Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines

Eramet将以药物开发问题为中心，为开发者和监管机构制定儿科和孤儿药物的决策提供一种综合方法。这将构成一个透明的药物开发和评估生态系统，将促进采用建模和模拟(M&S)方法和相关数据类型(包括注册表和电子医疗保健数据等真实数据)。ERAMET的总体目标是提供和实施一个框架，以建立M&S方法和相关结果的可信度，作为监管程序内的证据来源。Eramet提出的生态系统将基于三大支柱：(1)连接问题、数据和方法的存储库。(2)制定和验证高质量的数据和分析方法标准(包括M&S方法和混合方法)。这些将涵盖计算M&S、数字双胞胎、人工智能、混合方法、标准统计学和药物计量学，作为分析方法和替代数据类型和来源，如RWD、电子健康数据、注册、历史监管提交、科学和(非)临床试验。(3)一个基于人工智能的平台，将自动化和优化数据收集、格式化和建模以及模拟分析，并实施可信度评估。作为Eramet的一部分，该生态系统将应用于五个使用案例，包括儿科推断和4组罕见疾病的药物益处/风险特征，即共济失调、输血依赖型血红蛋白病、支气管肺发育不良和退行性神经肌肉疾病。每个用例都计划通过EMA鉴定程序提交和监管部门批准至少一个经过验证的M&S工具。将提议进行培训，以使监管评估员、药物开发商和临床研究人员熟悉这一新方法。

ERAMET will provide an integrated approach for developers and regulators’ decision-making for paediatric and orphan drugs, centred on the drug development questions. This will constitute a transparent ecosystem for drug development and assessment, that will facilitate the adoption of modelling and simulation (M&S) methods and related data types (including real word data such as registries and electronic healthcare data). The overall objective of ERAMET is to provide and implement a framework for establishing the credibility of M&S methods and related results as sources of evidence within regulatory procedures. The ecosystem proposed by ERAMET will be based on three pillars: (1) A repository connecting questions, data and methods. (2) The development and validation of high-quality standards for data and analytical methods (including M&S and hybrid approaches). These will cover computational M&S, digital twins, AI, hybrid approaches, standard statistics and pharmacometrics, as analytical methods and alternative data types and sources such as RWD, eHealth data, registries, historical regulatory submissions, scientific and (non)clinical trials). (3) An AI-based platform that will automate and optimise the data collection, formatting and modelling and simulation analysis and implement the credibility assessment. As part of ERAMET, the ecosystem will be applied to five use-cases including paediatric extrapolation and characterisation of drug benefit/risk in 4 groups of rare diseases, namely ataxia, transfusion dependent haemoglobinopathies, bronchopulmonary dysplasia, and degenerative neuromuscular. Each of the use-case is planned to lead to submission and regulatory approval of at least one validated M&S tool via the EMA qualification procedure. Training will be proposed to familiarise regulatory assessors, drug developers and clinical researchers with this new approach.