|Strategies for the management of suspected heparin-induced thrombocytopenia: a cost-effectiveness analysis
|Patrick A R, Winkelmayer W C, Avorn J , Fischer M A
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.
This study assessed the cost-effectiveness of four strategies for the diagnosis and treatment of heparin-induced thrombocytopenia (HIT). Testing for HIT in critical care patients was found not likely to be cost-effective, except in high-prevalence settings, which did favour strategies including testing and a more rapid switch to a direct thrombin inhibitor. The prior probability of HIT determined the most appropriate strategy. The study methodology was appropriate and well described, enhancing the validity of the authors’ conclusions.
Type of economic evaluation
The objective was to assess the cost-effectiveness of four strategies for the diagnosis and subsequent treatment of heparin-induced thrombocytopenia (HIT) in patients on heparin therapy.
The four strategies were: no antibody testing, continue with heparin (No Test Wait); antibody testing, continue with heparin while awaiting the test results (Test Wait); antibody testing, switch to a direct thrombin inhibitor (DTI) while awaiting the test results (Test Switch); and no antibody testing, switch to a DTI (No Test Switch). The DTI was argatroban and the heparin-platelet factor four test was used for antibody testing.
USA/hospital critical care unit.
This economic evaluation was based on a decision tree, which simulated the four patient management strategies and projected the future costs and benefits. A lifetime horizon was considered and the authors stated that a societal perspective was adopted.
A systematic literature search identified the potential sources of clinical inputs for the model. Whenever possible, the authors used data from meta-analyses, comparative trials, and studies with large sample sizes. For example, randomised controlled trials were used to obtain the clinical effectiveness and safety of argatroban and the patients' characteristics. Meta-analyses were used to obtain the risk of adverse events while on heparin, while the accuracy of the antibody test was taken from a review. The methods used to pool the data from multiple sources or to calculate the mean estimates from those found in the literature were not described.
Monetary benefit and utility valuations:
The utility valuations were derived from a literature search of Medline and of the Cost-Effectiveness Analysis Registry. The methodology and instruments used in the sources of data were not reported, although the utility weights associated with each event were provided.
Measure of benefit:
Quality-adjusted life-years (QALYs) were used as the summary benefit measure and were combined with costs. They were discounted at an annual rate of 3%.
The analysis included the costs associated with drugs and treatment of adverse events (thrombosis, myocardial infarction, ischaemic stroke, major bleed, and amputation). These costs were presented as macro-categories. Drug consumption patterns were derived from published clinical trials and valued using average wholesale prices from the Red Book. The costs and resource use data for adverse events came from published studies identified via a Medline search. All costs were in US dollars ($) and the price year was 2004. Discounting was relevant given the long-term horizon of the analysis and an annual rate of 3% was applied to future costs.
Analysis of uncertainty:
A deterministic approach was used to deal with the issue of uncertainty. A univariate sensitivity analysis was carried out on individual model inputs, with the most influential inputs being further investigated in a two-way sensitivity analysis. The ranges of values investigated appear to have been derived from the published sources.
The lifetime cost per patient was $580 with No Test Wait, $1,669 with Test Wait, $2,118 with Test Switch, and $3,805 with No Test Switch.
The expected QALYs were 11.5553 with No Test Wait, 11.5619 with Test Wait, 11.5636 with Test Switch, and 11.5648 with No Test Switch.
The incremental analysis suggested that No Test Wait was the reference strategy and the incremental cost per QALY gained relative to the next most effective non-dominated strategy was $163,396 with Test Wait, $274,367 with Test Switch, and $1,411,323 with No Test Switch.
The sensitivity analysis identified the probability of HIT as the most critical variable. As the probability of HIT increased from the base-case of 3% to 75%, the attractiveness of the strategies in which patients were administered a DTI more quickly (Test Switch and No Test Switch) increased also. For example, for a 10% probability of HIT, the incremental cost per QALY gained with Test Wait fell to $39,363 and that of Test Switch fell to $65,492.
Another important finding was that the strategies in which patients were switched to a DTI more quickly became more attractive as the probability of having a thrombotic event while receiving heparin increased for HIT patients.
Reductions in drug prices did not substantially alter these findings.
The authors concluded that testing for HIT in critical care patients with thrombocytopenia was not likely to be cost-effective, except in high-prevalence settings, where strategies which included testing and a more rapid switch to a DTI appeared to be more cost-effective. The accurate selection of patients based on their prior probability of HIT determined the most appropriate strategy.
The four strategies appear to have been appropriately selected in order to cover all possible options for the management of patients at risk of HIT. Another DTI was available, but was not included as a alternative strategy because of a lack of head-to-head studies and methodological differences between the two DTIs.
The systematic and comprehensive approach used to identify the sources of the clinical data was appropriate. The authors stated that valid sources were used, whenever possible. This should ensure the appropriateness of the clinical inputs. Uncertain estimates were varied in the sensitivity analysis. QALYs are a valid benefit measure, given the impact of this disease on quality of life. They are also comparable with the benefits of other health care interventions. The values of utility estimates were reported together with the approach used to identify the relevant sources. However, the instruments used to elicit the preferences and, in general, the methodology used, were not described.
: A societal perspective was adopted, but indirect costs (productivity losses) were presumably not included because of the advanced age of the typical patient (64 years). With this presumption, the categories of costs appear to be consistent with the perspective. The costs of adverse events were not broken down into individual items. This is a quite common approach with long-term disease costs, but reduces the transparency and generalisability of the economic analysis. The details of the sources used to value the adverse events were not provided, but the authors stated that they included US sources, conducted within the last 10 years, with clear descriptions of their costing methodology.
Analysis and results:
An incremental approach was appropriately used to combine the costs and benefits, and the findings were clearly presented. The issue of uncertainty was selectively addressed by means of a deterministic sensitivity analysis which focused on individual model inputs. Clearly, the use of a more comprehensive approach would have been useful, but the findings were robust, except in a small number of scenarios. The authors acknowledged that HIT is a relatively rare condition, which reduces the availability of good-quality evidence. It was also noted that the transferability of these findings to other settings might have been limited by the use of US economic data.
The study methodology was appropriate and well described. The authors’ conclusions are likely to be valid.
Patrick A R, Winkelmayer W C, Avorn J , Fischer M A. Strategies for the management of suspected heparin-induced thrombocytopenia: a cost-effectiveness analysis. PharmacoEconomics 2007; 215(11): 949-961
Other publications of related interest
Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996;101:502-7.
Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330-5.
Lewis BE, Wallis DE, Leya F, et al. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 2003;163:1849-56.
Subject indexing assigned by NLM
Anticoagulants /adverse effects; Cost-Benefit Analysis; Critical Care; Decision Trees; Heparin /adverse effects; Heparin Antagonists /economics /therapeutic use; Humans; Models, Statistical; Quality-Adjusted Life Years; Thrombocytopenia /chemically induced /economics /therapy
Date bibliographic record published
Date abstract record published