In Silico World D9.1 Legal and ethical inventory

Executive Summary:

The present Deliverable ‘D9.1 – Legal and Ethical Inventory’, part of Work Package 9 ‘Ethical and Legal Framework’ of the In Silico World project, provides an overview of the core pieces of legislation and ethical principles that are relevant to the In Silico project, and thus, in silico trials.

The analysis finds the following areas of legislation are of relevance:

• Privacy and Data Protection: The data processed for in silico trials entail the processing of personal data of individuals (notably, patients) in healthcare settings. As a consequence, privacy and data protection legislation becomes relevant. Privacy and data protection are distinct fundamental rights enshrined in the European Union’s (EU) treaties. The core and directly applicable regulation concerning the processing of personal data is the General Data Protection Legislation (GDPR). Other important data protection initiatives are undertaken by the Council of Europe and the Organisation for Economic Co-operation and Development (OECD).

• Data Governance: In healthcare and in silico trials, the sharing of data across healthcare facilities may be considered a key factor for the development, testing, and validation of in silico models. The European legislator’s and national Member States' growing interest in regulating data sharing has resulted in a new and rapidly evolving framework concerning the governance of data. The current EU legal framework on data governance includes the Open Data Directive, the Free Flow of Non-Personal Data Regulation, and the Data Governance Act. In addition to these, two legislative proposals are expected to radically change data sharing in the healthcare sector: the Data Act and the European Health Data Space.

• Clinical Trials: The legislation and regulatory documentation concerning clinical trials are relevant to the very essence of in silico trials. One of the main barriers envisaged by the In Silico World project is the lack of clear regulatory pathways for in silico trials. Illustrating the clinical trials' fundamental pieces of legislation in Europe is crucial for the project's objectives. The most relevant items of clinical trials legislation in the EU include the Declaration of Helsinki, the Declaration of Taipei, the Clinical Trials Directive, the Good Clinical Practice Directive, and the Clinical Trials Regulation.

• Medical Devices and Medicinal Products: From a product regulation perspective, in silico trials encompass medical devices and medicinal products. Concerning the first, the Medical Device Regulation and the In Vitro Medical Device Regulation are of primary importance, unitedly with the EU-level relevant bodies' guidance issued by the Medical Device Coordination Group. Concerning medicinal products, the analysis includes the Community Code for Medicinal Products for Human Use Directive 2009/94, the Advanced Therapeutic Medicinal Product Regulation, and the Health Technology Assessment Regulation.

• Artificial Intelligence (AI): It is no surprise that a fundamental component of in silico trials is artificial intelligence. The EU legal framework on Artificial Intelligence is in the process of being established. After the White Paper on Artificial Intelligence and the Guidelines on Trustworthy elaborated by the EU High-Level Expert Group on AI, the piece to monitor in the following months is the Artificial Intelligence Act. This proposal, if approved, will apply directly to all the EU Member States, and it will include general provisions of relevance to healthcare (including, for instance, medical devices) and in silico trials.

In addition to the above pieces of legislation, the study outlines the framework for forthcoming Ethics guidelines. Based on a principlist approach, these guidelines propose the analysis of four main Biomedical Ethics principles – i.e. autonomy, justice, beneficence, non-maleficence – and the secondary principle of responsibility. These principles will ultimately be beneficial for studying the fundamental ethical principles that may be used as guidance for interpreting the law and supporting stakeholders to ensure the protection and advancement of human values in the context of in silico trials.

The deliverable provides a descriptive overview of the above mentioned legal frameworks. It is prodromic to the next phases of the WP9, where the analysis will adopt an evaluative approach on legislation (D9.2, D9.3) to ultimately result in policy recommendations (D9.4).