Actions under this topic are expected to achieve the following impacts:

• New clinically-validated biomarker-driven approaches are available that lead, as relevant, to more precise and effective diagnosis, leaner diagnosis-to-treatment pathways, better treatment path selection, or improved follow-up and treatment response assessment and monitoring.
• A significant reduction in the diagnostic or therapeutic burden for patients (and caregivers) for example by favouring non- or minimally-invasive approaches.
• Validated tools and approaches supporting evidence-based health and care decisions addressing both the needs of patients and of healthcare systems.
• An increase in the competitiveness of European health industries.

Actions under this topic must contribute to all the following expected outcomes:

• Access for healthcare professionals to novel, robust and fit for purpose biomarkers¹ with linked technologies enabling their use in clinical setting and progress towards validation. Biomarkers and linked technologies may be for diagnosis, monitoring disease progression, selecting the optimal therapeutic treatments, or assessing treatment response.
• Availability for researchers of robust and fit-for-purpose biomarkers with linked technologies enabling their clinical use for diagnosing disease, disease monitoring, or monitoring treatment response. This will enable researchers to develop safer and more effective personalised treatments tailored to the individual’s characteristics and the stage of their disease. Alternatively, availability for researchers of key technology (e.g. companion diagnostics) that could be essential for the safe and appropriate use and selection of a corresponding drug or biological product or its development.
• Availability for regulators of robust evidence on the suitability of selected biomarkers and their linked technologies to enable regulatory acceptance for a specific use.

¹ _{See definition as in the IHI JU Strategic Research and Innovation Agenda (Glossary): BIOMARKERS are biological characteristics, which can be molecular, anatomic, physiologic, or biochemical. These characteristics can be measured and evaluated objectively. They act as indicators of a normal or a pathogenic biological process. They allow the assessment of the pharmacological response to a therapeutic intervention. A biomarker shows a specific physical trait or a measurable biologically-produced change in the body that is linked to a disease or a particular health condition. A biomarker may be used to assess or detect a specific disease as early as possible (diagnostic biomarker), the risk of developing a disease (susceptibility/risk biomarker), the evolution of a disease (prognostic biomarker) – but it can also predict response to a given treatment including potential toxicity (predictive biomarker).}

Biomarker-driven approaches for diagnosis, monitoring disease progression and assessing treatment response have immense potential to help us progress precision medicine. Despite intense research, few biomarkers are subject to rigorous testing in clinical settings and shown to be fit for purpose (clinically validated). In addition, while there are several novel biomarkers that have shown significant promise for a number of use cases, often the technology to make them accessible for clinical use is not mature enough, which hampers their validation for use. Thus, technology development or improvements to existing technologies may be required to progress these biomarkers to clinical validation. For example, there are many novel and highly innovative technologies in development (e.g. imaging, artificial intelligence (AI), omics markers, phage-based diagnostics in multiple formats among others) and their further development and validation would be a necessary element for validating their detected biomarkers in the clinic.

Furthermore, different healthcare actors (e.g. academics, clinicians, patients, health technology developers and regulators) may have different definitions and expectations on the utilities of biomarkers, and there is a need for an aligned methodological framework for scaling up the clinical validation of candidate biomarkers.

To address this challenge, this topic aims:

• to progress candidate biomarkers towards clinical validation and, when relevant, to regulatory acceptance;

and/or

• to progress towards clinical validation innovative technologies necessary for making biomarker(s) accessible for clinical use. In proposals focusing uniquely on these technologies, applicants should justify how such progress will enable the validation of the biomarker(s) for use in a clinical context.

Projects funded under this topic should:

• Assemble a cross-sectoral public-private partnership to align and develop a methodological framework and roadmap for progressing selected candidate biomarker(s) and/or linked technologies enabling the clinical use of the biomarker(s) (or a combination thereof) to rigorous clinical validation
• Provide a justification and clearly demonstrate why the proposal area responds to an unmet public health need¹.
• Progress biomarker(s) and/or technologies towards clinical and analytical validation in one or more of these areas: diagnosing disease, early treatment path selection, monitoring disease progression, or treatment response assessment:
  • All types of biomarkers including digital, combinations of biomarkers and multimodal biomarkers are in scope. Proposals addressing biomarker(s) intended for specific populations such as the elderly or children are very welcome.
  • The candidate biomarkers can be combined with existing biomarkers for more personalised decision making.
  • All types of technologies for progressing biomarkers to a stage closer to clinical validation, including innovative and novel approaches, are in scope. Some examples could be technologies for the effective collection, preparation, measurement and analysis of samples and biomarkers, or diagnostic equipment, methods, or systems.
  • In their proposal, applicants must clearly identify the candidate biomarker(s) and/or linked technology(ies) and the proposed application in research and development (R&D) and/or clinical practice.
  • Applicants should provide in their proposal sufficient preliminary evidence, including relevant methodology(ies) and high-quality data to demonstrate that the biomarker(s) and/or technology(ies) can be progressed towards clinical validation and, when relevant, to regulatory acceptance.
  • As relevant, applicants must ensure effective collection, preparation, measurement, and analysis of biomarker samples to allow validation in the clinical setting.
• Build on existing solutions to develop a collaborative platform to integrate, analyse and share data (historical or generated de novo) gathered for the validation of biomarker(s) and/or linked technologies during the project, as well as to support future biomarker validation beyond the project duration. Applicants should plan to ensure the future scalability and sustainability of the platform and future data sharing and ensure adherence to FAIR (findable, accessible, interoperable, reusable) principles.
• Develop a regulatory strategy and interaction plan for evidence generation to support the regulatory qualification of the biomarker/s and/or technologies and engage with regulators in a timely manner (e.g. national competent authorities, European Medicines Agency (EMA) Innovation Task Force, qualification advice). Applicants should reserve resources to support these interactions.
• Elaborate a plan for interacting with all the relevant actors in the learning healthcare system (for example clinicians, academic researchers, healthcare professionals, health technology developers, regulators, policy makers, and others as relevant) to align on utilities of the candidate biomarker(s) and/or technologies for clinical use and guide the roadmap.
• Disseminate the results of the project to ensure uptake by relevant stakeholders, including healthcare systems and technology developers.
• Applicants should also reserve resources to synergise with other relevant initiatives, including other projects funded under this topic and those funded under IHI Call 3 topic 1² as relevant.

¹ _{See definition in Art 125.1 of the Council Regulation (EU) 2021/2085 establishing the Joint Undertakings under Horizon Europe: “An unmet public health need shall be defined as a need currently not addressed by the health care systems for availability or accessibility reasons, for example where there is no satisfactory method of diagnosis, prevention or treatment for a given health condition or if people’s access to health care is limited because of cost, distance to health facilities or waiting times.”}

^{2 _{https://www.ihi.europa.eu/apply-funding/ihi-call-3}}