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Decision analysis of cost-effectiveness of magnetic resonance angiography for mass screening for intracranial aneurysms
Decision Analysis of Cost-Effectiveness of Magnetic Resonance Angiography for Mass Screening for Intracranial Aneurysms Yuji Baba, MD, Mutsumasa Takahashi, MD, Yukunori Korogi, MD
The morbidity (50%) and mortality (25%) associated with subarachnoid hemorrhage due to the rupture of Cerebral aneurysms remain high in spite of modern advances in management (1-3). Surgical treatment of unruptured intracranial aneurysms, on the other hand, has a relatively low risk of serious complications and death (1,4,5). In Japan, therefore, mass screening has been advocated to detect asymptomatic unruptured cerebral aneurysms before major hemorrhage occurs (6,7). Because MR angiography is noninvasive and free from radiation-induced risks, trials of the feasibility of using MR angiography for mass screening are under way in many hospitals and clinics in Japan (8). The purpose of this study is to apply a cost-effectiveness analysis to such a feasibility study.
MIRAscreening;spontaneousruptureof ansurysms
.•No
MRA
y MRAdeath
screening 7
F - No aneurysm(truenegative) MRA negative I~-'L- Aneurysmpresent(false negative); I_~ spontaneousrupture L MP~ ~ ' - c- Angiodeath posihve ~- c-Angiocomplication II c-Angionegative(false positive)
F
I_~
c-Anglopositiver - Nosurgery (truepositive) -~_ [-Surg-death SurgeryT Surg-complication ~ - Nocomplication
Figure1.
Decision tree for analysis of MR angiography for mass screening for cerebral aneurysm (arm 1 [upper] = without MR angiography; arm 2 (lower] = with MR angiography and operation of unruptured aneurysms).
Prevalence and Incidence of Unruptured and Ruptured Cerebral Aneurysms Clinical benefit and cost-effectiveness of MR angiography for mass screening of intracranial aneurysms were evaluated by using a decision-analysis method. Figure 1 illustrates the decision tree of the analysis. The rate of death and the rate of complications, as well as the cost to save a life, were calculated with and without MR angiography screening. The following parameters were used in the analysis: prevalence and incidence of unruptured and ruptured cerebral aneurysms, diagnostic accuracy of MR angiography, complications of conventional angiography, surgical treatment of unruptured aneurysms, and costs of interventions.
Acad Radio11998; 5(suppl 2):$297-$299
1From the Department of Radiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860, Japan, Address reprint requests to Y,B,
©AUR, 1998
The prevalence of unruptured cerebral aneurysms has been reported from autopsy and cerebral angiography to be 2%-5% (9,10). Incidence rises with advancing age and is lower when a large number of young persons are included in the subject group. An incidence rate of 2%, however, is an appropriate estimate for the general population. The reported rate of rupture of cerebral aneurysms varies considerably (11-13). In patients with one aneurysm clipped and the other left untouched, the rupture rate is 1%-2% annually (11-13). Approximately 2% is a good estimate of the rupture rate per year, a statistic that corresponds roughly to the number of subarachnoid hemorrhages in the general population. The rates of death and permanent complication induced by an aneurysmal rupture are estimated to be 0.5% and 0.25%, respectively (3).
Diagnostic Accuracy of MR Angiography The most important factor in evaluating the feasibility of mass screening with MR angiography is its accuracy in detecting cerebral aneurysms. A special committee of the
$297
3ABA ET AL
Vol 5, Suppl 2, S e p t e m b e r 199t
cost(yen)/life save
life save complication
¥175,000,000 0.003
.................................................................................
¥150,000,000 ¥I
ZS,O00,O00
O.OOZ ¥100,000,000
¥75,000,000
0.001 ¥50,000,000 ¥Z5,000,000
0
¥0 o
-0.001
,o
;5
2o
follow up (yr)
0
I
I
I
I
S
10
15
ZO
follow up (yr) Figure 2. Life save a n d c o m p l i c a t i o n rates by follow-up year (life save rate = A; c o m p l i c a t i o n rate = @; and life save plus c o m p l i c a t i o n rate = m). Complication rate is higher than natural course ( i m p r o v e m e n t of c o m p l i c a t i o n rate is negative) until 18 years of follow-up. Life save + c o m p l i c a tion is negative until 6 years of follow-up.
