This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination 3 “Tackling diseases and reducing disease burden”. To that end, proposals under this topic should aim for delivering results that are directed, tailored towards and contributing to some of the following expected outcomes:

• Health care practitioners and providers in low- and middle-income countries (LMICs) and/or those in high-income countries (HICs) serving disadvantaged populations have access to and use specific guidelines to implement health interventions that improve the availability of effective, equitable, efficient, integrated, patient-centred, safe, and timely care and the overall quality of life for people living with multiple long-term conditions including non-communicable diseases (NCDs).
• Public health managers and authorities, including from other relevant sector (e. g., social, culture) have access to improved insights and evidence on how to decrease the fragmentation of care for patients living with multiple chronic conditions, and ensure continuity of care across all stages of disease progression. They use this knowledge to design policies to reduce health inequities.
• Adopting an implementation science approach to studying interventions for management of multiple long-term conditions in the context of NCDs, researchers, clinicians and authorities have an improved understanding how the proposed interventions could be adopted in LMICs and/or disadvantaged populations of HICs setting, taking into account specific social, political, economic and cultural contexts.
• Communities and local stakeholders and authorities are fully engaged in implementing and taking up interventions for management of multiple long-term conditions in the context of NCDs and thus contribute to deliver better health.

The European Commission is a member of the Global Alliance for Chronic Diseases (GACD)^[1], an alliance of international funding agencies representing over 80% of the world’s public health research funding and the first collaboration of its kind to specifically address NCDs. The GACD supports implementation science to improve health outcomes. This topic is launched in concertation with the other GACD members and aligned with the 9^th GACD call.

The topic is focused on implementation research for management of multiple long-term conditions in the context of NCDs (MLTC NCD) in LMICs and/or disadvantaged populations in HICs. Proposals should focus on implementation science around interventions that will generate evidence about when, for whom, and under what circumstances, patient-centred approaches can improve integrated care for patients with MLTC NCD.

MLTC NCD refers to the co-occurrence of multiple chronic conditions, at least one of which is an NCD. NCDs include for example cardiovascular diseases, chronic respiratory diseases, cancers, musculoskeletal disorders, diabetes, hypertension, haematological disorders, sleep disorders, and mental health disorders. The high prevalence of MLTC NCD is projected to rise with the ageing population and the increasing burden of NCDs. MLTC NCD has a profound impact on patients, and is associated with premature death, physical disability, substance abuse, poor quality of life, mental health issues, and financial difficulties from high costs of care. It is also associated with difficulties in adherence to and high rates of adverse effects from treatment with multiple medications. In addition, due to poor health and the complexity of managing their conditions, patients with MLTC NCD are high utilisers of health care systems, which is especially challenging in low-resourced contexts.

Addressing MLTC NCD demands a shift from fragmented models of care, which treat individual health issues separately as they occur, to a more holistic integrated care model that provides a whole person focus on health management^[2]. The current evidence suggests that primary healthcare^[3], integrated and coordinated care, patient-centred interventions, digital health technology, and optimised medication therapy are key to improved management of MLTC NCD. However, implementing patient-centred strategies for treating MLTC NCD remains challenging and largely unexplored in disadvantaged contexts, especially in LMICs. Adapting and scaling such models is critical to improving quality of life; reducing disability; reducing the burden of caretaking on (typically female) family members and reducing health system costs.

The proposed implementation research must focus on one or more evidence-based interventions (or complex interventions) known to promote integrated management of multiple long-term conditions, including NCDs. It should assess patient-centred interventions focused on patient management or self-management, or interventions that transform communities, clinical practice, and/or health systems. Applicants should justify the choice of intervention(s) and provide evidence of the intervention’s effectiveness, acceptability, feasibility, and potential for long-term health and other impacts. Ideally, evidence of the intervention’s real-world effectiveness should be supported by a well-conducted systematic review where available. As the evidence for how to manage MLTC NCD is still emerging, particularly in LMICs, a limited period of testing the effectiveness of an intervention that the applicant’s team has adapted for local implementation is therefore usually appropriate.

Applicants must explore the implementation of proposed intervention(s) for a selected study population(s) taking into account the unique social, political, economic, and cultural context(s) in which the study will take place. Applicants should justify why any adaptation will not compromise the known effectiveness of the selected intervention(s).

Proposals should address all of the following activities^[4]:

• Provide a research plan using validated implementation research frameworks or hybrid design research;
• Have an appropriate strategy for measuring implementation research outcomes and real-world effectiveness outcomes and indicators;
• Specifically address health equity and the principles of Universal Health Coverage^[5];
• Engage an appropriately expert and skilled research team which can ensure a suitable multidisciplinary approach and that demonstrates equitable partnership and shared leadership between HIC-LMIC, and/or non-Indigenous–Indigenous members of the project team and external stakeholders through a clear governance strategy;
• Provide a stakeholder engagement strategy with evidence of support/engagement from key stakeholders for delivering patient-centred care and a pathway to sustain the proposed intervention after the funding ends;
• Provide opportunities for implementation research capacity building for early career researchers and team members from lower resourced environments, such as LMICs or disadvantaged communities.
• Ensure meaningful involvement of early career team members, including at least one early career member as a co-investigator.

Applicants are also encouraged to follow a life course approach, adapting the intervention to one or more key life stage(s) critical for reducing the onset or progression of MLTC NCD, and to explore how to best implement digital technology interventions.

