Asthma Control, Health Care Costs, and Quality of Life
An observational study was conducted in primary care settings in France and Spain in order to estimate the societal costs and the HRQL according to the level of asthma control in adult patients.
The study design required a single visit per patient. Data collection was performed on the three-month period before the inclusion. To take into account seasonality which has a major impact on asthma in both countries, patients were recruited during a period of one year in four quarterly waves from 01/01/2010 to 12/31/2010.
The EUCOAST study was approved by the French Consultative Committee for the data processing in health research (CCTIRS) and by the National commission for the personal data protection (CNIL). In Spain, the study obtained the authorisation of the Spanish Agency of Medicines and Medical Devices (AEMPS) and the favourable opinion of the Clinical research Ethics Committee (CEIC) Hospital Clínico y Provincial de Barcelona.
Patients were included if they met the following inclusion criteria: adults aged 18 or over, diagnosed with asthma for at least 12 months and having received at least one anti-asthmatic treatment (whatever the treatment) within the past 12 months.
Exclusion criteria were participation into a clinical trial during the past 6 months, aged 45 years and over with a history of smoking of at least 20 pack years, chronic obstructive pulmonary disease (COPD) or pregnancy.
Based on the percentage of patients with controlled asthma estimated to represent 40% to 50% of the overall population in previous studies, and knowing that the size of the sample needed to estimate percentage with a ± 5% value according to the confidence interval selected (alpha risk 5%, normal distribution), around 380 patients had to be enrolled quarterly.
In France, investigators were a sample of GPs selected from a representative panel of 1,200 general practitioners. The panel's representativeness was established by three criteria: age, sex and region of practice. The study was proposed to 750 GPs of this panel, randomly selected and 230 agreed to participate.
In Spain, 105 general practitioners of 18 autonomous communities belonging to 3 regions (North, South and Mediterranean) were contacted and 87 agreed to participate. A territorial representativeness was able to be obtained when the sample was constituted.
Practitioners had to include patients in the usual context of their practice. To avoid a selection bias, the first two consecutive patients (the first five in Spain) corresponding to the inclusion/exclusion criteria visiting their doctor were included in each wave.
Data collected retrospectively (over the last 3 months) during the single study visit by the GP were: socio-demographic characteristics, medical history of patients, GINA criteria (including occurrences of exacerbations, limitations of activities, daytime and nocturnal symptoms, need of rescue/reliever treatment) and healthcare resource use due to asthma.
For all medical resources consumption (including sick leaves) during the 3 months prior to GP visit, data were provided by GPs through the questionnaires used in the study. In France some data (i.e. prescription drugs related to asthma were also collected through the computerized medical files of the GPs).
Force Expiratory Volume in one second (FEV1) was collected only in a single visit (FEV1 was measured by GPs three times consecutively as recommended by GINA). As in France and Spain, all investigators were given a digital device (Mini-Wright™ Digital, Clement Clarke International Ltd) which allowed FEV1 measurements.
At the time of the inclusion, patients completed the EQ-5D-3L® questionnaire comprising a Visual Analog Scale (VAS). This questionnaire is a generic instrument which comprises 5 dimensions: mobility, self-care, usual activity, pain/discomfort and anxiety/depression and it is widely used to assess HRQL in asthma patients. EQ-5D-3L® health states were valuated using validated French and Spanish utility value set available in each country.
In France, data were weighted to compensate the disproportion of inclusions observed among the different quarterly waves. Individual case weights were defined according to the ratio between the number of inclusions in wave 1 and the number of inclusions in the subsequent waves. In Spain, as the number of inclusions was similar in each wave, it was not necessary to weight the data.
Data analysis was performed for patients for whom lung function and symptoms of asthma were duly collected in the medical questionnaire. According to GINA 2009 criteria, patients were classified in 3 subgroups ("controlled, "partially controlled" and "uncontrolled" patients); statistic tests were performed to compare these 3 subgroups.
For categorical variables (age, gender, co-morbidities, exacerbations, smoking status, FEV1, visits, hospitalization, ambulatory exams, emergency room, drugs, sick leave), Pearson's Chi2 test or Fisher's Exact Test were applied. For continuous variables (costs, EQ-5D-3L® scores, VAS score, and number of years with a diagnosed asthma), analysis of the variance was performed. If the data were not normally distributed, non-parametric tests were used. The cost analysis was carried out according to a societal perspective and took into account both direct and indirect costs (costs associated with sick leave). Considering differences between the Spanish and the French healthcare systems, it was judged as not relevant to compare cost data across the two countries. A unit cost was given to each item according to the tariff currently used in 2010. A weighted average cost was then calculated. In France, accordingly to national guidelines, productivity loss was estimated by using the human capital method. The Gross Domestic Product for the year 2008 was divided by the number of employed population given by the "Institut National de la Statistique et des études économiques" (INSEE) for the same year. Then, the GDP per capita (employed population only) was divided by the number of working days. In Spain the average annual salary was used and sick leaves were valued by using the average annual salary divided by the number of working hours in a year (provided in Instituto Nacional de Estadística). In both case, results were multiplied by the duration of sick leaves collected through the survey.
As data were collected on a 3-month period, cost data were not discounted.
Multivariate regression analyses were performed to examine the relation between level of asthma control and the outcomes (direct costs only or HRQL levels). The costs or HRQL levels were the dependent variable and control level was the independent (explanatory) variable.
The Tobit model was used for the relation between cost and level of asthma control in order to take into account patients with zero costs (i.e., left-censoring of cost data). Multiple linear regression was used to estimate the effect associated with level of control on HRQL. The potentially confounding factors taken into account in the models were sex, age, episodes of exacerbation of asthma, prescription of a controller treatment and follow-up by a lung specialist.
