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Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis |
Caro J J, Getsios D, Caro I, O'Brien J A |
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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 use of unfractionated heparin (UFH) versus low molecular weight heparin (i.e. tinzaparin sodium, TS) for the treatment of patients presenting with deep venous thrombosis (DVT), with or without pulmonary embolism (PE). The patients received either 175 International Factor Xa inhibitory units/kg of TS administered subcutaneously once daily, or standard UFH for an average of 6 days, as suggested in published trials.
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population The study population comprised a hypothetical cohort of patients presenting with DVT, with or without PE.
Setting The setting was primary and secondary care. The economic study was conducted in the USA.
Dates to which data relate The effectiveness and resource use data were obtained mainly from studies published between 1992 and 1997. The price year was 1999.
Source of effectiveness data The effectiveness evidence was derived from a review of completed studies and authors' assumptions.
Modelling An analytic modelling approach was used to assess the long-term costs and benefits of the two treatments under evaluation. A short-term model, based on trial data, spanned the 3 months following the initial acute DVT episode. The long-term model considered long-term data and used regression techniques to extrapolate the short-term outcomes for up to 50 years.
Outcomes assessed in the review The outcomes estimated in the review were:
the event and complication rates associated with the two treatments;
life table data for individuals with DVT;
the long-term hazards of recurrent thromboembolic events and post-phlebitic syndrome; and
the health utilities associated with specific health states (using the time trade-off method).
Study designs and other criteria for inclusion in the review A formal review of the literature was not conducted. Of the primary studies, the authors stated only that one was a randomised clinical trial (involving 435 patients) and another was a longitudinal study. Utility was derived from a study involving 1,356 adult Americans. Details of the other sources were not provided.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Five primary studies were considered.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The event and complication rates were as follows:
the rates of major bleeds were 5% with UFH and 2.8% with TS;
the rates of minor bleeds were 6.4% (UFH) and 6% (TS), respectively;
the rates of recurrent DVT were 4.1% (UFH) and 1.4% (TS);
the rates of fatal PE were 1.8% (UFH) and 0.5% (TS);
the rates of nonfatal PE were 1.4 in both groups;
the rates of thrombocytopenia were 0.5% (UFH) and 1.4% (TS);
the rates of DVT-related deaths were 4.1% (UFH) and 0.9% (TS);
the rates of DVT-unrelated deaths were 3.4% in both groups;
the rates of mild post-phlebitic syndrome were 14.6% (UFH) and 13.4% (TS); and
the rates of severe post-phlebitic syndrome were 5.5% (UFH) and 3.2% (TS).
It was estimated that 19.2% of recurrent thromboembolic events would be PE and the remainder would be DVTs. In addition, 44.9% of recurrent thromboembolic events would be ipsilateral DVTs in patients who had not yet had an ipsilateral DVT.
The health utilities were not reported, but slight adjustments were made for patients with mild or severe post-phlebitic syndrome.
Methods used to derive estimates of effectiveness The authors made some assumptions that were used in the model.
Estimates of effectiveness and key assumptions It was assumed that the event rates estimated from the literature would be the same regardless of where TS was administered. Other assumptions were also made, but these were not reported clearly.
Measure of benefits used in the economic analysis The summary benefit measures used were survival and the quality-adjusted life-years (QALYs). These were calculated over the long term. Both were discounted at an annual rate of 3%.
Direct costs An annual discount rate of 3% was used since the costs were incurred over a long time. In general, the unit costs and the quantities of resources used were reported separately for most cost items. The health services included in the economic evaluation were drugs, initial hospitalisation for DVT, outpatient treatment, post-discharge care and the treatment of complications. Initial hospitalisation for DVT covered diagnostic workup in the emergency room, accommodation, ancillary and physician costs. Outpatient treatment covered the visit to the emergency room, drug administration, physician services and home visits by registered nurses. Post-discharge care included skilled nursing facilities, rehabilitation and home health care.
The cost/resource boundary of the study was that of the third-party payer. Resource use was derived from trial data and authors' assumptions (e.g. all patients would receive full inpatient treatment). Some costs were estimated from six all-payer, state 1996/1997 discharge databases, while other costs came from the literature or agency data. However, the sources of some items were not reported. Different scenarios for early discharge were considered. A cost-to-charge ratio of 0.61 was used to adjust data reported as charges. The costs were presented in 1999 values using the medical care component of the US Consumer Price Index.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were not considered.
Sensitivity analysis One-way, multi-way, and threshold sensitivity analyses were conducted to address the issue of variability in the data. The cost of TS, all non-heparin costs, complication rates with TS, and the discount rate were varied. The ranges used were reported only for some model inputs. The impact of alternative scenarios based on authors' assumptions was also considered.
