Periodic Reporting for period 2 - HYBRIDA (Embedding a comprehensive ethical dimension to organoïd-based research and resulting technologies)
Periodo di rendicontazione: 2022-08-01 al 2024-07-31
The HYBRIDA project has investigated three types of uncertainty, in relation to organoid research and organoid-related technologies with the aim to co-develop guidance for researchers, members of Research Ethics Committees, Research Integrity Offices, research funders, and regulators. HYBRIDA emanated from the fact that since Roman law, all entities have been categorized and regulated either as persons or as things (subjects or objects) and from the recognition that this conceptual, epistemological and regulatory dualism is currently being challenged by disruptive research and innovation, among which organoid research is a prominent example. This dualistic normative framework is disrupted by three different kinds of uncertainty: conceptual uncertainty, epistemological and methodological uncertainty, and regulatory uncertainty.
HYBRIDA project contemplated on the first type of uncertainty with the outputs of WP1 (https://hybrida-project.eu/deliverables/). The complex questions of the second type of uncertainty were addressed in the context of WP2. Initially, conducted a thorough mapping of the research landscape of organoid and organ-on-chip models. Then, HYBRIDA tackled the questions that relate to the application of a HTA, with a series of three deliverables that culminated to an amended HTA to evaluate organoids as emerging technologies in the clinic. The questions related to the third type of uncertainly received response by the four main outputs of HYBRIDA:
• Operational guidelines: Recommendations to organoid researchers, designed to streamline certain working procedures according to best practices. The operational guidelines are structured along the following, main parts that aim to help researchers ensure reliable research, development and production of organoids and related technologies and provides advice on assessment and evaluation of organoid research projects: MIAOU (Minimal Information about Organoids and their Use for Researchers), EChOES (Evaluator Checklist for Organoid Experimental Studies), RICOCheck (Research Integrity Committee Organoid Checklist), and TRUSTED (Donor’s Tissue Research Under Secure Transparent Ethical Donation).
• Code of Responsible Conduct for researchers: Ethical standards of good practice to guide organoid researchers.
• Supplement to the ECoC: Criteria for proper research practice and self-regulation in the field of organoids.
• Enhancement of existing ethics and normative frameworks: Compilation of the normative bedrock of the organoid field and analysis of the amount of risk and forms of uncertainty society is willing to accept in relation to different organoids.
These four outputs provide responses on WHY is there a need to enhance existing ethics and regulatory frameworks, on WHAT standards of conduct and good practices to follow to be in line with the enhanced ethics and regulatory frameworks, and on HOW to implement these new standards and good practices. Each question has been answered by the above main outputs of HYBRIDA, as it is graphically represented by the figure.
With regard to the exploitation of HYBRIDA’s results, the following points must be noted:
• HYBRIDA’s outputs that were delivered in the context of WPs 5 and 6 are going to be utilized for the didactic needs of the “Training for organoids modelling physiology and pathology in the human gastrointestinal tract (TOPGUT)” MSCA Doctoral Network, funded by the European Commission under the topic HORIZON-MSCA-2022-DN-01-01 (No. 101119911). Specifically, the doctoral candidates of TOPGUT are going to be trained in issues related to Research Ethics, Law, Research Integrity, and responsible communication, in the context of the Individual Research Project No. 10, entitled: “The ethics and law of gastrointestinal models”. A doctoral candidate has already started her PhD on a relevant to Research Project 10 topic at the University of Oslo that is consortium partner of TOPGUT.
• The questionnaire that has been developed in the context of MIAOU, as part of HYBRIDA’s Operational Guidelines, has been released also as a web-application. In this form it is available at the French “The GDR Organoids” (https://gdr-organoides.cnrs.fr/) and will be implemented at the European Bank for induced pluripotent Stem Cells – EbiSC (https://ebisc.org/) and at the Human pluripotent stem cell registry - hPSCreg (https://hpscreg.eu/). These three entities will provide a very visible display of HYBRIDA’s output and boost the use of MIAOU, raising the possibility of a positive spillover effect for the visibility of all other outputs of the project.
With regard to the dissemination of HYBRIDA’s results, the following points must be noted, which act as multipliers of the dissemination strategy of the project:
• The Operational Guidelines of HYBRIDA, which is a 137-page document, has been also released in the form of an 13-page executive summary (see: https://hybrida-project.eu/executive-summaries/). Additionally parts of the Operational Guidelines have been released as concise “pocket-size” guidance documents that focus on the following topics: (a) Informed consent for research on organoids and related fields and (b) Guide for the use of questionnaires (see: https://hybrida-project.eu/executive-summaries/). These concise documents provide an opportunity to the potential end user to have a relatively quick overview of the content of the Operational Guidelines and some deeper insights of specific topics, without having to go through the rather lengthy D5.1.
• The development of D2.4 has utilized empirical data that were gathered by conducting 10 interviews with key actors associated with projects at the cutting edge of clinical translation (representing - what was termed from WP2 members - the “epistemological hotspots” of organoid translation). This survey – that was not initially planned – provided an important display of HYBRIDA project and its outputs at a stakeholder type that is usually significantly challenging to engage with.