The study population may include patients with existing MLTC NCD, or existing NCDs (e.g., studies focusing on rolling out screening services for multiple NCDs). The study population may also include patients with chronic infectious disease(s) (e.g., studies that focus on integrating NCD management into an HIV or tuberculosis clinic) or a mixture of both.

The following are potential interventions or strategies that applicants may consider in their implementation plan (please note that this is not an exhaustive list):

• Strategies for improving MLTC NCD identification, stratification/staging, management, and/or monitoring such as investigating strategies for adapting and implementing the protocol(s) described in the WHO Package of Essential NCD Interventions (WHO PEN)^[6] that address MLTC NCD management. For example, projects may focus on integrating NCD care into clinics that typically focus on the management of infectious diseases, such as HIV or tuberculosis clinics, or the integration of NCD care into maternal and child health clinics;
• Strategies to streamline and improve quality of care among individuals with MLTC NCD to reduce fragmentation of services, including task-sharing and/or the use of clinical decision-making tools (e.g., digital tools);
• Strategies and/or tools (e.g., digital tools) that optimise appropriate medication and (non-pharmacological) therapeutic prescribing, adherence, and/or reduced drug interactions/ adverse effects;
• Interventions that improve transitions through the health system, from community to primary to tertiary care and beyond, such as to home care or hospice;
• Health behavioural change interventions that target different risk factor clusters (e.g., exercise, nutrition, tobacco, alcohol and substance abuse).

The proposal’s primary outcome measures must be implementation research outcomes to assess MLTC NCD. With regard to MLTC NCD, applicants are encouraged to explore any combination of chronic conditions, including mental health disorders and sleep disorders. The specific combination of conditions should be justified using local or regional epidemiological data about their co-occurrence. Outcome measures should appropriately address implementation tackling MLTC NCD, and not focus on one condition. Proposals may also contain a strategy for measuring other secondary outcomes (or proxy outcomes) that demonstrate the intervention’s real-world effectiveness in the local context and target populations. Additionally, other health or non-health outcome measures, especially those identified as important by patient participants and/or critical for advancing Universal Health Coverage, are also welcome.

Poverty, racism, ethnic discrimination, and other inequities are directly associated with reduced potential for equitable access to quality care. Proposals should consider the social determinants of health and discuss their potential impact on the effective implementation of the intervention(s). If there is a focus on a particular population (e.g., gender, ethnicity), then the reason for this should be justified.

In order to promote health equity, proposals should aim to address differences in intervention access, uptake, and effectiveness in socially disadvantaged groups and develop strategies for reducing inequities. To facilitate this process at the data analysis stage, studies should be designed to address such differences. At a minimum, studies should capture sex and/or gender differences. If feasible, a plan for capturing intersectional impacts on health outcomes should be included in the analysis strategy.

This topic requires the effective contribution of social sciences and humanities (SSH) disciplines and the involvement of SSH experts, institutions as well as the inclusion of relevant SSH expertise, in order to produce meaningful and significant effects enhancing the societal impact of the related research activities.

For implementation research to have a strong likelihood of being taken up into policy or practice and informing the scale up of effective interventions, it is vital that project teams engage the appropriate stakeholders. Proposals should present a strategy to include the relevant decision makers such as policymakers, ministry officials, local authorities, non-governmental organisation leaders, community leaders as well as other stakeholders such as community groups, or other individuals or organizations involved in the implementation of the intervention, from the development to the implementation knowledge translation phase. It is also important to include stakeholders who can help sustain the project’s implementation, facilitate scale up, and use the knowledge generated from the project after the grant ends.

Stakeholders also include patients, their family members and carers. Their contributions should be nurtured through meaningful engagement from the outset, not only as participants in the research undertaken. Patient engagement throughout the research project is critical to developing patient-centred models of care.

All projects funded under this topic are strongly encouraged to participate in networking and joint activities, including internationally, as appropriate. These activities could, for example, involve the participation in joint workshops, the Annual Scientific Meetings of the GACD, the exchange of knowledge, the development and adoption of best practices, or joint communication activities. Therefore, proposals are expected to include a budget for such activities and may consider covering the costs of any other potential joint activities without the prerequisite to detail concrete joint activities at this stage. The details of these joint activities will be defined during the grant agreement preparation phase.

Applicants envisaging to include clinical studies should provide details of their clinical studies in the dedicated annex using the template provided in the submission system. See definition of clinical studies in the introduction to this work programme part.

[1] https://www.gacd.org/

[2] In keeping with the principles of Universal Health Coverage, the World Health Organization advocates that health systems move towards offering a continuum of quality NCD preventative, diagnostic, curative, rehabilitative, and palliative care services, that are available and accessible to all, independent of economic circumstances.

[3] https://www.who.int/news-room/fact-sheets/detail/primary-health-care

[4] The following types of projects will NOT be funded: i) proposals focused on primary prevention of NCDs or other chronic conditions; ii) proposals with the primary aim of informing the development and/or selection of an intervention for a given context, where the implementation component will be explored in a future project; iii) epidemiological cohorts; iv) etiological work, mechanistic, or epidemiological research, unless an essential component of a focused study to develop implementation research approaches; v) clinical trials, validation studies, or intervention efficacy studies for a new or established pharmacological agent or behavioural intervention.

[5] https://www.who.int/health-topics/universal-health-coverage

[6] https://www.who.int/publications/i/item/9789241598996