Estimated benefits used in the economic analysis The mean survival per patient was 18.4 years with UFH and 18.94 years with TS. The difference was 0.90 years (discounted difference 0.60).
The mean QALYs per patient was 15.26 with UFH and 16.05 with TS. The difference was 0.79 (discounted difference 0.53).
Cost results The short-term costs per patient were $7,818 with UFH and $7,076 with TS. The difference was -$742.
The long-term costs per patient were $2,388 with UFH and $2,508 with TS. The difference was $121.
The total costs per patient were $10,205 with UFH and $9,584 with TS. The difference was -$621.
Synthesis of costs and benefits No incremental cost-effectiveness ratio was calculated because TS was the dominant strategy (both more effective and less costly). The results of the sensitivity analysis corroborated the dominance of TS, while changes in the model inputs further favoured the TS strategy. The costs of DVT treatment and complications had the greatest impact on the results, but the use of TS always led to cost-savings under reasonable scenarios. The threshold analysis showed that, even if TS was not better than UFH, there would be cost-savings as long as at least 3.8% of patients were treated as outpatients, or 5.8% were discharged after only 3 hospital days.
Authors' conclusions Tinzaparin sodium (TS) was the dominant strategy in comparison with unfractionated heparin (UFH) for the treatment of deep vein thrombosis (DVT) in the USA.
CRD COMMENTARY - Selection of comparators The authors stated that UFH was chosen as the basic comparator because it represented the standard treatment for patients with DVT. TS was a new drug that had recently been approved by the Food and Drug Administration for the treatment of DVT in the USA. Therefore, the choice of the comparators appears to have been appropriate. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The analysis of effectiveness used data derived from published studies, which appear to have been identified selectively. In fact, a review of the literature does not appear to have been undertaken to identify the relevant evidence. Limited information on the sources used was provided, which means that it is not possible to assess the validity of the primary estimates. However, the authors conducted extensive sensitivity analyses to address the issue of uncertainty in the model inputs. This enhanced the robustness of the results.
Validity of estimate of measure of benefit Both benefit measures used in the analysis were appropriate and could be compared with the benefits of other health care interventions. Appropriate discounting was applied. The source of the utility data was reported and it reflected the values of patients suffering from DVT.
Validity of estimate of costs The authors explicitly stated the perspective adopted in the study. As such, it appears that all the relevant categories of costs have been included in the analysis. The unit costs and most resource use data were reported, which enhances the possibility of replicating the study. The source of the costs was not reported for all items. The price year was given, which would facilitate reflation exercises in other settings. The costs were treated deterministically in the base-case, but all economic inputs were varied in the sensitivity analysis. This enhances the generalisability of the study to settings with different cost data.
Other issues The authors made extensive comparisons of their findings with those from other studies. They discussed the reasons for the different results obtained from the literature. However, the issue of the generalisability of the study results to other settings was not explicitly addressed, although the use of a sensitivity analysis had a positive impact on the external validity of the analysis. The study referred to patients with DVT and this was reflected in the conclusions of the analysis. The authors noted some limitations. For example, the use of efficacy data derived from a single trial, the use of non-US data for some outcomes, and the exclusion of the indirect costs. The authors stressed that the inclusion of the indirect costs would have further favoured the cost-effectiveness of TS.
Implications of the study The authors suggested that future studies should assess the cost-effectiveness of TS in specific sub-groups of patients, such as those with PE or cancer, who are obese or pregnant, or those who have had surgery.
Source of funding Supported in part by an unrestricted grant from DuPont Pharmaceuticals, Wilmington (DE), USA.
Bibliographic details Caro J J, Getsios D, Caro I, O'Brien J A. Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis. PharmacoEconomics 2002; 20(9): 593-602 Other publications of related interest Estrada CA, Mansfield CJ, Heudebert GR. Cost-effectiveness of low-molecular-weight heparin in the treatment of proximal deep vein thrombosis. Journal of General Internal Medicine 2000;15:108-15.
Gould MK, Dembitzer AD, Sanders GD, et al. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis: a cost-effectiveness analysis. Annals of Internal Medicine 1999;130:789-99.
Indexing Status Subject indexing assigned by NLM MeSH Ambulatory Care /economics; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Costs; Fibrinolytic Agents /economics /therapeutic use; Health Care Costs; Health Services Research; Heparin /economics /therapeutic use; Heparin, Low-Molecular-Weight /economics /therapeutic use; Hospitalization /economics; Humans; Longitudinal Studies; Models, Econometric; Quality-Adjusted Life Years; Treatment Outcome; United States; Value of Life /economics; Venous Thrombosis /drug therapy /economics AccessionNumber 22002008239 Date bibliographic record published 31/12/2004 Date abstract record published 31/12/2004 |
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