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DOI: 10.1148/radiol.2273020441
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(Radiology 2003;227:647-656.)
© RSNA, 2003

Evidence-based Practice

Cost-effectiveness Targets for Multi–Detector Row CT Angiography in the Work-up of Patients with Intermittent Claudication1

Karen Visser, PhD, Marc C. J. M. Kock, MD, Karen M. Kuntz, ScD, Magruder C. Donaldson, MD, G. Scott Gazelle, MD, PhD and M. G. Myriam Hunink, MD, PhD

1 From the Program for the Assessment of Radiological Technology (ART Program), Dept of Epidemiology and Biostatistics, and Dept of Radiology, Erasmus MC, University Med Center Rotterdam, Dr Molewaterplein 50, Rm Ee21-40B, 3015GE Rotterdam, the Netherlands (K.V., M.C.J.M.K., M.G.M.H.); Dept of Health Policy and Management, Harvard School of Public Health, Boston, Mass (K.M.K., G.S.G., M.G.M.H.); Division of Vascular Surgery, Brigham and Women’s Hosp, Boston, Mass (M.C.D.); and Decision Analysis and Technology Assessment Group, Dept of Radiology, Massachusetts General Hosp, Harvard Med School, Boston, Mass (G.S.G.). From the 2001 RSNA scientific assembly. Received Apr 15, 2002; revision requested Jun 19; revision received Jul 26; accepted Sep 23. Supported in part by the Netherlands Organization for Scientific Research. Address correspondence to K.V. (e-mail: k.visser@erasmusmc.nl).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To determine the costs, sensitivity for detection of significant stenoses, and proportion of equivocal multi–detector row computed tomographic (CT) angiography results in the work-up of patients with intermittent claudication that would make this imaging examination cost-effective compared with gadolinium-enhanced magnetic resonance (MR) angiography.

MATERIALS AND METHODS: A decision model was used to compare the societal cost-effectiveness of a new imaging modality with that of gadolinium-enhanced MR angiography. Main outcome measures were quality-adjusted life years (QALYs) and lifetime costs. By using threshold analysis of a given willingness to pay per QALY, target values for costs, sensitivity for detection of significant stenoses, and proportion of cases requiring additional work-up with intraarterial digital subtraction angiography owing to equivocal results of the new modality were determined. The base case evaluated was that of 60-year-old men with severe intermittent claudication and assumed an incremental cost-effectiveness threshold of $100,000 per QALY.

RESULTS: If treatment were limited to angioplasty, a new imaging modality would be cost-effective if the costs were $300 and the sensitivity was 85%, even if up to 35% of patients needed additional work-up. When both angioplasty and bypass surgery were considered as treatment options, a new imaging modality was cost-effective if the costs were $300, the sensitivity was higher than 94%, and 20% of patients required additional work-up.

CONCLUSION: Multi–detector row CT angiography, as compared with currently used imaging modalities such as MR angiography, has the potential to be cost-effective in the evaluation of patients with intermittent claudication.

© RSNA, 2003

Index terms: Arteries, stenosis or obstruction, 92.721 • Computed tomography (CT), angiography, 92.12916 • Cost-effectiveness • Radiology and radiologists, socioeconomic issues


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
The development of new diagnostic imaging modalities for the evaluation of peripheral arterial disease (PAD) is ongoing. Intraarterial digital subtraction angiography (DSA) has been used as the sole preinterventional imaging modality for the detection of PAD. DSA is still considered the reference standard and is associated with a small degree of risk of mortality (1,2). In the 1980s, duplex ultrasonography (US) was introduced into clinical practice (3,4). The addition of color guidance improved the diagnostic accuracy of this noninvasive modality (5), and US became a useful diagnostic tool that has the potential to replace a number of the DSA examinations performed (6). In the early 1990s, magnetic resonance (MR) angiography was developed for the work-up of PAD (7–9). MR angiography is minimally invasive and with gadolinium enhancement is highly accurate (10–12). Gadolinium-enhanced MR angiography can be used as the sole imaging examination in the planning of treatment for PAD (13–15).