• A dissemination strategy, via HYBRIDA’s social media channel, has been developed for boosting the visibility of HYBRIDA’s outputs that is planned to initiate as soon as all deliverables will have been reviewed by the external expert evaluator and accepted by the Project Officer, and Policy Officer.
• Operational guidelines: Recommendations to organoid researchers, designed to streamline certain working procedures according to best practices. The operational guidelines are structured along the following, main parts that aim to help researchers ensure reliable research, development and production of organoids and related technologies and provides advice on assessment and evaluation of organoid research projects: MIAOU (Minimal Information about Organoids and their Use for Researchers), EChOES (Evaluator Checklist for Organoid Experimental Studies), RICOCheck (Research Integrity Committee Organoid Checklist), and TRUSTED (Donor’s Tissue Research Under Secure Transparent Ethical Donation).
• Code of Responsible Conduct for researchers: Ethical standards of good practice to guide organoid researchers.
• Supplement to the ECoC: Criteria for proper research practice and self-regulation in the field of organoids.
• Enhancement of existing ethics and normative frameworks: Compilation of the normative bedrock of the organoid field and analysis of the amount of risk and forms of uncertainty society is willing to accept in relation to different organoids.
These four outputs provide responses on WHY is there a need to enhance existing ethics and regulatory frameworks, on WHAT standards of conduct and good practices to follow to be in line with the enhanced ethics and regulatory frameworks, and on HOW to implement these new standards and good practices. Each question has been answered by the above main outputs of HYBRIDA, as it is graphically represented by the figure.
With regard to the exploitation of HYBRIDA’s results, the following points must be noted:
• HYBRIDA’s outputs that were delivered in the context of WPs 5 and 6 are going to be utilized for the didactic needs of the “Training for organoids modelling physiology and pathology in the human gastrointestinal tract (TOPGUT)” MSCA Doctoral Network, funded by the European Commission under the topic HORIZON-MSCA-2022-DN-01-01 (No. 101119911). Specifically, the doctoral candidates of TOPGUT are going to be trained in issues related to Research Ethics, Law, Research Integrity, and responsible communication, in the context of the Individual Research Project No. 10, entitled: “The ethics and law of gastrointestinal models”. A doctoral candidate has already started her PhD on a relevant to Research Project 10 topic at the University of Oslo that is consortium partner of TOPGUT.
• The questionnaire that has been developed in the context of MIAOU, as part of HYBRIDA’s Operational Guidelines, has been released also as a web-application. In this form it is available at the French “The GDR Organoids” (https://gdr-organoides.cnrs.fr/) and will be implemented at the European Bank for induced pluripotent Stem Cells – EbiSC (https://ebisc.org/) and at the Human pluripotent stem cell registry - hPSCreg (https://hpscreg.eu/). These three entities will provide a very visible display of HYBRIDA’s output and boost the use of MIAOU, raising the possibility of a positive spillover effect for the visibility of all other outputs of the project.
With regard to the dissemination of HYBRIDA’s results, the following points must be noted, which act as multipliers of the dissemination strategy of the project:
• The Operational Guidelines of HYBRIDA, which is a 137-page document, has been also released in the form of an 13-page executive summary (see: https://hybrida-project.eu/executive-summaries/). Additionally parts of the Operational Guidelines have been released as concise “pocket-size” guidance documents that focus on the following topics: (a) Informed consent for research on organoids and related fields and (b) Guide for the use of questionnaires (see: https://hybrida-project.eu/executive-summaries/). These concise documents provide an opportunity to the potential end user to have a relatively quick overview of the content of the Operational Guidelines and some deeper insights of specific topics, without having to go through the rather lengthy D5.1.
• The development of D2.4 has utilized empirical data that were gathered by conducting 10 interviews with key actors associated with projects at the cutting edge of clinical translation (representing - what was termed from WP2 members - the “epistemological hotspots” of organoid translation). This survey – that was not initially planned – provided an important display of HYBRIDA project and its outputs at a stakeholder type that is usually significantly challenging to engage with.
• A dissemination strategy, via HYBRIDA’s social media channel, has been developed for boosting the visibility of HYBRIDA’s outputs that is planned to initiate as soon as all deliverables will have been reviewed by the external expert evaluator and accepted by the Project Officer, and Policy Officer.
The in-depth mapping of the organoid field had not been done before. It provided a good evidence base for the co-development of guidelines for organoid researchers and for enhancing existing normative frameworks and regulations. The amended HTA was created with the development of novel methodological elements, which culminated in the amended HTA to evaluate organoids as emerging technologies in the clinic. “Vision assessment” was decided as the foundation of the method that was applied and WP2 members elaborated on this framework to develop a strategy suited for organoids and organs-on-chip, especially in the context of clinical medicine and personalized medicine. HYBRIDA, in the context of its Operational Guidelines is proposing a holistic approach that prioritizes the concerns of individuals, emphasizing ethical self-assessment (RICOCheck), informed consent with a detailed list of donor options (TRUSTED), ensuring responsible and ethically informed organoid research and application.