Methodology

INVENTS aims to generate in silico (trials) based on existing knowledge and computational models under extrapolation approach and geometric distance approach

In 2013, the EU Commission funded three consortia under the call HEALTH.2013.4.2.3 – New methodologies for clinical trials for small population groups. These consortia focused on developing new methodologies for clinical trials in small population groups. While these consortia have published recommended methods, some applied in areas like neonatal seizures and Lyell Syndrome, recent revisions of EU legislation highlight underutilization of scientific and technological advancements. Nearly a decade later, as stated by the EU legislation on medicines for children and rare diseases initiative (EU Law 2021), there’s a recognized need for further development of methods and enhanced support for evaluating evidence from innovative approaches in clinical trials.

Overall methodology

INVENTS methodological development is based on 5 major methodological blocks, all complementary and interconnected. They are supported by 3 blocks including use cases, patients’ engagements and legal perspectives.

 

INVENTS WPs structure and relation between WPs

WP1

Increasing robustness of model-based treatment and extrapolation methods

WP2

Cope with missing knowledge

WP3

Increasing robustness of small population confirmatory trials

WP4

Proposing evidence synthesis approach

WP5

Developing evidence tools for regulatory decision making in RD

WP6

Ethical, legal issues and patients’ engagement in a regulatory perspective

WP7

Use cases and data sharing

WP8

Management and knowledge transfer

Identifying gaps in the knowledge-based workflow for in silico (trials)

Identifying gaps in the knowledge-based workflow for in silico (trials)

INVENTS framework for decision making

WP2

Cope with missing knowledge

 

Objectives:

To evaluate, to assess and to propose a workflow for using in silico methods, and approaches to generate virtual patients using various data sources and computational models

WP Leader

Main contributors

WP3

Increasing robustness of small population confirmatory trials 

 

Objectives:

To develop and assess innovative clinical trial designs that make use of mature computational models such as PKPD and in silico trials to improve the efficiency and robustness of these trials

WP Leader

Main contributors

WP4

Proposing evidence synthesis approach 

 

Objectives:

To deepen the understanding of how information originating from very different data sources should be synthesized, in particular, when in silico trials generating virtual patients and cohorts are involved. 

WP Leader

Main contributors

WP5

Developing evidence tools for regulatory decision making in RD

 

Objectives:

To provide applicants and assessors with a framework, assessment criteria and associated decision tools use of computational models with high impact on decision making for marketing approval and reimbursement for small populations. Models, spanning from fundamental to real-world data integration.

WP Leader

Main contributors

WP6

Ethical, legal issues and patients’ engagement in a regulatory perspective

 

Objectives:

To ensure the Ethical, Legal and Regulatory requirements and Patients’ perspective implementation

WP Leader

Main contributors

WP7

Use cases and data sharing

 

Objectives:

To provide use cases for the methods developed in work packages 1-5 and provide relevant data and disease area expertise. 

WP Leader

Main contributors

WP8

Management and knowledge transfer

 

Objectives:

To provide efficient management and coordination of the project and the consortium and to ensure progress of the project towards its planned objectives. To also address dissemination, communication and training activities as well as the protection, exploitation and further use of the project results

WP Leader

Main contributors

WP1

Increasing robustness of model-based treatment and extrapolation methods

 

Objectives:

To improve the robustness of extrapolation, modeling and simulation methods, to propose tools helping implement these approaches, and to provide evaluation criteria to use them in the decision-making process.

WP Leader

Main contributors