Multi–detector row computed tomographic (CT) angiography has recently been developed as a potential imaging modality for the diagnosis of PAD. The preliminary results of studies to evaluate CT angiography are promising (16,17). Also, other examinations such as MR angiography with blood pool agents (18), MR angiography (19) or DSA with carbon dioxide as the contrast material (20), and duplex US with contrast material (21) have been suggested as new imaging modalities for the detection of PAD.

Currently, the future role of these imaging modalities is speculative. To determine whether a new imaging modality has the potential to be cost-effective, as compared with the modalities currently used in practice, the diagnostic accuracy, costs, and complications associated with the new modality should be known. In the early development of new technologies, these parameters are generally unknown and it is difficult to predict what the exact values for these parameters will be. However, because these values are known for the currently used modalities, it is possible to calculate the target values that a new modality should meet to be cost-effective compared with the modalities currently used for diagnostic work-up (22–24). Calculations of this kind can help focus not only the development of new modalities for the diagnostic work-up of PAD but also the development of new technologies in health care in general.

The purpose of our study was to determine the target values for diagnostic accuracy that would make multi–detector row CT angiography, as compared with gadolinium-enhanced MR angiography, cost-effective in terms of the following parameters: the sensitivity for detection of significant stenoses, the proportion of cases requiring additional work-up with DSA because of equivocal results, and the costs of multi–detector row CT angiography in the work-up of patients with intermittent claudication.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Decision Model
For the current study, we used a decision-analytic model that was developed to evaluate the societal cost-effectiveness of diagnostic imaging strategies for the work-up of patients with intermittent claudication (25). In this model, patients presented to the vascular surgery department with severe unilateral intermittent claudication (ie, ability to walk a maximum distance of <250 m), and on the basis of their medical history, physical examination results, and ankle-brachial index were referred for diagnostic imaging work-up. The probability of having at least one significant stenosis (ie, luminal diameter reduction > 50%) for patients with an ankle-brachial index of less than 0.90 is higher than 0.99 (26); therefore, we assumed that all patients had at least one significant stenosis in the suprainguinal or infrainguinal arterial tract. Patients with isolated infrapopliteal disease were not considered.

Diagnostic work-up with gadolinium-enhanced MR angiography consisted of localizing the lesion (ie, suprainguinal or infrainguinal) and determining the treatment plan (percutaneous angioplasty, bypass surgery, or supervised exercise program). Results were defined as equivocal when the examination was technically inadequate (eg, because of poor vessel opacification, incorrect timing, artifacts, or early venous filling) or for some other reason the examination did not enable formulation of a treatment plan (eg, discrepancy between symptoms and MR angiographic findings or doubt about the hemodynamic significance of a stenosis). Intraarterial DSA was performed when the MR angiography result was equivocal or could not be performed because of a contraindication (eg, claustrophobia). DSA was also performed when no significant lesion was localized at MR angiography; this outcome was considered to be a false result. Furthermore, we recognized that MR angiography could yield incorrect information, and, as a result, patients could be treated incorrectly.

For percutaneous treatment, we assumed that the DSA examination performed just prior to the procedure would correctly depict the findings that had been incorrectly depicted at MR angiography. If the percutaneous intervention procedure was then canceled, the costs were considered to be equal to the costs of performing DSA plus some extra expenses for the inefficient use of personnel, housing, and equipment. The rates of complication associated with planned but not performed angioplasty were considered to be equal to the rates of complication associated with diagnostic DSA. For bypass surgery, we assumed that an incorrect MR angiography result would not be detected unless the wrong arterial segment was bypassed, in which case the patient would still have symptoms and thus return to the hospital for DSA followed by repeat intervention. Figure 1 is a flowchart of the decision tree.



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  		Figure 1. Flow chart of decision tree. Equivocal test result (*) was defined as a technically inadequate imaging examination or an imaging result that did not enable a treatment plan to be formulated because of the depiction of calcified arterial walls. Two treatment scenarios ({dagger}) were considered: In the first scenario, that of minimally invasive treatment, patients underwent angioplasty if it was feasible; otherwise, they were started on a supervised exercise program. In the second scenario, that of more invasive treatment, patients underwent angioplasty if it was feasible; otherwise they underwent bypass surgery.

 
In clinical practice, bypass surgery is sometimes considered too invasive for the treatment of intermittent claudication and patients in whom angioplasty is not feasible are treated conservatively. To reflect clinical practice, we evaluated two scenarios of treatment after initial imaging work-up. In the first scenario, that of minimally invasive treatment, percutaneous treatment was performed in those patients in whom a lesion suitable for percutaneous treatment had been detected at imaging work-up; otherwise, the patients were started on a supervised exercise program. The feasibility of percutaneous treatment for lesions in the aortoiliac or femoropopliteal segment was consistent with published guidelines (27). During follow-up, the patients could have developed recurrent symptoms of intermittent claudication or critical limb ischemia, in which case a second percutaneous treatment was performed if feasible. Bypass surgery was performed in only those patients with critical limb ischemia in whom angioplasty was not feasible.

In the second scenario, that of more invasive treatment, bypass surgery was performed in those patients who did not have lesions that were suitable for angioplasty. For recurrent symptoms of intermittent claudication or critical limb ischemia, a second treatment was considered: percutaneous treatment, if feasible; otherwise bypass surgery was performed. For those patients with a history of coronary artery disease, it was assumed, because of the higher complication rates for these individuals, that bypass surgery could be performed only if the patient developed critical limb ischemia. Finally, there are always some patients (5%, assumption) who have imaging results indicating that no revascularization would be considered unless the patient developed critical limb ischemia.

Data Sources
Diagnostic examination characteristics.—Values for the sensitivity of gadolinium-enhanced MR angiography in the detection of significant stenoses were available from a previously performed meta-analysis (12). The probabilities of treatment recommendations based on gadolinium-enhanced MR angiography findings were derived from the literature (15). The examination characteristics of gadolinium-enhanced MR angiography were available from studies in which MR angiography was compared with DSA, which was considered the reference standard (12,15,28). We incorporated the risks of morbidity and mortality associated with DSA (1,2) and assumed that gadolinium-enhanced MR angiography did not involve risks. The diagnostic DSA examinations were planned in such a way that angioplasty could be performed immediately afterward if the patient had a suitable lesion. The examination characteristics of MR angiography and DSA are presented in Table 1.


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  		TABLE 1. Test Characteristics for Gadolinium-enhanced MR Angiography and Intraarterial DSA

 
Treatment and follow-up.—Data on treatment and follow-up were derived from a Monte Carlo Markov model in which 100,000 patients for each possible diagnostic outcome were simulated (29). In this decision-analytic model the cost-effectiveness of supervised exercise versus that of invasive treatment options such as angioplasty and bypass surgery was evaluated. The Markov model allowed for treatment of recurrent symptoms and for treatment of symptoms involving the contralateral limb. The lesions were predominantly suprainguinal or infrainguinal (56% vs 44%, respectively); 51% of the suprainguinal lesions versus 18% of the infrainguinal lesions were suitable for percutaneous treatment. These data were available from a series of 722 patients from the Brigham and Women’s Hospital in Boston (29).

Invasive treatment for suprainguinal lesions consisted of angioplasty with selective stent placement and aortic bifurcation surgery. Invasive treatment for infrainguinal lesions consisted of angioplasty and either femoropopliteal or femoroinfrapopliteal bypass surgery. Patency rates were available from published meta-analyses (30–32). The annual rate of critical limb ischemia in patients with intermittent claudication was 0.017 for patients younger than 65 years (33) and 0.036 for patients aged 65 years and older (33–36). Limb amputation was performed if treatment for critical limb ischemia failed and three invasive interventions had already been performed in the diseased limb.

