Medical Literature Evaluation

Introduction

Title: Costs and Effects of Inhaled Corticosteroids and Bronchodilators in Asthma and Chronic Pulmonary Obstructive Disease.

Authors: Maureen Rutten Van Molken, Eddy Van Donslaer, Margreet Jansen and Frans Ruttten.

Funding: Department of Health Economics, University of Limburg, Maastricht the Netherlands; Institute of Medical Technology Assessment, Erasmus University Rotterdam, the Netherlands; Department of Pulmonology, University Hospital Groningen, the Netherlands.

Objective: “Determination of the cost and effects of combined bronchodilator and anti-inflammatory therapy.”

Background

• Recent epidemiological and economical publications have documented that the cost of health care utilization due to asthma in the United States exceeded $3.6 billion in 1990. In Netherlands the cost of asthma and or chronic obstructive pulmonary disease (COPD) exceeded $0.5 billion in 1985.
• The primary treatment approach is pharmacotherapy which is very costly. In the United States asthma accounts for more than 30% of total expenditure on pharmacotherapy while in Netherlands more than 7% of the total drug sales are related to asthma or COPD.
• This realization provided the need to evaluate the cost effectiveness of therapy and treatment related to COPD and asthma.
• No economic evaluation study has managed to address the long term effects of respiratory drugs.

Methods

Design: Economic analysis in conjunction with a double blind study.

Setting: Six university pulmonary outpatient in Netherlands.

Sample Population: 274 patients aged between 18 and 60 years with obstructive airway disease who exhibited both airway obstruction and hyper responsiveness. Airway obstruction was defined as FEV₁ (Forced Expiratory Volume in one second) or FEV₁/FVC (Forced Vital Capacity) below the 95% confidence interval normality. Hyper responsiveness was defined by the concentration that caused a 20% fall in FEV₁ (PC₂₀).

Inclusion Criteria

Case Patients: patients were required to discontinue the use of inhaled corticosteroids at least 4 weeks before randomization. Patients were then assigned to one of the three drug regimens. (1)BA + CS: an inhaled beta 2 agonist combined with an inhaled corticosteroid, (2) BA + AC: an inhaled beta 2 agonist combined with an inhaled anticholinogernic, (3) BA + PL: an inhaled beta 2 agonist combined with a placebo

Control Subjects

Exclusion Criteria: Serious concomitant disease or usage of drugs that may interfere with the study.

Outcome Measures

Primary

Clinical End-points: FEV₁ % was used to predict the obstruction of the airway while histamine was used to predict the responsiveness. This measures were performed when patients were clinically stable and not within the 4 week period after termination of prednisolone course. “Wheezing, coughing, shortness of breath, and mucous secretion was measured on a four point scale.” The information was extrapolated to 3 months.

Economical End-points: The cost if health care utilization was calculated in consideration of the study drugs, prednisolone rescue therapy, antibiotics rescue therapy, inhaled salbutamol rescue therapy and any additional drug related to asthma or COPD.

Secondary

The relationship between the use of asthma and COPD medication and the cost of the medication.

Statistical Analysis

A complete intention to treat analysis was not available due to absence of data. For the patients who completed the study and those who did not, the mean cost per patient in a year was obtained by dividing each patient’s total health care cost by the number of quarters the patient was in trial. This was in turn multiplied by 4. In analysis of the two combinational therapies BA + PL, calculations were done using base 2 logarithmic of PC₂₀ to account for the double concentration. Z-test was used to test differences in withdrawal rates while T-test was used for restricted activity and symptom free days.

Results

Subjects

Two hundred and seventy four patients were assigned to one of the three treatment groups (BA + CS, BA + AC and BA + PL). The difference between BA + CS, BA + AC and BA + PL was not statistically significant. The number of symptom free days per patient per year was found to be 121 in BA + CS group as compare to 84 in the BA + PL and 68 in BA + AC. The mean (SE) difference 37.5 (17.8) d between BA + CS and BA + PL was statistically significant (p=0.032).

Outcomes

The annual drug acquisition cost was of combined BA and CS therapy was found to be 532 $US per patient. This was 376 $ US more than BA and PL. The annual drug cost for BA + CS and BA + PL were 277 $US and 156 $US respectively. To reduce the skewness costs were logarithmically transformed. The incremental cost effectiveness ratio of combined BA and CS therapy was calculated as the ratio of the cost difference between BA + CS and BA + PL to the difference in effects parameters between BA + CS and BA + PL. The incremental cost effectiveness ration was found to be 200 $US for every 10% increase in FEV₁, with an approximation of 95% confidence limit ranging from 57 $US to 450 $US. With all the other factors constant BA + CS therapy had lower cost as compared to BA + PL therapy. Furthermore, patients with higher FEV₁ also had lower care costs as compared to patients with lower FEV_1.

Discussion

The study established that the addition of inhaled corticosteroids for patients with moderately severe obstructive airways with beta agonist results in a small but significant net increase in health cost by about 201 $US per patient.

Strengths Noted by Authors

1. BA + CS therapy was more beneficial compared with bronchodilator monotherapy.
2. The study also provided a comparison between the two different therapies apart from just looking at their cost effectiveness.
3. Various other variables such as life style of the patients were also put into consideration to account for their contribution.

Limitations Noted by Authors

1. The study fails to address the more important issue of resource allocation.

Authors Postulated explanation of the results.

2. BA + CS therapy raised FEV₁ thereby reducing the cost of care.
3. BA + PL therapy lowered FEV₁hence increasing cost of care.

My Evaluation

Strengths of the Study.

1. The use of six outpatient university facilities increased the probability of getting correct results due to the large coverage.
2. The study was significant in that it addresses the economic impact of specific pharmacotherapy.
3. The authors were able to document each step and the challenges they faced together with the strengths and weaknesses of the study.

Weaknesses of the Study

1. There are other variables that the patients might have failed to reveal conclusively. Such variables could have altered the results.
2. The use of COPD and asthma seemed to have been too generalized. Perhaps they could have been addressed via independent studies.
3. The parameters used to analyse the symptoms might have been contributed by other factors apart from COPD and asthma.

Applicability of the study

The research will be helpful in determining the most appropriate and cost effective form of treatment for COPD and asthma. The research may also be a starting point for further studied that may want to look into budgetary allocation on various therapies.

Reference

Rutten-Van Mölken et al. (1995). Costs and Effects of Corticosteroids and Bronchodilators in Asthma and Chronic Obstructive Disease. American Journal of Respiratory and Critical Care Medicine, 151. Web.