologies
5.5 Adapting the Existing Qualification Pathways to In Silico Methodologies
5.6 Essential Good Simulation Practice Recommendations
References
6 Possible Health Technology Assessment Pathways
6.1 Introduction
6.2 Assessing in Silico Methodologies for HTA
6.3 Introduction to Health Technology Assessment (HTA)
6.4 In Silico Methodologies as a Source of Evidence
6.4.1 Medical Devices and Interventions
6.4.2 Pharmaceutical Products
6.5 In Silico Methodologies: Product Life Cycle and HTA
6.6 Methodologies for in Silico Clinical Studies
6.6.1 HTA Health Technology Assessment
6.6.2 Discovery, Design and Pre-clinical Stages
6.6.3 Clinical Development
6.6.4 Market Access and Post-marketing Assessment
6.6.5 Post-marketing Assessment
6.7 Critical Assessment of the in Silico Approach and Limitations
6.8 How to Assess Evidence from in Silico Methodologies?
6.9 Challenges for the Future
6.10 Definitions of Various HTA Modalities
6.11 Essential Good Simulation Practice Recommendations
References
7 Ethical Review of In Silico Methodologies
7.1 Introduction
7.2 Short Overview of Ethical Review in Clinical Trials
7.3 The Ethical Benefits of In Silico Methodologies
7.3.1 Refinement
7.3.2 Reduction
7.3.3 Replacement
7.4 The Ethical Review of Studies Involving In Silico Methodologies
7.5 Data Protection
7.6 Credibility Assessment in the IEC/IRB Review
7.7 Essential Good Simulation Practice Recommendations
References
8 The Sponsor
8.1 Introduction
8.2 Relevant Expertise
8.3 Quality Management, Quality Assurance and Quality Control
8.3.1 Risk Identification, Evaluation, Control, Communication, Review, and Reporting
8.3.2 Standard Operating Procedures
8.4 Contract Research Organisation (CRO)
8.4.1 Relevant Expertise
8.4.2 Allocation of Roles and Responsibilities
8.5 Adoption of Computer Simulations in the Definition of the Global Development Plan
8.5.1 Pre-clinical Development Plan
8.5.2 Clinical Development Plan
8.6 Investigator Selection
8.6.1 General Requirements
8.6.2 Investigational Centre Selection
8.7 Study Design, Setup, and Management
8.8 Data Handling and Record Keeping
8.9 Compliant GxP Computerised Systems
8.10 Monitoring Procedures
8.11 Audit
8.12 Non-compliance
8.13 Premature Termination or Suspension of a Trial
8.14 Trial/study Reports
8.15 Essential Good Simulation Practice Recommendations
9 The Investigator: Modellers and Analysts
9.1 Roles and Responsibilities
9.2 Investigator's Brochure
9.3 Investigator's Qualifications
9.4 Adequate Resources
9.5 Records and Reports
9.6 Safety and Security
9.7 Essential Good Simulation Practice Recommendations
References
Annex: A Review of the Existing Regulatory Guidance on the Use of Computational Models
Glossary