Costs.—Medicare reimbursement rates were used for the costs of gadolinium-enhanced MR angiography and DSA and yielded estimates of $574 and $1,183, respectively (Table 2). Costs for revascularization vary more widely among patients than do costs for diagnostic work-up; therefore, we decided to use the costs available from a study that was performed to assess the costs of revascularization procedures for PAD as a function of patient characteristics (37). These costs were adjusted for the age, sex, history of coronary artery disease, and presenting symptoms (intermittent claudication vs critical limb ischemia) of patients. The estimated costs were $25,790 for aortic bifurcation surgery, $8,290 for suprainguinal angioplasty, $18,110 for infrainguinal bypass surgery, and $4,480 for infrainguinal angioplasty (Table 2). Although the costs of amputations vary widely among patients, we used Medicare reimbursement rates because amputations are rare among patients with intermittent claudication—and, thus, cost estimates have little effect on the results—and a more elaborate cost-accounting analysis was not within the scope of this study.


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  		TABLE 2. Costs and Health-related Quality of Life

 
The costs of below-the-knee amputation, including transmetatarsal amputations, and above-the-knee amputation were $8,550 and $15,830, respectively (Table 2). The estimated cost of a supervised exercise program was $4,417 per year and comprised mainly the expenses for the patient time spent walking, and follow-up visits in the hospital were included (29). The extra costs incurred for 1 hour of inefficient use of personnel, housing, and equipment in the case of a planned but not performed angioplasty were estimated to be $316 (38), which was added to the costs of a diagnostic DSA examination. All costs were converted to 1998 U.S. dollars by using the consumer price index (United States Bureau of Labor Statistics data) (41).

Health-related quality of life.—Estimated health values for patients with intermittent claudication were available from a study performed with participants in an exercise program in the Netherlands (39). These values were derived from responses to the EuroQol-5D (a generic questionnaire on quality of life), which were converted to time trade-off values. The values were 0.79 for patients with no or mild claudication and 0.71 for those with severe claudication (Table 2). The estimated health values for patients with critical limb ischemia, amputation below the knee (including transmetatarsal amputations), and amputation above the knee were available from a study conducted among the general public (40). Scenarios describing these three health states were presented, and time trade-off estimates were calculated. For patients with critical limb ischemia, the utility estimate was 0.35 (40) (Table 2). The estimated health value for patients who had undergone below-the-knee amputation was 0.61, whereas that for patients who had undergone above-the-knee amputation was 0.20 (40) (Table 2).

Determination of Thresholds
Cost-effectiveness analysis was performed to determine whether multi–detector row CT angiography, as compared with gadolinium-enhanced MR angiography, would be cost-effective in the work-up of patients with intermittent claudication. Lifetime costs and quality-adjusted life years (QALYs) were calculated (with a discount rate of 3%) (42), and a strategy was considered to be cost-effective if the additional cost per QALY did not exceed the society’s willingness to pay—that is, the amount of money that society is willing to pay for one additional QALY. For these analyses, we varied the cost-effectiveness threshold between $50,000 and $250,000 per QALY gained and used a threshold of $100,000 per QALY gained for the baseline analysis.

On the basis of the analysis, we determined what combinations of costs, sensitivity for detection of significant stenosis, and proportion of patients requiring additional work-up with DSA owing to equivocal CT angiography results (eg, because of technically failed examinations, artifacts, or vessel wall calcifications) would be required for multi–detector row CT angiography to be cost-effective compared with MR angiography. To determine these thresholds for a new imaging modality, we had to make assumptions about the risks involved and about the treatment recommendations based on multi–detector row CT angiography findings. In terms of the mortality- and morbidity-related risks associated with CT angiography, we assumed that these risks equaled those that are associated with the use of a low-osmolality contrast agent: probabilities of 9.0 x 10-6 for mortality risk and 3.1 x 10-4 for morbidity risk (43). Furthermore, the probabilities of a given treatment being recommended on the basis of CT angiography findings were assumed to be the same as those for MR angiography (Table 1). For sensitivity analysis, we assumed that the probabilities of a given treatment being recommended on the basis of CT angiography findings were the same as those recommended on the basis of duplex US (44) or DSA findings.

