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Should health-care systems pay for replacement therapy in patients with alpha(1)-antitrypsin deficiency? A critical review and cost-effectiveness analysis |
Alkins S A, O'Malley P |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Alpha1-antitrypsin (alpha1-AT) replacement therapy in individuals with severe chronic obstructive pulmonary disease (COPD) and alpha-AT deficiency. Alpha1-AT is a serum protease inhibitor that protects against neutrophil elastase in the lower respiratory tract.
Economic study type Cost-effectiveness analysis.
Study population Patients with severe COPD and severe alpha1-AT deficiency, and who are PiZZ homozygous and have a FEV1 less than 50% of predicted.
Dates to which data relate The effectiveness data were extracted from articles published in the period 1980-1998. The resources were estimated using reimbursement data and were reported in 1998 values.
Source of effectiveness data The effectiveness data were derived from a review/synthesis of the literature.
Outcomes assessed in the review The outcomes assessed were mortality rates, namely absolute risk reductions in mortality between treated and untreated groups.
Study designs and other criteria for inclusion in the review Randomised controlled trials (RCTs) and observational studies were included in the review.
Sources searched to identify primary studies The electronic databases MEDLINE and EMBASE (between 1980 and 1998) and the bibliographies of relevant articles were searched. The following search terms were used: alpha1-antitrypsin deficiency, alpha1-antitrypsin replacement therapy, efficacy, cost-effectiveness, mortality, therapeutic use, pharmacokinetics, administration, and dosage.
Criteria used to ensure the validity of primary studies The authors stated that the conventional hierarchy of best designed and least biased evidence was used to ensure the validity of the primary studies.
Methods used to judge relevance and validity, and for extracting data The methods used were not reported.
Number of primary studies included Only one study retrieved met the inclusion criteria and this was held in the National Institute of Health Registry. Other studies were located but these did not report mortality rates.
Methods of combining primary studies Not applicable as only one study was used from the review.
Investigation of differences between primary studies Not applicable as only one study was used from the review.
Results of the review The 5-year mortality rate in those subjects with an initial FEV1 less than 50% was reduced by 55% through the use of alpha1-AT replacement therapy (tested between 5% and 70% in the sensitivity analysis).
Measure of benefits used in the economic analysis Life-years gained were calculated as the difference in life expectancy in treated patients minus that of untreated individuals. Benefits were discounted in the range 0% to 7%. Life expectancy was calculated using the declining exponential approximation of life expectancy.
Direct costs The costs for IV human alpha1-AT replacement therapy were calculated from a payer perspective based on Medicare and were reported in 1998 US dollars. The quantities and cost of the medication were reported separately. Overhead costs were not considered since they were not included in Medicare reimbursement payments. Discounting was not reported. Costs were calculated on the basis of a 1-hour 60 mg/kg/week IV treatment schedule. The price year was 1998.
Indirect Costs No indirect costs were reported.
Sensitivity analysis To assess the robustness of the findings, sensitivity analyses were performed. Several important variables were simultaneously varied to test whether the cost-effectiveness was sensitive to any variable. The effect size (5-year risk in treated individuals versus 5-year risk in untreated individuals) was varied from 5% to 70% to account for the uncertainty associated with using data from an observational study. Cost was varied up to 500% of the Medicare part B reimbursement. to allow for differences in expenses. Years of life saved were discounted to account for the decrease in quality of life associated with weekly infusions. The discount rate for benefits was varied between 0% and 7%. The end points selected for the sensitivity analysis were chosen as reasonable extreme estimates beyond which any cost and effectiveness that were calculated would be unlikely.
Estimated benefits used in the economic analysis The incremental life-years gained were not reported. The 5-year mortality rate was reduced by 55% by the intervention in the base case scenario.
Cost results In the base case scenario the yearly total cost would be $51,498, and the five year total cost would be approximately $260,000.
Synthesis of costs and benefits The incremental cost per year of life saved in the base-case scenario was found to be $13,971 (calculated assuming a 55% 5-year mortality reduction without discounting the years of life saved). The results of the sensitivity analyses showed that if yearly costs were unchanged but the effect size was 10%, the incremental cost would be $152,941. If the effect size was assumed to be 70%, then the incremental cost would be $7,330. If the yearly cost was assumed to increase by nearly 300% to $150,000 and the effect size was taken to be 55%, then the incremental cost would be $40,301. The incremental analysis was compared to cost-effective thresholds to give context to the findings: at an annual cost of $40,000 for renal dialysis per year saved, the effect size of the replacement therapy should be greater than 30% for the intervention to be considered cost-effective.
Authors' conclusions Human alpha-1 replacement is safe and appears to retard the accelerated decline of FEV1 and overall mortality rate in a distinct subset of individuals (those who are PiZZ homozygous and severely alpha-1 antitrypsin deficient, with an initial FEV1 less than 50% of predicted). Lifelong augmentation therapy in these selected individuals is cost-effective by currently accepted standards.
CRD COMMENTARY - Selection of comparators The authors' choice of usual care as a comparator was justified. This assumed that the standard interventions for usual care (bronchodilators or smoking cessation efforts for instance) were also used with individuals receiving the intervention.
Validity of estimate of measure of benefit The effectiveness data were derived from what may have been a systematic review of the literature. However, the highest level of evidence produced by the literature search was one study that included mortality outcomes. This observational study was used in the absence of RCTs and may have limited validity, as this form of research is well down the hierarchy of clinical evidence according to well accepted criteria. This limitation (only one study) was minimised, however, by conducting extensive sensitivity analyses.
Validity of estimate of costs All relevant direct costs appear to have been included. The validity of the estimate appears to be quite high and an extensive sensitivity analysis was carried out to address the limitations in the data. A third payer perspective was considered and indirect costs were not included which limits the generalisability of the results to other settings or healthcare systems.
Other issues The authors did make appropriate comparisons of their findings with those from other studies, and their findings are similar to those of other authors. The controversy regarding the interpretation of the available studies of alpha1-AT replacement therapy is demonstrated by the different recommendations of the Canadian and America Thoracic Societies. The issue of generalisability to other settings was not completely addressed, and more effectiveness data would be required for further validation of the results. The authors did not address the discounting of costs or quality of life changes due to the replacement therapy.
Implications of the study The results suggest that lifelong augmentation with alpha1-AT for selected patients is cost-effective according to current standards. More effectiveness data, however, would ideally be needed, but the authors note that a randomized controlled trial may be unethical or too costly to justify based on the already available data.
Bibliographic details Alkins S A, O'Malley P. Should health-care systems pay for replacement therapy in patients with alpha(1)-antitrypsin deficiency? A critical review and cost-effectiveness analysis. Chest 2000; 117(3): 875-880 Indexing Status Subject indexing assigned by NLM MeSH Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Insurance Coverage /economics; Lung Diseases, Obstructive /drug therapy /economics /mortality; Medicare /economics; Reimbursement Mechanisms /economics; Survival Analysis; United States; Value of Life; alpha 1-Antitrypsin /economics /therapeutic use; alpha 1-Antitrypsin Deficiency /drug therapy /economics /mortality AccessionNumber 22000000652 Date bibliographic record published 30/06/2001 Date abstract record published 30/06/2001 |
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