Japanese Society of Magnetic Resonance in Medicine conducted two retrospective studies (using 131 patients and 203 patients, respectively) analyzing the diagnostic accuracy of MR angiography for mass screening for cerebral aneurysms. With specificity set at 80%, sensitivity for the detection of one aneurysm ranged from 64% to 87% on MIP and source images (14-16). Other studies have found specificity and sensitivity of MR angiography to be 80% and 87%, respectively.
Complications of Conventional Angiography Numerous reports of complications associated with cerebral angiography have been published. The incidence of permanent neurologic deficits has been reported to be 0.2%-5.7% (17-21). According to the report by Waugh and Sacharias (17), who used digital subtraction angiography and a nonionic contrast medium, the incidence of permanent neurologic complications was 0.3%, and the incidence of fatal complications was 0.1% or less. In this study, mortality and morbidity are reported to be 0.0001% and 0.3%, respectively. Surgery of Unruptured Aneurysms Unruptured aneurysms can be treated surgically with a low complication rate (1,4,5); the rates of fatal complications and permanent neurologic complications have been reported to be 0.1% and 0.4%, respectively.
$298
;
Figure 3.
Cost t o s a v e a life. Cost t o s a v e a life with sensitivity a n d specificity rates of 95% a n d 90% (m) a n d 87% a n d 80% (0). Even with high (95% sensitivity, 90% specificity), diagnostic a c c u r a c y the cost to save a life is very high, even at 10 years of follow-up (more than $200,000).
Costs Costs of MR angiography, conventional angiography, operation of unruptured aneurysms, and treatment of ruptured aneurysms have been reported to be 25,000 yen, 8,000 yen, 1,000,000 yen, and 5,000,000 yen, respectively.
Lives Saved Figure 2 shows that at a 5-year follow-up, the estimated rates of lives saved and complications were 64 per 100,000 and 92 per 100,000, respectively. The rate of complications is higher than the natural course (ie, improvement in the complication rate is negative) until 18 years after the intervention. Lives saved plus complications in the mass-screening group was estimated to be worse than the natural course until 6 years after the intervention. Cost to Save a Life Figure 3 shows the estimated cost to save a life in two constructs, one with sensitivity and specificity assumed to be 87% and 80%, respectively, and another with sensitivity and specificity assumed to 95% and 90%, respectively. In the model using sensitivity of 87% and specificity of 80%, the cost to save a life was estimated to be 79,768,830 yen (about $690,000) at 5-year follow-up, and 31,170,312 yen (about $270,000) at 10-year follow-up. In comparison
with mass screening for lung cancer, the ratio of the cost to save a life is about 7:3. The results of this analysis indicate that mass screening for cerebral aneurysms with MR angiography is not costeffective at present. One problem is that the diagnostic accuracy of MR angiography for cerebral anem-ysms is approximately 80% specificity and 87% sensitivity. Therefore, patients undergoing screening for aneurysms with MR angiography need further examination with conventional angiography. Unfortunately, with conventional angiography there is a risk of neurologic complications (0.3%) as well as fatality (under 0.1%.) Another disadvantage of MR angiographic screening is that the natural history of cerebral aneurysms has not been clearly delineated. The possibility of de novo aneurysms has been suggested, but there are no published clinical data to support this hypothesis. Because the rupture rate of cerebral aneurysms is relatively low, approximately 1%-2%, a considerable proportion of aneurysms never rupture during the patient' s lifetime. Overall, it appears that at present the costs of MR studies, conventional angiography, and surgery, in addition to the relatively high complication rate, make mass screening with MR angiography infeasible. Randomized, controlled trials should be undertaken, however, to establish the true cost-effectiveness of such a program. Of course, patients should be informed of the details of mass screening, including the natural history of cerebral aneurysms, the diagnostic accuracy of MR angiography, and complications associated with cerebral angiography and surgery. Even though mass screening may not be practical, screening in certain high-risk groups may be more appropriate. For instance, the incidence of cerebral aneurysm is considerably higher in asymptomatic individuals who have a family history of subarachnoid hemorrhage. In such populations, screening may be justified to detect unruptured aneurysms before a major catastrophic event occurs. In addition, patients with polycystic kidney disease, fibromuscular dysplasia, and severe atherosclerotic disease of other vessels may be candidates for screening of cerebral aneurysms with MR angiography (22). As technologic improvements allow better MR diagnostic accuracy and conventional angiography is not required for surgery, screening programs may be more likely to be accepted.