In a base-case analysis, cohorts of 60-year-old men with symptoms of severe unilateral claudication for 1 year, an ankle-brachial index of 0.70, and no history of coronary artery disease were evaluated. Target values for CT angiography in both the minimally invasive scenario and the more invasive treatment scenario were determined. Two other patient cohorts were considered: 40-year-old men with characteristics similar to those in the base case and 70-year-old men with a history of coronary artery disease and other characteristics similar to those in the base case. Women were not considered in this analysis because the results of previous analyses showed that the results of treatment for women were similar to the results of treatment for men (29). In the sensitivity analysis, the target criteria for CT angiography that would make this examination, as compared with DSA, cost-effective were determined. Also, sensitivity analyses were performed to determine the estimated health value with no or mild claudication (range, 0.75–0.83) and the costs of revascularization (50% and 150% of baseline estimates), because previous analyses have shown that the results of evaluating treatment for patients with intermittent claudication were sensitive for these parameters (29).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Minimally Invasive Treatment Scenario
In the minimally invasive treatment scenario, MR angiography yielded 6.1487 QALYs at a cost of $21,942. With use of a societal willingness to pay of $100,000 per QALY, a new imaging modality was equivalent to MR angiography in terms of cost-effectiveness if the cost of the modality was $420, the sensitivity for detection of significant stenosis was 90%, and 20% of the patients required additional work-up owing to equivocal CT angiography results. With these conditions and with the assumption of a threshold incremental cost-effectiveness ratio of $100,000 per QALY, the strategy with the new imaging modality yielded 6.1490 QALYs at a cost of $21,965. The distribution of events and treatment after the initial examination are presented in Table 3.


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  		TABLE 3. Distribution of Events after Initial Diagnostic Work-up for Base-Case Analysis

 
Target values for the costs and sensitivity of a new modality that would make it cost-effective compared with MR angiography are shown in Figure 2. For example, if CT angiography cost $300 or less and had a sensitivity of at least 85%, it would be cost-effective compared with MR angiography, even if up to 35% of patients needed additional work-up after undergoing the new modality. If the proportion of patients who required additional work-up with DSA decreased, a higher cost for CT angiography would be acceptable.



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  		Figure 2. Graph illustrates results of base-case analysis: a 60-year-old man. Target values of the costs and sensitivity for detection of significant stenosis of a new imaging modality in the minimally invasive treatment scenario and with a threshold for society’s willingness to pay of $100,000 per QALY gained are plotted. The lines of plotted values represent combinations of costs and sensitivity that would make a new modality cost-effective compared with gadolinium (Gd)-enhanced MR angiography, based on the proportion of patients who would require additional work-up. * = 35% of patients requiring additional work-up, {blacksquare} = 20% of patients requiring additional work-up, {circ} = 5% of patients requiring additional work-up. CT angiography would be cost-effective compared with MR angiography if the combination of costs and sensitivity for a new modality was to the left of the line. If, however, the combination of costs and sensitivity for CT angiography was to the right of the line, then MR angiography would be more cost-effective.

 
More Invasive Treatment Scenario
In the more invasive treatment scenario, the MR angiography strategy yielded 6.2137 QALYs at a cost of $48,965. With the assumption of a threshold incremental cost-effectiveness ratio of $100,000 per QALY, the new imaging modality would be equivalent to MR angiography in terms of cost-effectiveness if the costs were $673, the sensitivity for detection of significant stenosis was 95%, and 20% of the patients required an additional DSA examination owing to equivocal CT angiography results. With these conditions, the strategy involving a new imaging modality would yield 6.2151 QALYs at a cost of $49,102. Target values for the costs and sensitivity of a new imaging modality are presented in Figure 3. If, for example, CT angiography cost only $300 and 20% of patients required an additional DSA examination, then CT angiography would still need to have a sensitivity of 94% or higher to be cost-effective compared with MR angiography. The distribution of events and treatment after the initial examination in the more invasive treatment scenario also are presented in Table 3.



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  		Figure 3. Graph illustrates results of base-case analysis: a 60-year-old man. Target values of the costs and sensitivity for detection of significant stenosis of a new imaging modality in the more invasive treatment scenario and with a threshold for society’s willingness to pay of $100,000 per QALY gained are plotted. The lines of plotted values represent combinations of costs and sensitivity that would make a new modality cost-effective compared with gadolinium (Gd)-enhanced MR angiography, based on the proportion of patients who would require additional work-up. * = 35% of patients requiring additional work-up, {blacksquare} = 20% of patients requiring additional work-up, {circ} = 5% of patients requiring additional work-up. CT angiography would be cost-effective compared with MR angiography if the combination of costs and sensitivity of CT angiography was above the line. If, however, the combination of costs and sensitivity of CT angiography was below the line, then the new modality would not be cost-effective.

 
Sensitivity Analysis
The target values for a new imaging modality did not change substantially when society’s willingness to pay was varied (Table 4). For 40-year-old men, the target criterion for the cost of a new imaging modality was more lenient (Figs 4, 5), whereas for 70-year-old men with a history of coronary artery disease, the target criterion was stricter—that is, only the minimally invasive treatment scenario was considered (Fig 6). If it was assumed that the capabilities of a new imaging modality in facilitating the selection of a treatment plan were the same as those of duplex US, then either the target values for the new imaging modality would be stricter—that is, the minimally invasive treatment scenario would be considered—or the new imaging modality would not be cost-effective compared with MR angiography—that is, the more invasive treatment scenario would be considered. Assuming that a new imaging modality would have the same capabilities as DSA in facilitating the selection of a treatment made the target criteria more lenient (Table 4).


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  		TABLE 4. Combinations of Target Values for a New Imaging Examination to Be Cost-Effective, as Compared with Gadolinium-enhanced MR Angiography, for a Threshold of a Society’s Willingness to Pay of $100,000 per QALY Gained

 


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  		Figure 4. Alternative case: a 40-year-old man. Target values of the costs and sensitivity for detection of significant stenosis of a new imaging modality in the minimally invasive treatment scenario and with a threshold for society’s willingness to pay of $100,000 per QALY gained are plotted. The lines of plotted values represent combinations of costs and sensitivity that would make a new modality cost-effective compared with gadolinium (Gd)-enhanced MR angiography, based on the proportion of patients who would require additional work-up. * = 35% of patients requiring additional work-up, {blacksquare} = 20% of patients requiring additional work-up, {circ} = 5% of patients requiring additional work-up. CT angiography would be cost-effective compared with MR angiography if the combination of costs and sensitivity of the new modality was to the left of the line. If, however, the combination of costs and sensitivity of CT angiography was to the right of the line, then MR angiography would be more cost-effective.

 


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  		Figure 5. Alternative case: a 40-year-old man. Target values of the costs and sensitivity for detection of significant stenosis of a new imaging modality in the more invasive treatment scenario and with a threshold for society’s willingness to pay of $100,000 per QALY gained are plotted. The lines of plotted values represent combinations of costs and sensitivity that would make a new modality cost-effective compared with gadolinium (Gd)-enhanced MR angiography, based on the proportion of patients who would require additional work-up. * = 35% of patients requiring additional work-up, {blacksquare} = 20% of patients requiring additional work-up, {circ} = 5% of patients requiring additional work-up. CT angiography would be cost-effective compared with MR angiography if the combination of costs and sensitivity of CT angiography was above the line. If, however, the combination of costs and sensitivity of CT angiography was below the line, then the new modality would not be cost-effective.

