EMPOWER-1: A Multi-site Clinical Cohort Research Study to Reduce Health Inequality

Study Overview
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Brief Summary
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Health inequality and genetic disparity are a significant issue in the United Kingdom (UK). This study focuses on diseases that are associated with significant morbidity and mortality in the UK, and specifically examines the extent and basis of treatment failure in different patient populations. The vast majority of drug registration clinical trials have under-representation of ethnic minority populations. In addition, the wider Caucasian populations have reasonably different clinical characteristics to the population that participated in the drug licencing clinical trials. A consequence of this is that drugs are licensed for use in real-world general patient populations where the clinical trial results are simply not statistically significant to specifically demonstrate efficacy or safety in populations that were either absent or under-represented in the drug registration clinical trials. When these facts are considered alongside data that supports significant under-reporting of adverse events in the real-world setting within the UK (and globally, e.g the USA and Europe), it highlights that pharmacovigilance systems are unable to capture drug effectiveness and safety data in a manner that can reasonably assure appropriate prescribing in the wider patient populations. This large real-world research study aims to identify whether commonly prescribed drugs are effective in treating illnesses that cause significant poor health and death in the different patient populations that represent the UK. The goal of this study is to generate large quantitative data-sets that may inform clinical practice to reduce the existing health inequality and genetic disparity in the UK.

Detailed Description
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This multi-centre real-world study will recruit patients across different National Health Service (NHS) sites based in England, where the overall patient population demographic profile is sufficiently variable to allow for meaningful representation of different ethnicities in the analysis of pooled data-sets. The study addresses the issue of health inequality and genetic disparity in the United Kingdom (UK) by recruiting up to 200,000 patients primarily from the three main ethnic groups in the UK; namely White (Caucasian), African-Caribbean (Black), and South Asian (Asian) populations on a 1:1:1 ratio. Biological samples, medical records, alongside specific questionnaires will be used in data analyses to help identify treatment failures in different populations for the 19 disease areas under investigation, which are a significant cause of morbidity and mortality in the UK. Analysis of patient populations may provide real-world evidence around disease prevalence between and within different ethnic groups. The data may also support hypothesis driven genetic analysis to identify putative bio-markers associated with treatment failure. Data from this study will be published, and findings could better inform clinical practice in the management of diseases that cause significant poor health and death in the different populations that represent the UK.

Official Title
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EMPOWER-1: A Multi-site Clinical Cohort Study to Reduce Health Inequality: Identifying Ethnic Disparities in Treatment Failures for Medicines Prescribed to Treat Diseases That Cause Significant Mortality and Morbidity in the UK Population

Conditions
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Atrial Fibrillation, Coronary Heart Disease, Cardiovascular Diseases, Heart Failure, Hypertension, Peripheral Arterial Disease, Stroke, Ischemic, Asthma, Chronic Obstructive Pulmonary Disease, Obesity, Cancer, Chronic Kidney Diseases, Diabetes Mellitus, Dementia, Depression, Epilepsy, Mental Health Disorder, Rheumatoid Arthritis, Blood Pressure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients or their relative/family member is diagnosed with the illness being investigated by this study. All NHS patients that are associated with a participating study site, but do not fall under the first bullet point above, may participate with a view that they may potentially contribute to a case control population in the research study. Subjects agree to: Gift biological samples, i.e. saliva. Where practical, blood or other biological samples may be voluntarily provided by the patient. Provide Consent for access to medical records. Complete disease specific, quality of life, and study associated questionnaires. Exclusion Criteria: Patient does not provide a valid consent for study participation. Patient is not registered with the NHS for care. Patient lacking capacity, who does not have an illness that is being specifically investigated by this clinical research study. Person lacks capacity and where the personal consultee has not advised that the Person may enrol, in accordance with the Mental Health Act 2005.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Displaying trait of interest<br>There are 19 disease areas under investigation. Enrolled patients are segmented into cohorts based on data collected through questionnaires and medical histories. This data-driven approach does not allow for precisely predefined cohorts for the diseases under investigation. Therefore, as a default, the two general predefined cohorts are set as either displaying or not displaying a trait that would form the basis of an investigation. | |
| Not displaying trait of interest<br>Please see above. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ethnic disparities in treatment failure | Identify ethnic disparities in treatment failures for any of the 19 disease states under investigation. The primary outcome is treatment failure, as measured by the discontinuation of a treatment regimen by a clinician in the absence of the cure of the disease, for the most common treatment in each of the 19 diseases. | Ongoing review of data, anticipated completion of primary outcome analysis 4 years post launch | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ethnic disparities in disease incidence | Identifying ethnic disparities in disease incidence. The corresponding secondary outcome measure for this is, for each of the 19 diseases under consideration, the diagnosis of the disease. We will use time to diagnosis to examine ethnic disparities in incidence. | Ongoing review of data, anticipated completion of analysis 5 years post launch | 
| Identification of candidate genetic variants associated with observed disparities in treatment failure. | Another secondary outcome is identifying candidate genetic variants that may underpin observed disparities in treatment failure, for treatments in the 19 diseases under consideration. The corresponding secondary outcome measures used for this are genotypes as identified through whole genome sequencing (WGS) of patient saliva or peripheral blood that are associated with the phenotypes corresponding to the treatment failure previously described as the primary outcome measure. | Ongoing review of data, anticipated completion of analysis 5 years post launch | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genetic disparity, health inequality, genetics, health outcomes, equality