REFERENCE.(
1. Kassell NF, Tomer JC. Size of intracranial aneurysms. Neurosurgery 1983; 12:291-297. 2. Bonita R, Thomson S. Subarachnoid hemorrhage: epidemiology, diagnosis, management, and outcome. Stroke 1985; 16:591-594. 3. Nakagawa T, Hashi K. The incidence and treatment of asymptomatic, unruptured cerebral aneurysms. J Neurosurg 1994; 80:217-223. 4. Wirth FP, Laws ER Jr, Piepgras D, Scott RM. Surgical treatment of incidental intracranial aneurysms. Neurosurgery 1983; 12:507-511. 5. Heiskanen O. Risksof surgery for unruptured intracranial aneurysms. J Neurosurg 1986; 65:451-453. 6. Schievink WI, Limburg M, Dreissen JJR, Peeters FLM, ter Berg HWM. Screening for unruptured familial intracranial aneurysms: subarachnoid hemorrhage 2 years after angiography negative for aneurysms. Neurosurgery 1991; 29:434-438. 7. Phillips LH, Whisnant JP, O'Fallon WM, Sundt TM Jr. The unchanging pattern of subarachnoid hemorrhage in a community. Neurology 1980; 30:1034-1040. 8. Takahashi M. Cost-effectiveness of magnetic resonance angiography for mass screening for intracranial aneurysms. Acad Radiol 1996; 3(suppl):40-43. 9. Wiebers DO, Torner JC, Meissner I. Impact of unruptured intracranial aneurysms on public health in the United States. Stroke 1992; 23:1416-1419.9, 10. Sekhar LN, Heros RC, Origin, growth, and rupture of saccular aneurysms: a review. Neurosurgery 1981; 8:248-260. 11. Winn HR, Almaasi WS, Berga SL, Jane JA, Richardson AE. The long-term outcome in patients with multiple aneurysms. J Neurosurg 1983; 59:642-651. 12. Heiskanen O. Risk of bleeding from unruptured aneurysms in cases with multiple intracranial aneurysms. J Neurosurg 1981; 55:524-526. 13. Jane JA, Kassell NF, Tomer JC, Winn HR, The natural history of aneurysms and arteriovenous malformations. J Neurosurg 1985; 62:321-323. 14. Korogi Y, Takahashi M, Mabuchi N, et al. Intracranial aneurysms: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography. Radiology 1994; 193:181-186. 15. Korogi Y, Takahashi M, Mabuchi N, et al, Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography. Radiology 1994; 193:187-193. 16. Korogi Y, Takahashi M, O'Uchi T, et al. Diagnostic accuracy of 3DFT time-of-flight MR angiography for intracranial aneurysms and steno-occlusive diseases: report on 1994 study (Fourth Report of Special Committee). Jpn J Magn Reson Med 1994; 14:415-421. 17. Waugh JR, Sacharias N. Arteriographic complications in the DSA era. Radiology 1992; 182:243-246. 18. Dion JF, Gates PC, Fox A J, Barneff HJM, BIom RJ. Clinical events following neuroangiography: a prospective study. Stroke 1987; 18:997-1004.
