The Programme for control of asthma and Allergic Rhinitis in Bahia (ProAR)
This programme was organized by Federal University of Bahia Medical School and obtained operational support from the Unified Health Service (in Salvador, a unified public health system, comprising the Department of Health of the City of Salvador, the Department of Health of the State of Bahia and Brazilian Ministry of Health [11]). ProAR aims were to reduce symptoms and prevent exacerbations in severe asthmatics, with an integrated approach by a team of chest physicians, allergists, pediatricians, nurses, pharmacists, social workers and psychologists. Asthma education sessions are offered to patients and family members. Inhaled corticosteroids (budesonide) combined with long acting bronchodilators (formoterol) are given with no cost to all patients, as recommended by Global Initiative for Asthma (GINA) guidelines [12]. Nasal topical corticosteroids are also given to those with concomitant chronic rhinitis. ProAR started recruiting patients with severe asthma in Salvador in 2003; by October 2006, 1796 patients had been recruited into the programme.
Participants
Eighty-one patients with severe asthma, from 12 to 75 years old, living in Salvador and its metropolitan area, were consecutively selected from those attending regularly the referral clinic for ProAR. To be included in the study, patients were required to have more than one year of severe asthma according to the classification by the Global Initiative for Asthma [12]. Therefore, the patients typically had continuous asthma symptoms, as well as daily limitation to exercise, frequent exacerbations and night symptoms, requiring daily use of a bronchodilator. The majority reported frequent emergency visits, hospitalizations, and some had been admitted to intensive care units. They also had a low forced expiratory volume in one second (FEV1) on spirometry. Additionally, patients were required to have no contraindications for the use of the inhaled corticosteroids and/or long acting beta 2 agonists bronchodilators, no concomitant lung disease (as assessed by history and chest X-Ray); to be non-smokers or have a smoking history < 10 pack/years and be capable of giving written informed consent. Recruitment was limited by convenience to patients admitted to the programme between April and September of 2004.
Study design and evaluation procedures
This is a "before and after study" (pre-post study) of 81 patients with severe asthma, managed in ProAR. The objective was to compare the cost-effectiveness, for families and the public health system, of two strategies for severe asthma management of the same patients: the regular asthma care available in the Salvador public health system they used before joining ProAR and that offered by ProAR. The analysis considered the management of asthma one year before and one year after admission to ProAR.
Figure 1 summarizes the chronology of the study procedures. Upon referral to the programme, the selected patients were invited to participate in this study, to sign an informed consent form, and to answer the AQLQ (Asthma Quality of Life Questionnaire) and the ACQ (Asthma Control Questionnaire) that are standard instruments to measure asthma control and asthma-specific quality of life, both of which had previously undergone linguistic validation to Portuguese and are available electronically [13–16]. A month later they had their first medical consultation in ProAR, when they were seen by a specialist and received free medication. Both ACQ and AQLQ questionnaires were repeated during this visit. Afterwards, the ACQ and AQLQ questionnaires were answered every 3 months during the one-year of follow up. The two initial repeated questionnaire scores one month apart were taken as the patients' baseline status of asthma control and quality of life before intervention. During the initial visit researchers collected economic and clinical retrospective information regarding asthma treatment in the past 12 months, including patient's and family's income, expenses with transportation, doctor's visits, medications, therapeutical devices and diagnostic tests, emergency room visits, hospitalizations and intensive care admissions due to asthma. The same information was then collected prospectively on monthly visits during ProAR follow up and intervention for one year, for comparison with the previous year. Patients performed lung function tests to obtain forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEF) at baseline, before joining ProAR, and at 6 and 12 months of follow up to objectively evaluate their asthma control status [17]. The Ethics Committee of Human Research – School of Medicine of Federal University of Bahia, approved the study.
The economic analysis
In order to compare the cost-effectiveness of treatment of severe asthma for the two strategies (regular public health system care and the ProAR), the costs for the public health system, for ProAR and for the families were estimated using accounting procedures. All these costs have been brought up to values at the time of the main analysis (February 2006) and the necessary depreciation estimated.
Costs were estimated for the public health system and for ProAR: health related direct costs for each patient, before and after their inclusion on the programme. The costs of outpatient care within the year before intervention, comprising doctor's visits, medications and diagnostic tests were calculated based on patient' retrospective information and using government official reimbursement values and pharmaceutical retail price. The costs of hospitalization, emergency room visits, and intensive care unit admissions, both after and before joining ProAR, were estimated based in Health Department of State of Bahia databases and public and charity hospitals' financial department surveys. To estimate the average cost of a day of hospitalization for a case of asthma we took into account the average total direct costs with hostelry (staff, current expenses, equipment and facilities depreciation, office and medical supplies), the number of total patients and the proportion of patients with asthma hospitalized per year, and the costs of specific asthma medication. The costs of ambulatory health care in ProAR were estimated as follows: the total annual stable costs with current regular expenses (administration, water supply and energy consumption, security, cleaning, maintenance), office and medical supplies, communications and staff, divided by the total number of patients admitted, to obtain the cost per patient/year. The variable costs were estimated by analyzing individual expenses with diagnosis and treatment.
Family costs- family's direct and indirect costs were estimated by using the Asthma Family's Costs Questionnaire (AFCQ), which collects information on the costs incurred by the families due to asthma treatment of a family member. This was adapted from a questionnaire previously created to estimate family costs of tuberculosis in Brazil [18]. The AFCQ reliability and reproducibility were evaluated and confirmed in asthma among 30 patients of our programme. The AFCQ is available electronically [19] and detailed results of its validation have been a matter of a paper that has been submitted to publication. This instrument has 33 questions divided into sets of items: family income, financial help, transportation expenses, loss of job, school absence due to asthma, medicines purchase, other expenses and loss of time waiting or moving to health services. The questionnaire was applied at baseline, to quantify expenses over the year before patient's admission to ProAR, and again at the end of study, to measure costs to the family during the year of ProAR intervention.
Cost-effectiveness analysis - the analysis was conducted to compare two treatment strategies for severe asthma. The first one is the regular treatment offered by the public health system in Salvador, in which patients received treatment only to control exacerbations with no regular inhaled or oral preventive medications or regular follow up. The second approach, in the same patients, after admission to ProAR and being followed prospectively for one year receiving multiprofessional regular care, free inhaled preventive medication and educational sessions. The effectiveness of the intervention was measured as "hospitalizations avoided" by the programme. Cost-effectiveness incremental analysis was performed by comparing the costs and health results, dividing the difference in costs per the difference of health results obtained on each strategy [20].
Sensitivity analysis – this was carried out to ascertain the reliability of the cost-effectiveness analysis under varied assumptions regarding costs of health care. We challenged our main findings by repeating the cost-effectiveness analysis while changing the estimated hospitalization cost from our real life calculus to what was reimbursed to the State or City Departments from the Ministry of Health, which was 76% less [21].
Statistical analysis
The sample size was calculated by Stats Direct 7.0 software considering the estimated ProAR intervention effect of reducing hospitalizations during one year, as compared to the year before. Hospitalizations are an important parameter to assess asthma control, morbidity and costs [12]. The minimum sample size required to detect as statistically significant a 50% reduction in costs per patient/year was 58 patients, for a power of 80%. We increased the sample to 81 patients in order to compensate for probable losses of follow up or mortality of patients with such severe disease.
Data were entered onto a Microsoft Excel® and SPSS 11.5 spreadsheet for statistical analysis. Two tailed tests were carried out and p values lower than 0.05 considered statistically significant. The categorical variables were reported as proportions and compared with Chi-square Tests. All continuous variables were compared by using Wilcoxon Signed Rank Test [22].