Title: Cost-effectiveness of statin therapies evaluated using individual participant data from large randomised clinical trials
Funder: Department of Health and Social Care

Abstract: There is a clear relationship between high cholesterol levels and the risk of heart disease and stroke. Statins are a group of prescription medicines that can help to lower cholesterol levels and decrease the risk of heart attacks and strokes. Statins are currently widely prescribed for people in the UK and, in most cases, treatment with statins continues for life. This is based on good evidence that statins are safe and effective for preventing cardiovascular disease. However, there is some uncertainty about whether statins are appropriate for all types of people, especially those at low risk. This study will provide the most detailed assessment to date of the effects of statins on life expectancy and quality of life, as well as their value for money, in a wide range of different types of people._x000D_ _x000D_ The study will draw on detailed information from three separate large databases: the Cholesterol Treatment Trialists’ (CTT) Collaboration database (including around 180,000 people in whom effects of stains were reliably studied), the UK Biobank study (around 500,000 people in the UK providing detailed data for research) and the Whitehall II study (a 10,000-person UK cohort with about 30 years follow-up). All these databases include information on how cardiovascular disease develops over time in different types of people. In particular, the large CTT database includes reliable data about the effects, both beneficial and adverse, of different statins on people’s health. _x000D_ _x000D_ We will use the CTT, the UK Biobank and the Whitehall II databases to develop a reliable computer model that will predict future heart attacks, strokes and deaths and effects of statins on these and other disease events in different types of people. UK Biobank data will also be used to assess healthcare costs, whilst information on quality of life experienced by people with and without heart disease and stroke will be informed from external sources, thereby allowing the effects of these events to be studied in the computer model. We will use this model to calculate how long people can expect to live, their quality of life, and the costs of healthcare, depending on whether they take or do not take a statin. This model will be incorporated into a user-friendly computer ‘app’ that will enable managers, analysts, doctors and members of public to calculate the long-term effects of statins._x000D_ _x000D_ Throughout the project, we will discuss our methods and emerging results with our advisory panel which includes a public and patient representative, a cardiologist, a statistician, a health economist and a public health physician. Given the importance of the study, we will also present and discuss our findings more widely with doctors, policy makers and the general public. We will make the computer model freely available for further use. We expect our findings to directly inform future statin prescribing guidelines.

Lay abstract: Research question: What are the long-term effects and cost-effectiveness of statin therapies in categories of patients, evaluated using individual participant data from large randomised clinical trials?_x000D_ _x000D_ Background: Cholesterol-lowering “statin” therapy reduces heart attacks and strokes, saves lives, and is considered “good value” for people at increased risk of cardiovascular disease (CVD). In the UK, statins are recommended for people with an annual CVD risk of at least 1%. However, uncertainty remains as to the cost-effectiveness of statins in different categories of people, such as those at lower or medium risk, the young or elderly, and women._x000D_ _x000D_ Aims and objectives: We propose to use the detailed data from 3 main sources to produce definitive evidence in relation to the cost-effectiveness of statins in categories of patients in the UK. These are: (i) the Cholesterol Treatment Trialists’ (CTT) Collaboration database including approximately 180,000 participants in 28 large randomised trials of statin therapy; (ii) the UK Biobank database of approximately 500,000 people; and (iii) the Whitehall II study database including approximately 10,000 people. _x000D_ _x000D_ Methods: First, we will use the individual participant data (IPD) in the CTT database, and long-term follow-up data for some of the trials, to develop the CTT cost-effectiveness model. This model will project the morbidity, mortality, healthcare costs and health-related quality of life (QoL) for individual patients over time, and the effects of particular statin regimens on each of these (Work Package (WP) 1). Second, we will use the UK Biobank, linked to routine healthcare data, and, separately, the Whitehall II study data to validate the CTT model, ie, to compare the predictions from the model with the number of cardiovascular events actually experienced, and, if necessary, to adjust the model to improve its performance (WP2). Third, we will use the UK Biobank data to evaluate the impact of cardiovascular (eg, heart attacks and strokes) and other disease (eg, diabetes) events on healthcare costs and will source the effects of these cardiovascular and other disease events on patients’ QoL from external data (WP3). Results from WP3 will provide data on the costs and QoL associated with events in the CTT model. Fourth, we will use the validated CTT model to assess the net health effects, healthcare costs, and cost-effectiveness of different statin regimens in categories of participants in UK Biobank by age, gender, cardiovascular disease risk, and other characteristics of interest (WP4). Finally, we will develop a user-friendly web interface to enable external use of the model by analysts, professionals and members of public to simulate long-term outcomes and cost-effectiveness of statins (and other cardiovascular preventive interventions) for individual patients and population groups (WP5). Throughout the project we will discuss our plans, progress and results with members of our advisory panel of Patient and Public Involvement (PPI) representatives, practitioners and public health specialists, and will use the feedback received in further project development._x000D_ _x000D_ Timelines for delivery: The project will be conducted over 36 months. _x000D_ _x000D_ Anticipated impact and dissemination: The findings from this project will play an important role in informing statin prescription guidelines for cardiovascular disease prevention. The CTT model and all risk, QoL and costs models, developed as part of the project, will be fully published and made freely available for external use.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR;STROKE