19. Hankey G J, Warlow CP, Sellar RJ. Cerebral angiographic risk in mild cerebrovascular disease. Stroke 1990; 21:209-222. 20. Olivecrona H. Complications of cerebral angiography. Neuroradiology 1977; 14:175-181. 21, Mclvor J, Steiner TJ, Perkin GD, Greenhalgh RM, Rose FC. Neurological morbidity of arch and carotid arteriography in cerebrovascular disease: the influence of contrast medium and radiologist. BrJ Radio11987; 60:117-122. 22. Ruggieri PM, Poulos N, Masaryk TJ, et al. Occult intracranial aneurysms in polycystic kidney disease: screening with MR angiography. Radiology 1994; 191;33-39,
$299
The morbidity (50%) and mortality (25%) associated with subarachnoid hemorrhage due to the rupture of Cerebral aneurysms remain high in spite of modern advances in management (1-3). Surgical treatment of unruptured intracranial aneurysms, on the other hand, has a relatively low risk of serious complications and death (1,4,5). In Japan, therefore, mass screening has been advocated to detect asymptomatic unruptured cerebral aneurysms before major hemorrhage occurs (6,7). Because MR angiography is noninvasive and free from radiation-induced risks, trials of the feasibility of using MR angiography for mass screening are under way in many hospitals and clinics in Japan (8). The purpose of this study is to apply a cost-effectiveness analysis to such a feasibility study.
MIRAscreening;spontaneousruptureof ansurysms
.•No
MRA
y MRAdeath
screening 7
F - No aneurysm(truenegative) MRA negative I~-'L- Aneurysmpresent(false negative); I_~ spontaneousrupture L MP~ ~ ' - c- Angiodeath posihve ~- c-Angiocomplication II c-Angionegative(false positive)
F
I_~
c-Anglopositiver - Nosurgery (truepositive) -~_ [-Surg-death SurgeryT Surg-complication ~ - Nocomplication
Figure1.
Decision tree for analysis of MR angiography for mass screening for cerebral aneurysm (arm 1 [upper] = without MR angiography; arm 2 (lower] = with MR angiography and operation of unruptured aneurysms).
Prevalence and Incidence of Unruptured and Ruptured Cerebral Aneurysms Clinical benefit and cost-effectiveness of MR angiography for mass screening of intracranial aneurysms were evaluated by using a decision-analysis method. Figure 1 illustrates the decision tree of the analysis. The rate of death and the rate of complications, as well as the cost to save a life, were calculated with and without MR angiography screening. The following parameters were used in the analysis: prevalence and incidence of unruptured and ruptured cerebral aneurysms, diagnostic accuracy of MR angiography, complications of conventional angiography, surgical treatment of unruptured aneurysms, and costs of interventions.
Acad Radio11998; 5(suppl 2):$297-$299
1From the Department of Radiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860, Japan, Address reprint requests to Y,B,
©AUR, 1998
The prevalence of unruptured cerebral aneurysms has been reported from autopsy and cerebral angiography to be 2%-5% (9,10). Incidence rises with advancing age and is lower when a large number of young persons are included in the subject group. An incidence rate of 2%, however, is an appropriate estimate for the general population. The reported rate of rupture of cerebral aneurysms varies considerably (11-13). In patients with one aneurysm clipped and the other left untouched, the rupture rate is 1%-2% annually (11-13). Approximately 2% is a good estimate of the rupture rate per year, a statistic that corresponds roughly to the number of subarachnoid hemorrhages in the general population. The rates of death and permanent complication induced by an aneurysmal rupture are estimated to be 0.5% and 0.25%, respectively (3).
Diagnostic Accuracy of MR Angiography The most important factor in evaluating the feasibility of mass screening with MR angiography is its accuracy in detecting cerebral aneurysms. A special committee of the
$297
3ABA ET AL
Vol 5, Suppl 2, S e p t e m b e r 199t
cost(yen)/life save
life save complication
¥175,000,000 0.003
.................................................................................
¥150,000,000 ¥I
ZS,O00,O00
O.OOZ ¥100,000,000
¥75,000,000
0.001 ¥50,000,000 ¥Z5,000,000
0
¥0 o
-0.001
,o
;5
2o
follow up (yr)
0
I
I
I
I
S
10
15
ZO
follow up (yr) Figure 2. Life save a n d c o m p l i c a t i o n rates by follow-up year (life save rate = A; c o m p l i c a t i o n rate = @; and life save plus c o m p l i c a t i o n rate = m). Complication rate is higher than natural course ( i m p r o v e m e n t of c o m p l i c a t i o n rate is negative) until 18 years of follow-up. Life save + c o m p l i c a tion is negative until 6 years of follow-up.
Japanese Society of Magnetic Resonance in Medicine conducted two retrospective studies (using 131 patients and 203 patients, respectively) analyzing the diagnostic accuracy of MR angiography for mass screening for cerebral aneurysms. With specificity set at 80%, sensitivity for the detection of one aneurysm ranged from 64% to 87% on MIP and source images (14-16). Other studies have found specificity and sensitivity of MR angiography to be 80% and 87%, respectively.
Complications of Conventional Angiography Numerous reports of complications associated with cerebral angiography have been published. The incidence of permanent neurologic deficits has been reported to be 0.2%-5.7% (17-21). According to the report by Waugh and Sacharias (17), who used digital subtraction angiography and a nonionic contrast medium, the incidence of permanent neurologic complications was 0.3%, and the incidence of fatal complications was 0.1% or less. In this study, mortality and morbidity are reported to be 0.0001% and 0.3%, respectively. Surgery of Unruptured Aneurysms Unruptured aneurysms can be treated surgically with a low complication rate (1,4,5); the rates of fatal complications and permanent neurologic complications have been reported to be 0.1% and 0.4%, respectively.
$298
;
Figure 3.
Cost t o s a v e a life. Cost t o s a v e a life with sensitivity a n d specificity rates of 95% a n d 90% (m) a n d 87% a n d 80% (0). Even with high (95% sensitivity, 90% specificity), diagnostic a c c u r a c y the cost to save a life is very high, even at 10 years of follow-up (more than $200,000).
Costs Costs of MR angiography, conventional angiography, operation of unruptured aneurysms, and treatment of ruptured aneurysms have been reported to be 25,000 yen, 8,000 yen, 1,000,000 yen, and 5,000,000 yen, respectively.
Lives Saved Figure 2 shows that at a 5-year follow-up, the estimated rates of lives saved and complications were 64 per 100,000 and 92 per 100,000, respectively. The rate of complications is higher than the natural course (ie, improvement in the complication rate is negative) until 18 years after the intervention. Lives saved plus complications in the mass-screening group was estimated to be worse than the natural course until 6 years after the intervention. Cost to Save a Life Figure 3 shows the estimated cost to save a life in two constructs, one with sensitivity and specificity assumed to be 87% and 80%, respectively, and another with sensitivity and specificity assumed to 95% and 90%, respectively. In the model using sensitivity of 87% and specificity of 80%, the cost to save a life was estimated to be 79,768,830 yen (about $690,000) at 5-year follow-up, and 31,170,312 yen (about $270,000) at 10-year follow-up. In comparison
with mass screening for lung cancer, the ratio of the cost to save a life is about 7:3. The results of this analysis indicate that mass screening for cerebral aneurysms with MR angiography is not costeffective at present. One problem is that the diagnostic accuracy of MR angiography for cerebral anem-ysms is approximately 80% specificity and 87% sensitivity. Therefore, patients undergoing screening for aneurysms with MR angiography need further examination with conventional angiography. Unfortunately, with conventional angiography there is a risk of neurologic complications (0.3%) as well as fatality (under 0.1%.) Another disadvantage of MR angiographic screening is that the natural history of cerebral aneurysms has not been clearly delineated. The possibility of de novo aneurysms has been suggested, but there are no published clinical data to support this hypothesis. Because the rupture rate of cerebral aneurysms is relatively low, approximately 1%-2%, a considerable proportion of aneurysms never rupture during the patient' s lifetime. Overall, it appears that at present the costs of MR studies, conventional angiography, and surgery, in addition to the relatively high complication rate, make mass screening with MR angiography infeasible. Randomized, controlled trials should be undertaken, however, to establish the true cost-effectiveness of such a program. Of course, patients should be informed of the details of mass screening, including the natural history of cerebral aneurysms, the diagnostic accuracy of MR angiography, and complications associated with cerebral angiography and surgery. Even though mass screening may not be practical, screening in certain high-risk groups may be more appropriate. For instance, the incidence of cerebral aneurysm is considerably higher in asymptomatic individuals who have a family history of subarachnoid hemorrhage. In such populations, screening may be justified to detect unruptured aneurysms before a major catastrophic event occurs. In addition, patients with polycystic kidney disease, fibromuscular dysplasia, and severe atherosclerotic disease of other vessels may be candidates for screening of cerebral aneurysms with MR angiography (22). As technologic improvements allow better MR diagnostic accuracy and conventional angiography is not required for surgery, screening programs may be more likely to be accepted.
REFERENCE.(
1. Kassell NF, Tomer JC. Size of intracranial aneurysms. Neurosurgery 1983; 12:291-297. 2. Bonita R, Thomson S. Subarachnoid hemorrhage: epidemiology, diagnosis, management, and outcome. Stroke 1985; 16:591-594. 3. Nakagawa T, Hashi K. The incidence and treatment of asymptomatic, unruptured cerebral aneurysms. J Neurosurg 1994; 80:217-223. 4. Wirth FP, Laws ER Jr, Piepgras D, Scott RM. Surgical treatment of incidental intracranial aneurysms. Neurosurgery 1983; 12:507-511. 5. Heiskanen O. Risksof surgery for unruptured intracranial aneurysms. J Neurosurg 1986; 65:451-453. 6. Schievink WI, Limburg M, Dreissen JJR, Peeters FLM, ter Berg HWM. Screening for unruptured familial intracranial aneurysms: subarachnoid hemorrhage 2 years after angiography negative for aneurysms. Neurosurgery 1991; 29:434-438. 7. Phillips LH, Whisnant JP, O'Fallon WM, Sundt TM Jr. The unchanging pattern of subarachnoid hemorrhage in a community. Neurology 1980; 30:1034-1040. 8. Takahashi M. Cost-effectiveness of magnetic resonance angiography for mass screening for intracranial aneurysms. Acad Radiol 1996; 3(suppl):40-43. 9. Wiebers DO, Torner JC, Meissner I. Impact of unruptured intracranial aneurysms on public health in the United States. Stroke 1992; 23:1416-1419.9, 10. Sekhar LN, Heros RC, Origin, growth, and rupture of saccular aneurysms: a review. Neurosurgery 1981; 8:248-260. 11. Winn HR, Almaasi WS, Berga SL, Jane JA, Richardson AE. The long-term outcome in patients with multiple aneurysms. J Neurosurg 1983; 59:642-651. 12. Heiskanen O. Risk of bleeding from unruptured aneurysms in cases with multiple intracranial aneurysms. J Neurosurg 1981; 55:524-526. 13. Jane JA, Kassell NF, Tomer JC, Winn HR, The natural history of aneurysms and arteriovenous malformations. J Neurosurg 1985; 62:321-323. 14. Korogi Y, Takahashi M, Mabuchi N, et al. Intracranial aneurysms: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography. Radiology 1994; 193:181-186. 15. Korogi Y, Takahashi M, Mabuchi N, et al, Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography. Radiology 1994; 193:187-193. 16. Korogi Y, Takahashi M, O'Uchi T, et al. Diagnostic accuracy of 3DFT time-of-flight MR angiography for intracranial aneurysms and steno-occlusive diseases: report on 1994 study (Fourth Report of Special Committee). Jpn J Magn Reson Med 1994; 14:415-421. 17. Waugh JR, Sacharias N. Arteriographic complications in the DSA era. Radiology 1992; 182:243-246. 18. Dion JF, Gates PC, Fox A J, Barneff HJM, BIom RJ. Clinical events following neuroangiography: a prospective study. Stroke 1987; 18:997-1004.
19. Hankey G J, Warlow CP, Sellar RJ. Cerebral angiographic risk in mild cerebrovascular disease. Stroke 1990; 21:209-222. 20. Olivecrona H. Complications of cerebral angiography. Neuroradiology 1977; 14:175-181. 21, Mclvor J, Steiner TJ, Perkin GD, Greenhalgh RM, Rose FC. Neurological morbidity of arch and carotid arteriography in cerebrovascular disease: the influence of contrast medium and radiologist. BrJ Radio11987; 60:117-122. 22. Ruggieri PM, Poulos N, Masaryk TJ, et al. Occult intracranial aneurysms in polycystic kidney disease: screening with MR angiography. Radiology 1994; 191;33-39,
$299