Economic evaluations of diagnostic and screening strategies for pulmonary embolism
| Study . | Country/setting . | Study design/analytic technique . | Perspective . | Time horizon/discount . | Currency/y . | Population/pretest probability (prevalence) . | Intervention and comparison . | Results . |
|---|---|---|---|---|---|---|---|---|
| d-dimer | ||||||||
| Blondon 2020 | Multiple countries; inpatient and outpatient | Decision analytic model (decision tree);cost utility analysis | Health care system | Lifetime horizon;3% for both cost and effectiveness | $ (USD) in 2018 | Hypothetical cohort of patients with suspected PE with a non-high pretest probability; non-high pretest probability | Age-adjusted d-dimer strategy compared with standard d-dimer strategy | When Geneva risk score was used, compared with the standard cutoff, the age-adjusted d-dimer test cutoff was associated with a loss of 0.0001 quality-adjusted life-years (16.076 QALYs vs 16.076 QALYs) and an average cost reduction of $33.4 ($1562 for age-adjusted d-dimer test vs $1596 for standard d-dimer test). When Wells risk score was used, the cost-effectiveness results were similar to Geneva risk score. The age-adjusted d-dimer test cutoff results in a clinically nonsignificant decrease in QALY but important costs reductions. |
| Duriseti 2006 | USA; an urban emergency department | Decision analytic model; cost utility analysis | Unclear | 25 y (lifetime for a 55-y-old patient);3% for both cost and effectiveness | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism; all patients, unselected, prevalence unknown | The d-dimer test was combined with 10 imaging strategies: (1) no imaging; (2) compression ultrasound alone; (3) compression ultrasound followed by V/Q if negative, and treatment if V/Q > low; (4) compression ultrasound followed by V/Q if negative, and treatment if V/Q > normal; (5) compression ultrasound treatment if V/Q > intermediate; (6) V/Q and treatment if V/Q > low; 7)V/Q and treatment if V/Q > normal; (8) V/Q and treatment if V/Q > intermediate; (9) CT angiogram and treatment if CT angiogram positive; and (10) compression ultrasound followed by CTP (CT angiogram with pulmonary portion) with treatment if either test is positive | In the base case, for all patient pretest categories, the most cost-effective diagnostic strategy is to use an initial enzyme-linked immunosorbent assay d-dimer test, followed by compression ultrasound of the lower extremities if the d-dimer is above a specified cutoff. |
| Duriseti 2010 | USA; emergency department | Decision analytic model; cost utility analysis | Not reported (indirect cost considered) | 25 y (lifetime for a 55-y-old patient);3% for both cost and effectiveness | $ (USD), currency year not specified | Hypothetical patients presenting with undifferentiated symptoms suggestive of pulmonary embolism; all patients, unselected, prevalence unknown | The d-dimer test was combined with 10 imaging strategies: (1) no imaging; (2) compression ultrasound alone; (3) compression ultrasound followed by V/Q if negative, and treatment if V/Q > low; (4) compression ultrasound followed by V/Q if negative, and treatment if V/Q > normal; (5) compression ultrasound treatment if V/Q > intermediate; (6) V/Q and treatment if V/Q > low; (7)V/Q and treatment if V/Q > normal; (8) V/Q and treatment if V/Q > intermediate; (9) CT angiogram and treatment if CT angiogram positive; and (10) compression ultrasound followed by CTP (CT angiogram with pulmonary portion) with treatment if either test is positive | For all patient pretest categories, the best strategy is to use a d-dimer test, followed by compression ultrasound if the d-dimer is above a specified cutoff. A cutoff higher than the current widely used cutoff was preferred or dominant for all pretest categories except high Wells patients with clinically suspected deep venous thrombosis. |
| Elias 2004 | France; hospitalized patients | Decision analytic model; cost-effectiveness analysis | Health care payer’s perspective | 3 mo; no discount (time horizon ≤ 1 y) | € in 2011 | Hypothetical patients with suspected pulmonary embolism; prevalence from literature, not reported | The following strategies were compared: (1) V/Q, angiography; (2) d-dimer, limited bilateral ultrasound, V/Q scan-clinical probability, angiography; (3) d-dimer- clinical probability, V/Q scan, limited bilateral ultrasound, serial limited bilateral ultrasound, angiography; (4) limited bilateral ultrasound, helical CT, clinical probability, V/Q scan, pulmonary angiography; (5) helical CT, limited bilateral ultrasound; (6) d-dimer assays, limited bilateral ultrasound, helical CT; (7) d-dimer, extended bilateral ultrasound, helical CT; (8) limited bilateral ultrasound, helical CT; and (9) extended bilateral ultrasound, helical CT | Strategies including D-dimer and/or ultrasound followed by helical CT were less costly than those using V/Q scan and angiography. Three strategies were dominant, including strategies 6, 8, and 9. Strategy 6, “d-dimer assays, limited bilateral ultrasound, followed by helical CT” was most cost-saving but the least effective of the 3 dominant strategies. Strategy 9, “extended bilateral ultrasound, helical CT” improves survival at an acceptable extra cost per life saved compared with strategy 6. |
