The aim of this feasibility study is to gain insights from CPRD data to better plan an appropriate trial programme consisting of randomised controlled trials investigating efficacy and safety of new treatments in development for cardiovascular disease for the benefit of patients. The trial programme is expected to be part of the submissions for regulatory approval of the study drugs.
The study population for the feasibility study will include adult persons with a history of cardiovascular disease. The study will examine how many of these persons would be eligible for inclusion in the trial programme under different eligibility criteria. The feasibility study will also assess the patient characteristics of the resulting eligible persons. These characteristics include demographics, comorbidities, medications, lipids, BMI, blood pressure, kidney and liver function, and other markers of disease. Also the feasibility study will assess the occurrence of future cardiovascular and kidney related events leading to hospitalisation as well as risk of dying and the cause of death.
Results from this feasibility study will serve as input to sample size calculations and refinement of the study designs of the trials included in the trial programme.
The overall aim of this feasibility study is to inform trial designs included in a randomised controlled trial programme investigating efficacy and safety of new treatments in development for cardiovascular disease. The trial programme is expected to be part of the submissions for regulatory approval of the study drugs. Results from this feasibility study will serve as input to sample size calculations and refinement of the study designs of the trials included in the trial programme.
Specific aims of the feasibility study include:
1) Proportion of patients eligible to participate in the trial programme under different trial population eligibility criteria. Eligibility criteria to be assessed include: atherosclerotic cardiovascular disease, heart failure, peripheral arterial disease, stroke, myocardial infarction, atrial fibrillation, chronic kidney disease, and dyslipidaemia. Crude proportions will be calculated using all patients with a history of CVD at index date as the denominator.
2) Characterisation of trial target populations with respect to baseline characteristics such as demographics, co-morbidities (chronic kidney disease, chronic obstructive pulmonary disease, osteoarthritis, diabetes), co-medications (cardiovascular drugs, glucose-lowering drugs), laboratory values (lipids, HbA1c, C reactive protein, kidney function, liver function, haematological parameters) and other clinical parameters (blood pressure, heart rate, BMI, smoking). Baseline characteristics will be analysed by simple descriptive statistics.
3) Occurrence of trial outcomes (major adverse cardiovascular events, major adverse limb events, major adverse kidney events) in target populations including relevant high-risk subgroups. Occurrence of outcomes will be calculated as crude incidence rates.
4) Incidence rates by calendar year (2005 – 2020) to serve as input to expected rates in future trials.
HES and ONS data will be used to determine CVD relevant outcomes and Practice Level Index of Multiple Deprivation data for patient characterisation. Linked data will indirectly improve patient care in England and Wales once the drugs in development become available on the market.
Major adverse cardiovascular events (composite endpoint of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death), major adverse limb events (hospitalisation due to acute or chronic limb ischemia ), Major adverse kidney events (composite endpoint of renal replacement therapy and persistent renal dysfunction), myocardial infarction, stroke, heart failure, unstable angina pectoris, atrial fibrillation, coronary artery bypass graft, percutaneous coronary intervention, peripheral revascularisation, limb amputation, kidney transplant, renal replacement therapy, persistent renal dysfunction, cardiovascular death, all-cause mortality, cause of death, hospitalisation with any cardiovascular condition, number of hospitalisations, number of days hospitalised.
Lise Lotte Nystrup Husemoen - Chief Investigator - Novo Nordisk A/S
Lise Lotte Nystrup Husemoen - Corresponding Applicant - Novo Nordisk A/S
Christian Medom Madsen - Collaborator - Novo Nordisk A/S
Irene Hedelund Langbakke - Collaborator - Novo Nordisk A/S
Mads Jeppe Tarp-Johansen - Collaborator - Novo Nordisk A/S
Thomas Jon Jensen - Collaborator - Novo Nordisk A/S
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation