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Local treatment pattern versus trial-based data: a cost-effectiveness analysis of drotrecogin alfa (activated) in the treatment of severe sepsis in Sweden |
Hjelmgren J, Persson U, Tennvall G R |
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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 The study compared the use of drotrecogin alfa (activated) as an adjunct to standard therapy with standard therapy alone.
Economic study type Cost-utility analysis and cost-effectiveness analysis.
Study population The study population comprised patients with severe sepsis.
Setting The study setting was secondary care. The economic study was carried out in Sweden.
Dates to which data relate The effectiveness data were derived from a study published in 2001. The price year was 2002.
Source of effectiveness data The effectiveness data were derived from the PROWESS trial (Bernard et al. 2001, see 'Other Publications of Related Interest' below for bibliographic details).
Link between effectiveness and cost data Since no Swedish patients were included in the PROWESS trial, the authors collected resource use information from a patient population treated at Huddinge University Hospital in Sweden. Resource use information was derived from a total of 55 patients with both a septicaemia infection and at least one acute organ dysfunction diagnosis, of which 17 (31%) had two or more diagnoses of organ dysfunction.
Study sample The authors provided very few details of the PROWESS trial. Further information can be obtained elsewhere (Bernard et al. 2001). The PROWESS trial included 1,690 patients, the mean age of these patients being 60.5 (standard deviation 17.7) years.
Study design The authors provided very few details of the PROWESS trial. Further information can be obtained elsewhere (Bernard et al. 2001). The PROWESS trial was a randomised, double-blind, placebo-controlled, Phase 3 study.
Analysis of effectiveness The authors provided very few details of the PROWESS trial. Further information can be obtained elsewhere (Bernard et al. 2001). The PROWESS trial assessed all-cause mortality at day 28.
Effectiveness results The authors provided very few details of the PROWESS trial. Further information can be obtained elsewhere (Bernard et al. 2001).
The PROWESS trial found significant reductions in all-cause mortality at day 28.
In all patients included in the trial, the reduction in absolute risk was 6.1% while the risk reduction was even higher, 7.4% in a sub-group of patients with two or more organ dysfunctions.
Clinical conclusions The PROWESS trial found significant reductions in all-cause mortality at day 28.
Modelling The authors used a model based on the PROWESS trial that had been developed to estimate the cost-effectiveness of drotrecogin alfa (activated). The authors, however, adjusted the model to take treatment practice in Sweden into consideration. Three different methodological approaches were applied in the model.
In the "local data approach", the original model was adjusted with Swedish data on prices, resource use, patterns of care, age and gender structure of patients with severe sepsis treated in the intensive care unit, and life tables.
In the "local unit price approach", the model based on PROWESS trial data was adjusted with Swedish prices only.
The third approach used a combination of data from the two other methods.
In all cases, clinical outcome and study drug were obtained from PROWESS data.
Measure of benefits used in the economic analysis The measures of benefits used were the life-years gained (LYG) and the quality-adjusted life-years (QALYs) gained. To estimate the number of LYG, the absolute risk reduction observed in the PROWESS trial was multiplied by the life expectancy according to Swedish life tables of patients surviving at 28 days. Based on results from the literature, life expectancy was multiplied by a weight of 0.5 to adjust for the common existence of simultaneous co-morbidity in patients with severe sepsis. The QALYs were then generated by applying a utility weight of 0.69, again derived from the literature, to all survivors of severe sepsis at 180 days from admission and over their expected remaining lifetime. All future benefits were discounted at an annual rate of 3%.
Direct costs The direct costs of the health care provider were included in the analysis. These were for drotrecogin alfa (activated), intensive care, and hospitalisation in a general ward. The cost of drotrecogin alfa (activated) was based on the 2002 Swedish price. The total hospital costs for the drotrecogin alfa (activated) treatment arm were calculated on the basis of hospital costs for patients with severe sepsis treated at Huddinge Hospital multiplied by the relation between the number of inpatient days in the trial for patients treated with drotrecogin alfa (activated) and standard care. Since the costs were incurred during a short period of hospitalisation, discounting was not relevant and was therefore not performed. The study reported the average costs. The price year was 2002.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs The indirect costs were not included.
Sensitivity analysis The authors performed one-way sensitivity analyses by varying the absolute risk reduction in mortality and the drug price by 10% each way. The effect of the discount rate was also assessed by varying it from 0 to 5%.
Estimated benefits used in the economic analysis Using the local data approach, the total additional QALYs gained for patients treated with drotrecogin alfa (activated) as opposed to standard care were 0.375 (0.544 LYG) for patients with one or more organ dysfunctions and 0.327 (0.474 LYG) for those with two or more organ dysfunctions.
Using the local unit price and local data-trial age structure approaches, the total additional QALYs gained for patients treated with drotrecogin alfa (activated) as opposed to standard care were 0.313 (0.453 LYG) for patients with one or more organ dysfunctions and 0.470 (0.680 LYG) for those with two or more organ dysfunctions.
Cost results Using the local data approach, the total incremental hospital cost for patients treated with drotrecogin alfa (activated) as opposed to standard care was EUR 9,701 for patients with one or more organ dysfunctions and EUR 11,591 for those with two or more organ dysfunctions.
