Medicine/s regulators have noticed that patients with severe asthma in a previous trial had higher mortality than they expected. Based on this observation, they have commissioned us to measure the proportion of people with severe asthma who die of any cause, of infection/s, and of cardiovascular diseases including heart attacks and strokes.
We will use data from CPRD GOLD to study people with severe asthma, and then estimate how many of them die of any of the causes above. We will repeat the analysis in subgroups of different age, sex, and in different calendar years for 2015-2021.
This study will benefit the public by providing regulators with accurate information on the average mortality associated with severe asthma. This information is important because it helps understand the findings from research studies like clinical trials, where participants are selected carefully and not always representative of the general population.
Objectives
Following the observation of a higher than expected mortality in a clinical trial of severe asthma, the European Medicines Agency has commissioned the DARWIN EU centre to analyse the following:
(i) To estimate the rate of mortality in severe asthma patients stratified by calendar year, sex, and age during 2015-2021.
(ii) To estimate the rate of mortality due to fatal infections in severe asthma patients stratified by calendar year, sex, and age during 2015-2021.
(iii) To estimate the rate of mortality due to cardiovascular events in severe asthma patients stratified by calendar year, sex, and age during 2015-2021.
(iv) To estimate the incidence rate of serious cardiovascular events in severe asthma patients stratified by calendar year, sex, and age during 2015-2021.
Methods
Study design
Retrospective cohort study using CPRD GOLD data mapped to OMOP.
Population
All individuals present in the database in the period between 01/01/2015 and 31/12/2021, with at least 1 year of prior history, being diagnosed with severe asthma.
Outcomes of interest are overall mortality and cause-specific mortality and serious cardiovascular events (acute myocardial infarction, acute coronary syndrome/ischemic heart disease, stroke and hospitalisation for heart failure)
Data analyses
Annual incidence rates will be calculated stratified by calendar year, age and sex among severe asthma patients. For the calculation of incidence rates, numerator will be the patients newly diagnosed with each outcome of interest and denominator will consist of the person-years of severe asthma patients fulfilling the eligibility criteria. In addition, survival time to all-cause mortality will be estimated using Kaplan Meier analysis.
Expected benefits to patients include a more accurate evaluation of multiple medicines being studied for the treatment of severe asthma. Additionally, this research will raise awareness on the burden of severe asthma, and the need for optimal care to prevent poor health outcomes.
The following outcomes will be studied:
• All-cause mortality
• Fatal infections
• Fatal cardiovascular events
• Serious cardiovascular events (see details below).
As cause of death is not documented within CPRD GOLD, additional cohorts will be generated beside the mortality cohort. If the date of infection or cardiovascular events occurred within a window of 14 days prior to the date of mortality, cause of death will be assumed to be related to these respective conditions (i.e. mortality related to infections or mortality related to cardiovascular events)
These additional cohorts will consist of an infectious cohort (covering all types of infections) and a cardiovascular event cohort (covering all types of cardiovascular events). The concept list with SNOMED codes for these conditions of interest are described in Appendix I – Table 1: List with concept definitions.
Serious cardiovascular events are defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease, stroke and hospitalisation for heart failure. The incidence of the serious cardiovascular events as outcome will be studied overall but also by subgroup namely i) myocardial infarction - ACS/ischemic heart disease, ii) stroke and iii) hospitalisation for heart failure separately.
The concept list with SNOMED codes for these conditions of interest are described in Appendix I – Table 1: List with concept definitions.
Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Daniel Prieto-Alhambra - Corresponding Applicant - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Martí Català Sabaté - Collaborator - University of Oxford