Improving implementation of innovations in treatment for cardiovascular disease in low- and middle-income countries: the IMPLEMENT-CVD Study

Background:
Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD causes almost 18 million deaths each year, 10 million of which are caused by high blood pressure, or hypertension (blood pressure > 140/90 mm Hg). Four out of five CVD deaths occur in low-and middle-income countries (LMICs), and half of these are among people under 70 years of age. The high number of CVD deaths in LMICs can be largely explained by gaps in treatment. Low drug availability, high costs of treatment and treatment complexity are among the leading barriers to hypertension and CVD treatment use in LMICs, and that the poorest are the most affected by these barriers.
Fixed-dose combination (FDC) therapies for treatment of hypertension (2-3 blood pressure lowering medications combined into one pill) or secondary prevention of CVD (2 blood pressure-lowering medications, a statin, with or without aspirin) are an innovation in drug treatment that offer a safe and effective solution for addressing known barriers to treatment such as treatment complexity and cost. FDCs for hypertension were added to the WHO Essential Medicines List in 2019 and evidence is building for the addition of FDCs for secondary prevention of CVD.

Aim and Objectives:
The overall aim of this research is to understand and address the factors affecting implementation of fixed-dose combination therapy for primary and secondary prevention of CVD in LMICs, focusing on the case of Kenya. Implementation here is defined as "active and planned efforts to mainstream an innovation within an organisation or system".

Drawing on implementation frameworks and theories developed in the UK, my objectives are:
1. To identify the health system factors and the interactions between them affecting implementation of FDCs for hypertension and CVD in Kenya.
2. To design evidence-based implementation strategies for FDCs for hypertension and CVD.
3. To assess the feasibility of these implementation strategies.
4. To adapt implementation research frameworks and theories developed in the UK to addressing these questions in a LMIC context and
to share insight and tools for their adaptation to this purpose.
5. To evaluate the effectiveness and cost-effectiveness of the implementation strategy.
6. To adapt and apply the study tools to the development and evaluation of implementation strategies in other contexts with high CVD burden and low use of treatment.
7. To engage key stakeholders throughout the research process to ensure the relevance of the research for the Kenyan context and its impact more globally.

Methods:
This programme of research will include 5 work packages. WP 1-3 will take place in Years 1-4 and WP 4 and 5 in years 5-7.
WP 1 will use document review, secondary data analysis and qualitative interviews to identify factors affecting implementation of FDCs in Kenya, using the NASSS implementation framework developed in the UK.
WP2 will use findings from WP1 and the best available evidence to co-create an implementation strategy with key stakeholders, including components at all levels of the health system, and to develop at Theory of Change;
WP3 will evaluate the strategy: i) the feasibility of health service level components will be evaluated using a pilot intervention at 2 health facilities in Trans Nzoia and Busia counties in Kenya; ii) the feasibility of policy components will be evaluated using stakeholder analysis.
WP4 will evaluate the effectiveness and cost-effectiveness of the implementation strategy.
WP5 will apply the adapted frameworks and data collection tools used in this research to other LMIC where CVD burden is high and implementation of FDCs is low.

Impact:
This research stands to have a significant impact on CVD policy in LMICs and implementation research approaches. I will engage stakeholders throughout the research process to ensure this impact is achieved.

The research I am proposing has the potential to make a significant impact on multiple levels.

First, it will contribute toward reducing the burden of cardiovascular disease (CVD) in Kenya where where there is a high burden of hypertension and CVD and treatment rates are very low. It will do so by providing a detailed understanding of factors affecting implementation of a proven innovation in hypertension and CVD treatment - fixed dose combination therapy (FDCs) - and designing and testing a strategy to address these. The Ministry of Health (MoH) has made a commitment to advancing management of hypertension and CVD in Kenya. FDCs can be a key tool in achieving this goal. The country has a favourable environment for conducting implementation research, with strong political commitment to improving public health; transparency of plans and strategies and opportunities for refining and scaling up new approaches. This presents a window of opportunity to influence policy.

My research will also have an impact more globally. In 2014 the World Health Organization (WHO) and its member states set an ambitious goal of reducing premature mortality from CVD by 25% by 2025, with targets to reduce hypertension prevalence, increase medicine availability, and improve treatment rates. We are far from reaching these targets and new approaches are urgently needed. The research I am proposing will a crucial step toward identifying a new approach in LMICs, by providing a framework and implementation strategy that can be adapted to other LMIC settings. I have already discussed the applicability and relevance of this research with colleagues in India, Zimbabwe and Peru, where the burden of CVD is high, and implementation of effective treatments is poor, and where I have strong links to research collaborators.

Finally, my research will have an impact on the fields of health systems and implementation research by adapting and applying existing frameworks and theories, developed in the UK, to new questions and contexts, thus advancing theoretical knowledge. My work will be the first to adapt and apply the NASSS framework (Non-adoption, abandonment, challenges to scale-up, spread and sustainability) and Normalisation Process Theory and Burden of Treatment theory to the question of implementation of pharmaceutical innovations in LMICs. The lessons and tools resulting from this work will be of value to other health systems and implementation researchers globally, as well as those developing and scaling up innovative approaches to CVD and chronic disease treatment.