Using the local unit price approach, the total incremental hospital cost for patients treated with drotrecogin alfa (activated) as opposed to standard care was EUR 9,771 for patients with one or more organ dysfunctions and EUR 10,885 for those with two or more organ dysfunctions.
Using the local data-trial age structure approach, the total incremental hospital cost for patients treated with drotrecogin alfa (activated) as opposed to standard care was EUR 9,701 for patients with one or more organ dysfunctions and EUR 11,591 for those with two or more organ dysfunctions.
Synthesis of costs and benefits The costs and benefits were combined using an incremental cost-effectiveness ratio (ICER; i.e. the additional cost per additional LYG when drotrecogin alfa was compared with standard care) and an incremental cost-utility ratio (ICUR; i.e. the additional cost per QALY gained).
Using the local data approach, the ICUR was EUR 26,232 (ICER: EUR 18,126) for patients with one or more organ dysfunctions and EUR 35,124 (ICER: EUR 24,400) for patients with two or more organ dysfunctions.
Using the local unit price approach, the ICUR was EUR 31,241 (ICER: EUR 24,556) for patients with one or more organ dysfunctions and EUR 23,138 (ICER: EUR 15,965) for patients with two or more organ dysfunctions.
Using the local data-trial age structure approach, the ICUR was EUR 31,016 (ICER: EUR 21,401) for patients with one or more organ dysfunctions and EUR 24,661 (ICER: EUR 16,410) for patients with two or more organ dysfunctions.
The sensitivity analysis showed that the results obtained in the base-case were rather insensitive to minor changes in treatment effect and the drug price, but were more sensitive to changes in the discount rate.
Authors' conclusions Drotrecogin alfa (activated) was a cost-effective alternative for the treatment of Swedish patients with severe sepsis and organ dysfunction, irrespective of the approach used in the cost-effectiveness analysis.
CRD COMMENTARY - Selection of comparators The authors correctly compared drotrecogin alfa (activated) with standard care in the treatment of severe sepsis and organ dysfunction. However, the authors did not provide any details of what standard care represented in their setting.
Validity of estimate of measure of effectiveness The effectiveness data were derived from a large randomised, double-blind, placebo-controlled trial. Although the authors reported very few details of this trial, it would appear that the trial was a well-conducted, randomised controlled trial with internally valid results. Further, the authors undertook a sensitivity analysis by varying the treatment effect.
Validity of estimate of measure of benefit The estimation of benefits was modelled using data from the PROWESS trial, Swedish life tables and utility estimates derived from the literature. As the benefits could be incurred over the lifetime of the patient, all future benefits were appropriately discounted.
Validity of estimate of costs All the categories of cost relevant to the hospital perspective adopted were included in the analysis. No major costs appear to have been omitted from the analysis. The costs and the quantities were reported separately for some categories, which will enhance the generalisability of the authors' results. Since no Swedish patients were included in the PROWESS trial, the authors collected resource use information from a patient population treated at Huddinge University Hospital in Sweden. The unit costs were derived from this same institution. The authors performed a very limited sensitivity analysis by varying the unit cost of the drug. Discounting was not relevant, as the costs were incurred during a short time, and was therefore not performed. The price year was reported, which will aid the generalisability to other settings.
Other issues The authors reported that health economic studies based on the PROWESS trial results and some country-specific data had shown promising results for drotrecogin alfa (activated). The authors partially addressed the issue of generalisability to other settings when they assessed the impact of the three methodological approaches on their results. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis. The authors reported a number of further limitations. For example, the sub-group analysis was possibly biased because of the use of a limited country-specific patient sample in the costing study.
Implications of the study The authors recommended that the present study should be completed and updated when more information becomes available from local treatment practice of the drug and from ongoing trials.
Bibliographic details Hjelmgren J, Persson U, Tennvall G R. Local treatment pattern versus trial-based data: a cost-effectiveness analysis of drotrecogin alfa (activated) in the treatment of severe sepsis in Sweden. American Journal of Therapeutics 2005; 12(5): 425-430 Other publications of related interest Lucioni C, Guidi L, Mazzi S, et al. The treatment of sepsis patients with drotrecogin alfa (activated); an economic evaluation with reference to Italy. Value Health 2002;5:562.
Davies A, Hutton J, Ridley S, et al. The PROWESS economic team. Cost-effectiveness of drotrecogin alfa (activated) in treating severe sepsis in the UK. Intensive Care Med 2002;28 Suppl 1:S161.
Angus DC, Linde-Zwirble WT, Clermont G, et al. Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis. Crit Care Med 2003;31:1-11.
Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents /economics /therapeutic use; Cost-Benefit Analysis; Delivery of Health Care /economics /utilization; Drug Costs; Drug Utilization; Female; Humans; Male; Middle Aged; Models, Economic; Practice Patterns, Physicians'; Protein C /economics /therapeutic use; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins /economics /therapeutic use; Sepsis /drug therapy /physiopathology; Sweden AccessionNumber 22005006630 Date bibliographic record published 30/09/2006 Date abstract record published 30/09/2006 |
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