Methods
Study Design
An observational study was conducted in primary care settings in France and Spain in order to estimate the societal costs and the HRQL according to the level of asthma control in adult patients.
The study design required a single visit per patient. Data collection was performed on the three-month period before the inclusion. To take into account seasonality which has a major impact on asthma in both countries, patients were recruited during a period of one year in four quarterly waves from 01/01/2010 to 12/31/2010.
The EUCOAST study was approved by the French Consultative Committee for the data processing in health research (CCTIRS) and by the National commission for the personal data protection (CNIL). In Spain, the study obtained the authorisation of the Spanish Agency of Medicines and Medical Devices (AEMPS) and the favourable opinion of the Clinical research Ethics Committee (CEIC) Hospital Clínico y Provincial de Barcelona.
Populations
Patients were included if they met the following inclusion criteria: adults aged 18 or over, diagnosed with asthma for at least 12 months and having received at least one anti-asthmatic treatment (whatever the treatment) within the past 12 months.
Exclusion criteria were participation into a clinical trial during the past 6 months, aged 45 years and over with a history of smoking of at least 20 pack years, chronic obstructive pulmonary disease (COPD) or pregnancy.
Based on the percentage of patients with controlled asthma estimated to represent 40% to 50% of the overall population in previous studies, and knowing that the size of the sample needed to estimate percentage with a ± 5% value according to the confidence interval selected (alpha risk 5%, normal distribution), around 380 patients had to be enrolled quarterly.
In France, investigators were a sample of GPs selected from a representative panel of 1,200 general practitioners. The panel's representativeness was established by three criteria: age, sex and region of practice. The study was proposed to 750 GPs of this panel, randomly selected and 230 agreed to participate.
In Spain, 105 general practitioners of 18 autonomous communities belonging to 3 regions (North, South and Mediterranean) were contacted and 87 agreed to participate. A territorial representativeness was able to be obtained when the sample was constituted.
Practitioners had to include patients in the usual context of their practice. To avoid a selection bias, the first two consecutive patients (the first five in Spain) corresponding to the inclusion/exclusion criteria visiting their doctor were included in each wave.
Data Collection
Data collected retrospectively (over the last 3 months) during the single study visit by the GP were: socio-demographic characteristics, medical history of patients, GINA criteria (including occurrences of exacerbations, limitations of activities, daytime and nocturnal symptoms, need of rescue/reliever treatment) and healthcare resource use due to asthma.
For all medical resources consumption (including sick leaves) during the 3 months prior to GP visit, data were provided by GPs through the questionnaires used in the study. In France some data (i.e. prescription drugs related to asthma were also collected through the computerized medical files of the GPs).
Force Expiratory Volume in one second (FEV1) was collected only in a single visit (FEV1 was measured by GPs three times consecutively as recommended by GINA). As in France and Spain, all investigators were given a digital device (Mini-Wright™ Digital, Clement Clarke International Ltd) which allowed FEV1 measurements.
At the time of the inclusion, patients completed the EQ-5D-3L® questionnaire comprising a Visual Analog Scale (VAS). This questionnaire is a generic instrument which comprises 5 dimensions: mobility, self-care, usual activity, pain/discomfort and anxiety/depression and it is widely used to assess HRQL in asthma patients. EQ-5D-3L® health states were valuated using validated French and Spanish utility value set available in each country.
Data Analysis
In France, data were weighted to compensate the disproportion of inclusions observed among the different quarterly waves. Individual case weights were defined according to the ratio between the number of inclusions in wave 1 and the number of inclusions in the subsequent waves. In Spain, as the number of inclusions was similar in each wave, it was not necessary to weight the data.
Data analysis was performed for patients for whom lung function and symptoms of asthma were duly collected in the medical questionnaire. According to GINA 2009 criteria, patients were classified in 3 subgroups ("controlled, "partially controlled" and "uncontrolled" patients); statistic tests were performed to compare these 3 subgroups.
For categorical variables (age, gender, co-morbidities, exacerbations, smoking status, FEV1, visits, hospitalization, ambulatory exams, emergency room, drugs, sick leave), Pearson's Chi2 test or Fisher's Exact Test were applied. For continuous variables (costs, EQ-5D-3L® scores, VAS score, and number of years with a diagnosed asthma), analysis of the variance was performed. If the data were not normally distributed, non-parametric tests were used. The cost analysis was carried out according to a societal perspective and took into account both direct and indirect costs (costs associated with sick leave). Considering differences between the Spanish and the French healthcare systems, it was judged as not relevant to compare cost data across the two countries. A unit cost was given to each item according to the tariff currently used in 2010. A weighted average cost was then calculated. In France, accordingly to national guidelines, productivity loss was estimated by using the human capital method. The Gross Domestic Product for the year 2008 was divided by the number of employed population given by the "Institut National de la Statistique et des études économiques" (INSEE) for the same year. Then, the GDP per capita (employed population only) was divided by the number of working days. In Spain the average annual salary was used and sick leaves were valued by using the average annual salary divided by the number of working hours in a year (provided in Instituto Nacional de Estadística). In both case, results were multiplied by the duration of sick leaves collected through the survey.
As data were collected on a 3-month period, cost data were not discounted.
Multivariate regression analyses were performed to examine the relation between level of asthma control and the outcomes (direct costs only or HRQL levels). The costs or HRQL levels were the dependent variable and control level was the independent (explanatory) variable.
The Tobit model was used for the relation between cost and level of asthma control in order to take into account patients with zero costs (i.e., left-censoring of cost data). Multiple linear regression was used to estimate the effect associated with level of control on HRQL. The potentially confounding factors taken into account in the models were sex, age, episodes of exacerbation of asthma, prescription of a controller treatment and follow-up by a lung specialist.
Source...