Should Health-Care Systems Pay for Replacement Therapy in Patients With Alpha1-Antitrypsin Deficiency? A Critical Review and Cost-Effectiveness Analysis

Stephan A. Alkins, MD and Patrick O'Malley, MD, MPH From the Pulmonary and Critical Care Medicine Service (Dr. Alkins) and the Department of Internal Medicine (Dr. O'Malley), Walter Reed Army Medical Center, Washington, DC.


CHEST. 2000;117(3) 

In This Article

Materials and Methods

We searched the electronic databases MEDLINE and EMBASE between 1980 and December 1998 using the following terms: alpha 1-antitrypsin deficiency, alpha 1-antitrypsin replacement therapy, efficacy, cost-effectiveness, mortality, therapeutic use, pharmacokinetics, administration, and dosage. Bibliographies of relevant articles also were reviewed.

The effect size for the economic analysis was taken from the study with the highest level of supporting evidence that included the mortality outcomes, according to the conventional hierarchy of best designed and least biased evidence.[11,12] Effect size was defined as the absolute risk difference between treated and untreated groups. The National Institutes of Health (NIH) Registry was solely utilized in this analysis because it contained the only study identified that included mortality outcomes.[10] Other reports document only the change in FEV1 between treated or untreated groups.[7,8,9]

Life expectancy (LE) was calculated using the declining exponential approximation of life expectancy.[13,14] LE was defined as the inverse of mortality (1/m). Mortality was calculated by -(1/t) x ln(survival over time), where t is time, ln is the natural log, and survival is the percentage of subjects alive over time t. Years of life saved was calculated as the LE of treated individuals (LEtreated) minus that of untreated individuals (LEuntreated).

The costs for IV human alpha1-AT (Prolastin; Bayer, Inc; West Haven, CT) replacement therapy are calculated from a payer perspective based on Medicare part B reimbursement rates and are reported in 1998 US dollars. This perspective was chosen since Medicare reimbursement is becoming the standard on which health-care delivery systems are basing their reimbursement decision making. The cost estimates were as follows, assuming a weekly 1-h infusion at 60 mg/kg IV. The medication cost is $105 per 500 mg alpha1-antitrypsin, and a 70-kg patient would require nine 500-mg vials of alpha1-antitrypsin each week. A 1-h infusion of medication can be reimbursed at $54 for the first hour; therefore, a 1-h infusion of 60 mg/kg in a 70-kg patient would cost $945 for alpha1-antitrypsin and $54 for the infusion. The yearly total cost would be $51,948, and the 5-year total cost would be approximately $260,000. The optimal timing and dosage of alpha1-AT replacement therapy was based on the most recent guidelines issued by the American Thoracic Society, which recommend that alpha1-antitrypsin be administered weekly at a dose of 60 mg/kg/wk.[15] Overhead costs were not considered since these are not included in Medicare reimbursement payments.

To assess the robustness of our findings, we performed a sensitivity analysis. Several important variables were varied simultaneously to test whether the cost effectiveness was sensitive to a quantity of any variable. The effect size (in this case, absolute risk difference [5-year risk in treated individuals vs. 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. The cost was varied up to 500% of the Medicare part B reimbursement rates to allow for differences in expenses. The increase in years of life saved by augmentation therapy was compared with and without discount. The years of life saved were discounted to account for the decrease in quality of life associated with weekly infusions. The discount rate was varied between 0% and 7%, as previously described by Weinstein et al.[16] This rate was used to account for variables that might affect the validity of the outcomes benefit used in this analysis (health system costs introduced through patient survival and potential costs from therapy complications, for example).[17] The sensitivity end points were chosen as reasonably extreme estimates beyond which any costs and effectiveness that are calculated would be unlikely.

Comparisons were made to usual care. This assumed that standard interventions for usual care (bronchodilators or smoking cessation efforts, for instance) also were used in those individuals receiving the intervention. Thus, cost is presented as the incremental cost (or value added) associated with the intervention.[18]


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