 


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  		Figure 6. Alternative case: a 70-year-old man with a history of coronary artery disease. Target values of the costs and sensitivity for detection of significant stenosis of a new imaging modality in the minimally invasive treatment scenario and with a threshold for society’s willingness to pay of $100,000 per QALY gained are plotted. The lines of plotted values represent combinations of costs and sensitivity that would make a new modality cost-effective compared with gadolinium (Gd)-enhanced MR angiography, based on the proportion of patients who would require additional work-up. * = 35% of patients requiring additional work-up, {blacksquare} = 20% of patients requiring additional work-up, {circ} = 5% of patients requiring additional work-up. CT angiography would be cost-effective compared with MR angiography if the combination of costs and sensitivity of the new modality was to the left of the line. If, however, the combination of costs and sensitivity of CT angiography was to the right of the line, then the new imaging modality would not be cost-effective.

 
In the sensitivity analysis, we compared a new imaging modality with DSA (Table 4). In the minimally invasive treatment scenario, the target criterion for the cost of a new modality was more lenient. In the more invasive treatment scenario, a new modality would not be cost-effective compared with DSA with the assumptions that we made, even if the sensitivity was 100% and no patients required additional work-up with DSA. If, in addition, we assumed that a new imaging modality had the same capabilities as DSA in facilitating the recommendation of a treatment and involved no risks, the new modality, regardless of its costs, would be more cost-effective than DSA.

There was an inverse relationship between the health-related quality of life with no or mild intermittent claudication and the estimated costs of a new imaging modality. The costs for the new imaging modality would need to be lower if the quality of life was higher. If the costs for the revascularization were higher than our baseline estimate, the new modality would potentially have a higher cost. However, the differences in estimated target values for the range in health-related quality of life estimates and the range in cost of revascularization were modest (Table 4).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
In the current study, we determined target values for multi–detector row CT angiography in the pretreatment work-up of patients with intermittent claudication. When we compared CT angiography with gadolinium-enhanced MR angiography, the current imaging examination performed for work-up, the observed target values seemed possible to achieve. Compared with the target values for DSA, the target values for CT angiography would be attainable if angioplasty was considered as the only treatment option. With the assumptions that we made about CT angiography—namely, that it involves minimal risks and could lead to incorrect recommendations for treatment—DSA would always be more cost-effective than CT angiography if both angioplasty and bypass surgery were considered as treatment options. If, however, we assumed that CT angiography involved no risks and had diagnostic accuracy that was comparable to that of DSA, the reference standard, then CT angiography would be more cost-effective than DSA. In terms of developing new imaging modalities, it is important that the new modality has a fairly low cost and high sensitivity for the detection of significant stenoses.

Our study was limited by the fact that we used various data sources and made a number of assumptions to keep the model tractable. Such limitations are inherent to decision models and cost-effectiveness analyses. For instance, in our model we considered DSA the reference-standard examination; this precedent is well established in the literature on the diagnostic work-up of patients with PAD (12). Assuming that DSA is the reference standard implies that the new imaging modalities that are potentially more effective than DSA could not be evaluated with the model that we used.

Furthermore, with the described model it was assumed that MR angiography and CT angiography were clinically interchangeable; however, this assumption may not be realistic. Patients with renal insufficiency might be better served by undergoing MR angiography to avoid the nephrotoxicity of iodinated contrast agents, whereas patients with contraindications to MR angiography, such as those who have a pacemaker or are claustrophobic, might be better served by undergoing CT angiography. However, patients with renal insufficiency, pacemakers, or claustrophobia constitute the minority of PAD cases, whereas the described model addresses what the primary choice of imaging should be and allows for secondary imaging examinations, if necessary. For example, the model took into account that a proportion of patients cannot undergo MR angiography because of contraindications, in which case the patients undergo DSA.

Another limitation of the study was that we did not consider regional health care circumstances such as the expertise of the radiologists and the availability of equipment. In an earlier study (25), it was found that differences in quality-adjusted life expectancy and lifetime costs among diagnostic imaging modalities were small, and a new imaging modality that enabled the target values to be met would be in the same range as MR angiography, duplex US, and DSA.

