The following impacts are expected:

• Awareness and understanding of what diversity, under-represented and underserved communities look like in geographies across Europe, including barriers and gaps to recruitment and retention in different types of clinical research, such as clinical studies¹ on medical products, clinical investigations for medical devices, and performance studies in in vitro diagnostics (IVDs), cohorts, and registries.
• Enhanced representativeness of underserved populations in clinical studies across Europe, through the building of a patient-centric, sustainable infrastructure that improves the recruitment and retention of these patients.
• Increased study data reliability and genetic diversity by including different demographic groups, thereby enhancing patient trust in the evidence generated. More patients benefit from increased access to improved innovative health technologies including medicinal products and medical devices that meet the specific needs and profiles of all patient populations.
• Promoting the implementation of new tools, solutions, approaches, or process models that will reduce the burden of clinical studies and facilitate and increase diverse patient populations’ access to clinical studies.
• Contribution to the Accelerating Clinical Trials in the EU² (ACT-EU) objectives to proactively deliver inclusive patient-oriented medicines development and delivery across populations.

_{1 Clinical study EC definition as per Horizon Europe information on clinical studies template: Clinical study covers clinical studies/trials/investigations/cohorts and means, any systematic prospective or retrospective collection and analysis of health data obtained from individual patients or healthy persons in order to address scientific questions related to the understanding, prevention, diagnosis, monitoring or treatment of a disease, mental illness, or physical condition. It includes but it is not limited to clinical studies as defined by Regulation 536/2014 (on medicinal products), clinical investigation and clinical evaluation as defined by Regulation 2017/745 (on medical devices), performance study and performance evaluation as defined by Regulation 2017/746 (on in vitro diagnostic medical devices)}

_{2 https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/accelerating-clinical-trials-eu-act-eu-delivering-eu-clinical-trials-transformation-initiative_en.pdf}

The research and innovation (R&I) action (project) to be supported under this topic should aim to deliver results that contribute to all of the following expected outcomes.

• Researchers, including industry stakeholders, clinical investigators and healthcare providers, strengthen the understanding, through use cases, of the impact of study design/protocols and study conduct on patient recruitment/retention that will help future clinical studies. These stakeholders will also benefit from gaining clarity on what clinical study diversity means in Europe, especially considering the emerging guidance from the US Food and Drug Administration (FDA) on clinical trial diversity in the US.
• Patients will benefit from a sustainable, easy-to-use digital platform, built with input from patients and/or patient support organisations, enabling more underserved patients to identify clinical studies that they are eligible for. Investigators/sites would be able to locate patients for ongoing clinical studies. This will benefit both recruitment and retention of underserved patients as it will act as a match-making portal that will be accessible to all sponsors (including academics/investigator-initiated trials, industry, etc.), and provide patient support to enable patients to allay their concerns in a timely manner, increasing their knowledge/education and building trust toward clinical research
• Researchers, including industry stakeholders, sponsors, clinical investigators, clinical research organisations, healthcare providers and patients/caregivers benefit from a toolbox of new approaches, tools, solutions and best practice approaches to facilitate and increase patient recruitment and retention, to better design and conduct clinical studies including adaptive designs, registry studies and decentralised studies with a particular focus on under-represented and underserved patient populations in Europe. Taking account of regulatory requirements, this will lead to more effective clinical studies with an increased recruitment/retention of diverse patient populations that is supported by a community-informed approach.
• Increasing population representativeness also better reflects real-world patients and helps the generalisability of the study findings, leading to better innovations. This is a positive outcome for all patients (not just underserved patients). Targeted under-represented and underserved patient populations have increased trust in clinical studies, which helps to overcome recruitment, participation, and retention challenges through educational programmes, public outreach, and community outreach/engagement.
• Clinical investigators, clinical sites and existing clinical networks benefit from cultural competency and educational training to better engage with diverse populations. New investigators from underserved communities will benefit from inclusion in clinical studies.
• The pool of clinical sites with access to diverse clinical research staff that can facilitate the education, recruitment, and retention of diverse populations in clinical studies is broadened.
• Community-based sites and organisations are better engaged to provide input on the conduct of clinical studies and to promote diversity in patient populations through inclusive enrolment practices.
• Regulators, health technology assessment bodies and payers benefit from better information on heath technologies including medicinal products, medical devices benefit-risk profile across the patient populations for use in clinical practices.
• Data standards established in agreement with regulators. Standardisation of data standards for demographic descriptors across sponsors such as race, ethnicity, gender, sex, and other selected diverse factors for the defined underserved and under-represented populations are essential for consistent reporting and valid demographic measurement.

Patient recruitment and retention remains a leading challenge in the efficient completion of clinical studies, including studies on medicinal products, medical devices, or IVDs. Furthermore, despite advancement of enrolment practices designed to better reflect the population most likely to use the health technologies in clinical practice, there is still only limited diversity within recruited patient populations. The under-representation of diverse populations (due for instance to their race and ethnicity, gender, age, socio-economic status, geographical location) creates knowledge gaps about the risks and benefits of health technologies for these specific populations.

This topic aims to develop a multi-faceted, intersectional approach to overcome the multifactorial barriers associated with the recruitment and retention of underserved patient populations in clinical studies and to contribute to transforming the way clinical studies are conducted in Europe.

To fulfil this aim, the following activities around the defined themes should be addressed.

