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Cost-effectiveness of low-molecular weight heparin and unfractionated heparin in treatment of deep vein thrombosis |
Rodger M, Bredeson C, Wells P S, Beck J, Kearns B, Huebsch L B |
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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 Unfractionated heparin (UFH) and low-molecular weight heparins (LMWH) used for the treatment of above knee deep vein thrombosis in both inpatient and outpatient settings.
Type of intervention Treatment and secondary prevention.
Economic study type Cost-effectiveness analysis.
Study population Patients with acute deep vein thrombosis.
Setting Hospital. The economic analysis was conducted in Ottawa, Ontario, Canada.
Dates to which data relate Effectiveness data were taken from studies published between January 1984 and April 1996. Resource use data were taken from a review of hospital cases in a general hospital in 1995/1996. 1995 price years were used in the analysis.
Source of effectiveness data Effectiveness data were derived from a review (meta-analysis) of previously published studies
Modelling A decision analysis model was constructed using Decision Tree Software (Tree Age 3.0.2, 1988; Simware, Williamstown, Mass, USA), to combine information on probabilities of effectiveness derived from a meta-analysis, with information on resource use for patients with DVT derived from hospital records. The duration of events considered in the model was three months and specifically the following four arms were considered:
(1) inpatient UFH only,
(2) inpatient LMWH only,
(3) outpatient LMWH for suitable patients, with remaining patients receiving LMWH on an inpatient basis, and
(4) outpatient LMWH for suitable patients, with remaining patients receiving UFH on an inpatient basis.
Outcomes assessed in the review The primary outcomes assessed were the probabilities of major haemorrhage, recurrence of DVT within 3 months, and death within three months following treatment with either UFH or LMWH.
Study designs and other criteria for inclusion in the review Eligible studies had to compare intravenously monitored UFH with weight-adjusted subcutaneous unmonitored LMWH, study patients had to be evaluated for major haemorrhage whilst receiving heparin and for recurrence of DVT within three months, and mortality rates had to be measured for a three month period.
Sources searched to identify primary studies MEDLINE was searched for relevant studies published from January 1984 to April 1996.
Criteria used to ensure the validity of primary studies Outcomes in studies must have been determined using a blinded assessment method.
Methods used to judge relevance and validity, and for extracting data Articles were reviewed independently by two reviewers and disagreements resolved by consensus. Relative risk, risk reduction and significance tests were conducted using a random effects model.
Number of primary studies included Methods of combining primary studies Meta-analysis and pooled analysis.
Investigation of differences between primary studies Heterogeneity between studies was tested using the Q statistic for overall heterogeneity, with a p value of less than 0.05 required for statistically significant heterogeneity.
Results of the review The probabilities of a major haemorrhage whilst receiving LMWH and UFH respectively were estimated to be 1.2% and 2.3%, (mean difference -1.1%, CI: -2.4% to - 0.3%) The probability of major haemorrhage leading to death was estimated to be 13.0%. Similarly the probabilities of venous thromboembolism whilst receiving LMWH and UFH respectively were estimated to be 4.4% and 7.0% (mean difference -2.6%, CI: -4.5% to - 0.7%). The probability of venous thromboembolism leading to death was estimated to be 12.0%. The probabilities of death following LMWH and UFH treatment respectively were estimated to be 4.1% and 6.0%, (mean difference -1.9%, CI: -3.6% to - 0.4%)
Measure of benefits used in the economic analysis The benefit measure was lives saved.
Direct costs Costs of treatment and complications associated with UFH and LMWH treatment were estimated using data from a sample of 105 patients diagnosed with DVT at a general hospital. UFH treatment costs were identified directly from these records whilst costs for LMWH treatment included an estimate of savings in nursing time in comparison with UFH treatment (using a time and motion study), and all drug acquisition and preparation costs. For outpatient treatment estimates were made using actual costs of outpatient care in a medical day care unit, including costs of injections, nursing assessment and monitoring. Costs of treating major haemorrhages were also based on actual treatment costs at the study hospital. It was assumed that costs of treating recurrent events were the same as those of the initial events. Costs were estimated from the perspective of the hospital and 1995 prices were used. Discounting was not used in the analysis, this was appropriate given the short duration of the study.
Sensitivity analysis One way, best and worst case sensitivity analyses were performed. However, only the worst case sensitivity analysis, in which all cost, efficacy and safety data were varied to favour UFH, was discussed in the paper.
Estimated benefits used in the economic analysis Three month mortality rates for inpatients treated with UFH and LMWH were 7.0% and 4.7% respectively. Similarly, outpatient treatment with LMWH or inpatient treatment with UFH, were 6.0% compared with 4.7% if all patients (both inpatients and outpatients) were treated with LMWH.
Cost results The mean costs per patient for 3 months of care for inpatients treated with UFH and LMWH were Can$3,313 and Can$3,150 respectively. Similarly, mean costs per patient for outpatient treatment with LMWH or inpatient treatment with UFH were Can$2,634 compared with Can$2,546, if all patients, both inpatients and outpatients, were treated with LMWH. Costs of adverse events such as major haemorrhages and recurrence of venous thrombosis were included in these estimates.
Synthesis of costs and benefits A synthesis was not undertaken by the authors since the intervention was the dominant strategy. However, in the worse case sensitivity analysis the cost per life saved would be Can$25,667.
Authors' conclusions LMWH is more cost effective then UFH for patients requiring treatment for acute DVT in both inpatient and outpatient settings. These conclusions were robust in sensitivity analysis.
CRD COMMENTARY - Selection of comparators A justification was provided for the comparator used. UFH is a traditional treatment for acute deep venous thrombosis.
Validity of estimate of measure of benefit An estimates of benefits was based on a meta-analysis of previously published trials. Sufficient information was provided on the criteria used for searching for and identifying studies. However, it would be have been useful to know whether non-English language papers were considered in the literature review. The paper also appears not to state the number of primary studies actually identified.
Validity of estimate of costs Sufficient data were provided on cost estimates. Only direct costs were considered and, as the authors acknowledge, future studies may wish to consider also the costs to others such as society. An estimate of these costs may be likely to increase the advantage of LMWH over UFH treatment.
Other issues Cost and resource estimates used in the analysis may not be generalisable to settings outside Ontario.
Source of funding Dr M A Rodger is the recipient of a Thrombosis interest Group Research Fellowship. Dr P s Wells is the recipient of a Research Scholarship from the Heart and Stroke Foundation of Canada.
Bibliographic details Rodger M, Bredeson C, Wells P S, Beck J, Kearns B, Huebsch L B. Cost-effectiveness of low-molecular weight heparin and unfractionated heparin in treatment of deep vein thrombosis. CMAJ: Canadian Medical Association Journal 1998; 159: 931-938 Other publications of related interest Commentary in: ACP Journal Club 1999;130(2):53.
Indexing Status Subject indexing assigned by NLM MeSH Canada; Cost-Benefit Analysis; Decision Trees; Drug Costs; Heparin /economics /therapeutic use; Heparin, Low-Molecular-Weight /economics /therapeutic use; Humans; Treatment Outcome; Venous Thrombosis /drug therapy /economics AccessionNumber 21998008252 Date bibliographic record published 30/04/2000 Date abstract record published 30/04/2000 |
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