To determine the cost-effectiveness of a new imaging modality that fulfills the target criteria assessed in the current study, it might be better to compare CT angiography with the currently used work-up modality in a pragmatic empirical setting. Such a comparison could be made in a randomized controlled trial in which patients are randomly placed in either the new imaging modality group or the currently used work-up modality group (45) and followed up for a certain time. Possible outcome measures would be the quality of life of the patients, the costs incurred by performing the work-up imaging examination, including those for supplementary imaging and treatment, the confidence of the physician in the examination result, and the patients’ and/or the physicians’ preferred imaging modalities. This suggested study design would also take into account local expertise, physicians’ preferences, and equipment availability.

A final limitation was that we assumed that the society’s willingness to pay (ie, amount of money society is willing to pay for one additional QALY) could be defined. The amount society is willing to pay depends on many variables, such as the characteristics of the health care system, the general economy, and the decision context. The actual value is always hypothetical. Recently, an attempt to estimate society’s willingness to pay was made by converting estimates of value of life, which were available from various sources, to dollars per QALY gained (46). A range of willingness-to-pay values, from $25,000 to $428,000 per QALY (in 1997 U.S. dollars), was observed (46).

In our base-case analysis, we used $100,000 per QALY as an estimate of society’s willingness to pay. We performed an extensive sensitivity analysis and found that the results did not change substantially when society’s willingness to pay was varied (from $50,000 to $250,000/QALY gained). We chose $100,000 per QALY as a baseline value instead of the commonly quoted $50,000 per QALY for various reasons: First, the incremental cost-effectiveness ratios for generally accepted interventions vary between $10,000 and $100,000 per QALY gained (47), indicating that the threshold should be $100,000 per QALY. Second, a willingness to pay of $50,000 per QALY has been quoted for well over 10 years and to our knowledge has not been adjusted for either inflation or increasing levels of welfare use. Third, we wanted to determine the least stringent target values that would need to be met for a new technology, and the use of a high threshold value yields the least stringent target criteria.

Currently, several new imaging techniques have been suggested for use in the work-up of patients with PAD (16–21,48–50). The most promising of these techniques seems to be multi–detector row CT angiography, which is simple to perform, fast, and quickly becoming widely available. Preliminary results indicate that multi–detector row CT angiography has high diagnostic accuracy and a sensitivity close to our estimated target value (17,48–50). The cost of a contrast material–enhanced CT angiography examination was estimated to be $237 (in 1997 U.S. dollars) (51), which was below the target cost. The fact that CT angiography depicts the calcified vessel wall is a disadvantage because the appearance of calcium interferes with the accurate interpretation of stenosis severity and thus may necessitate additional work-up.

On the other hand, contraindications to CT angiography are rare. Usually, a low-osmolality contrast material is used to perform CT angiography, and a small degree of risk associated with the use of contrast material was incorporated into our analysis. The long-term risks of radiation were not considered in our analysis. However, the risk of a one-time exposure is low, and the life expectancy of most patients who have PAD is shorter than the time it typically takes to develop long-term harmful effects from radiation.

In conclusion, compared with currently used imaging examinations such as MR angiography, multi–detector row CT angiography has the potential to be cost-effective in the evaluation of patients with intermittent claudication. The role of new imaging modalities that have fairly good preliminary results can be assessed by performing a pragmatic randomized controlled trial in which the new modality is compared with the imaging modality that is currently being used for diagnostic work-up.


   FOOTNOTES
 
Abbreviations: DSA = digital subtraction angiography, PAD = peripheral arterial disease, QALY = quality-adjusted life year

Author contributions: Guarantor of integrity of entire study, M.G.M.H.; study concepts, all authors; study design, K.V., M.C.J.M.K., M.G.M.H.; literature research, K.V., M.C.J.M.K.; data acquisition, K.V.; data analysis/interpretation, all authors; statistical analysis, K.V.; manuscript preparation, K.V.; manuscript definition of intellectual content, all authors; manuscript editing, K.V.; manuscript revision/review and final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

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