Landscape

• Agree a definition of “underserved” populations in Europe with regulators, that includes populations facing socio-economic, systemic, or cultural barriers that prevent equitable access to clinical studies. This may be broader than populations currently defined in the demographics that sponsors collect, such as age, sex, gender, race, and ethnicity. This could include rural populations, refugees, homeless, illiterate, disabled people, and those belonging to minority populations.
• Estimate the current participation of diverse study populations in clinical studies differentiated by success in recruitment and retention; identify and evaluate the factors that contribute to and limit existing initiatives to increase diversity of recruitment and retention in clinical studies.
• Define and develop country-, social- and culture- specific understanding of factors driving under‑representation and underserved populations in Europe. Shape the development of guidance on how to reach and retain underserved populations in clinical studies in different settings and countries, and how to collect data in a GDPR¹-compliant fashion across Europe.
• Establish a sustainable patient-centric digital platform (open to all sponsors) connecting the patients, patient support organisations, sponsors, and investigators at different sites (including in community settings, hospitals, primary physicians, etc). To ensure patient engagement, the platform should use lay language and make use of existing resources such as ClinicalTrials.gov information; patient support information developed by patient organisations, or Clinical Trials Information System (CTIS). This is important to ensure that the patient/community engagement activities undertaken lead to patients being directed to use the platform, leading to an improvement in participation of diverse patients. The needs of underserved populations with access barriers to digital platforms or language barriers should be considered.
• Define the governance structure and maintenance/ownership of the platform. The active involvement of underserved patients / patient representatives is expected in the planning and development of the platform, as well as governance activities.
• Understand the interface between international, regional, and local approaches from a patient-centricity perspective (while the strategies may need to be developed and implemented locally, they will be part of multi-regional/multi-country clinical studies conducted by sponsors)

Protocol design and clinical operations

• Establish criteria for measuring ‘representativeness’, i.e. patients enrolled in the trial represent the prevalence of the disease in different sub-populations. For example:
  • Representation: age, sex, gender, race, ethnicity (measured against prevalence).
  • Inclusion: socioeconomic status, rural vs. urban access, sexual orientation, disability, payer status (private vs public), pregnancy/lactation status, etc.
• Identify and assess existing tools and solutions for patient recruitment and retention that could be used for recruitment and retention of a diverse population from a European perspective. Develop a set of suitable tools, solutions, and strategies applicable for different types of clinical studies, including studies with medicinal products, medical devices, or IVDs.
• Identify and review aspects of study design such as narrow eligibility criteria, methodological approaches, logistical and other patient-related factors that could limit broader patient and communities’ engagement, taking account of regulatory requirements; define recommendations for best practices.
• Explore and validate approaches that improve access, participation, recruitment, and retention of diverse patient populations, including innovative technology solutions, clinical research methodologies (e.g., adaptive, home based/hybrid), leveraging real world data sources etc.

Community engagement

• Raise awareness, develop educational activities and inclusive toolkits to increase knowledge and trust of target populations towards clinical studies to overcome recruitment, participation, retention challenges and to enable early patient engagement.
• Develop targeted activities to foster community engagement and build trust with patients.
• Establish connections between different stakeholders in the community e.g. researchers, industry stakeholders, patients, caregivers, investigators, and healthcare providers.

Investigators / clinical sites

• Build new site capabilities and develop training activities to increase the number of community-based sites and expand the pool of investigators, including investigators from under-represented communities and naïve investigators, to set them up in geographies where the infrastructure is missing.
• Create the necessary support mechanisms and define specialised training e.g. cultural competency training, naïve investigator training, etc. through existing clinical networks, medical institutions, patient organisations and community-based organisations. Existing resources such as Clinical Trials Transformation Initiative (CTTI), or other projects such as IMI (Innovative Medicines Initiative) projects conect4children (c4c) and EUPATI can be leveraged.

To ensure the applicability of the solutions/tools/recommendations, the applicants should test them in pilot use cases, which will be determined during the project based on the availability of cases from sponsor companies and in discussion with the consortium, in one or more disease areas of choice. The proposed disease areas should constitute an unmet public health need and a significant burden to patients, healthcare systems and society (e.g. breast cancer, prostate cancer, hypertension, lupus etc). Furthermore, the proposed areas should be representative to allow broad implementation across diverse disease areas, different cultural and geographical distributions, types of clinical research such as clinical studies on medical products, clinical investigations for medical devices, performance studies for IVDs, and studies testing non‑pharmacological and rehabilitation interventions.

The purpose of the pilot use cases is to test tools and solutions for patient recruitment and retention, assess the functionality of the digital platform, and test the improvements brought by the digital platform on patient recruitment and retention. The focus will be on testing the robustness of the infrastructure to ensure the solutions put in place are “fit for purpose”. The testing could establish the viability of the solutions, for example:

• number of new sites added to the platform;
• number of under-represented investigators trained through this initiative;
• number of investigators that serve underserved patient populations;
• effectiveness of community engagement activities as judged by patient support organisations;
• effectiveness of recruitment and retention activities via the platform, as experienced by investigators and patients;
• analysis of number of users of the platform and the type of content accessed by users.

Applicants are expected to consider the potential regulatory impact of the results and as relevant develop a strategy/plan for generating appropriate evidence, and to engage with regulators in a timely manner (e.g., through the EMA Innovation Task Force, qualification advice).

In their proposals, applicants should leverage and build on existing tools & solutions and best practice experiences that have already been developed at national European and/or international level, including tools developed in IMI/IHI projects.

_{1 General Data Protection Regulation}