| Humphreys 2004 | USA; setting not specified | Decision analytic model (decision tree);cost minimization analysis | Medicare charges | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD) in 2003 | Hypothetical patients with suspected acute pulmonary embolism; unselected, prevalence unknown | The strategy with Wells score and d-dimer was compared with the standard approach using American Thoracic Society guideline with V/Q scan | Costs of testing using an algorithm based on Wells score and d-dimer ($216.52) was less than with a standard approach (American Thoracic Society guideline with V/Q scan, cost $538.62) for evaluating suspected acute pulmonary embolism. |
| Lee 2011 | USA; setting not specified | Decision analytic model (decision tree); Cost effectiveness analysis | Third-party payer perspective (the US government as the third-party payer) | 3 mo; No discount (time horizon ≤ 1 y) | $ (USD) in 2006 | Patients With a high, intermediate, or low clinical probability of pulmonary embolism; 28.4% overall (10%, 37%, 69% for low, intermediate, and high clinical probability groups) | The following strategies were compared: (1) V/Q scan then pulmonary angiography; (2) CT; (3) ultrasound then CT; (4) CT then ultrasound; (5) d-dimer then CT; (6) d-dimer then ultrasound then CT; (7) d-dimer then CT then ultrasound; (8) V/Q scan then CT d-dimer then V/Q scan then pulmonary angiography. | The strategy of D-dimer followed by CT was cost-effective and had the lowest cost per life saved for all patients suspected with pulmonary embolism (high, intermediate, low clinical probabilities). The conventional strategy including ventilation and perfusion lung scanning followed by pulmonary angiography or CT was not cost-effective. |
| Michel 1996 | Netherlands; large teaching hospitals in Amsterdam | Decision analytic model (decision tree);cost-effectiveness analysis | Not reported (only direct costs were considered) | 6 mo;5% for effectiveness when calculating QALYs | Fl. in October 1995 | 487 patients with clinically suspected pulmonary embolism; consecutive patients (unselected patients, prevalence unknown) | The Dutch consensus with V/Q scan was compared with alternative strategies consisted of d-dimer, clinical decision rule, and angiography. | The strategy with highest survival and leading to considerable savings subsequently included a V/Q scan, a clinical decision rule, a d-dimer test, a pulmonary angiography, and leg ultrasound. Patients with a high probability V/Q scan, an abnormal angiography, or leg ultrasound test are treated, whereas treatment is withheld in patients with a normal V/Q scan, a normal clinical decision rule, a negative d-dimer test, a normal angiography, or a normal leg ultrasound test. |
| Perrier 1997 | Switzerland; emergency department | Decision analytic model (decision tree);cost-effectiveness analysis | Health care system | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism;35% (intermediate risk) | The following strategies were compared: (1) no treatment; (2) lung scan then angiography (reference strategy for judging effectiveness); (3) lung scan followed by ultrasound then angiography; (4) lung scan followed by d-dimer and ultrasound then angiography; (5) d-dimer, followed by ultrasound then lung scan in case of a negative ultrasound, and angiography; (6) lung scan, no treatment of low probability, angiography for intermediate probability, treatment of high probability; (7) identical to strategy 5, except patients initially undergo a negative D-dimer or ultrasound do not undergo lung scan; and (8) d-dimer followed by ultrasound then scan, treatment except those with a normal or near-normal scan | The D-dimer test and ultrasound are cost-effective in the diagnosis of pulmonary embolism, whether performed after or before lung scan, thus avoiding costly referrals to lung scanning and/or angiography. For patients with a low clinical probability, a low-probability lung scan, and a normal ultrasound, treatment may be withheld without referring to angiography. |
| Perrier 2003 | Switzerland; tertiary care center in Geneva | Decision analytic model (decision tree);cost utility analysis | Third-party payer perspective | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 1996 | Hypothetical patients with suspected pulmonary embolism;10%, 37%, 69% for low, intermediate, and high clinical probability groups, respectively | The following strategies were compared: (1) V/Q scan ± angiography; (2) CT; (3) ultrasound ± CT; (4) d-dimer ± ultrasound ± CT; (5) d-dimer ± ultrasound ± CT ± angiography; (6) d-dimer ± ultrasound ± V/Q scan; (7) d-dimer ± ultrasound ± V/Q scan ± angiography; and (8) d-dimer ± ultrasound ± V/Q scan ± CT | For low clinical probability of pulmonary embolism patients, all strategies were reasonably effective, considering that the 3-mo survival remained within a range of 0.5% mortality compared with the reference strategy (V/Q scan ± angiography, $1728). The cheapest strategy was d-dimer ± ultrasound ± V/Q scan ($845), followed by d-dimer ± ultrasound ± CT ($1230). When clinical probability of pulmonary embolism was intermediate, the most cost-effective strategy was d-dimer ± ultrasound ± V/Q scan ± CT, in which a nondiagnostic V/Q scan is followed by helical CT ($2674). That strategy allowed us to forego pulmonary angiography in all patients. d-dimer ± ultrasound ± V/Q scan ± angiography was also cost saving compared with the reference strategy ($2832 vs $3164, respectively) and required an angiogram in 29% of patients. In patients with a high clinical probability of pulmonary embolism, d-dimer ± ultrasound ± V/Q scan ± CT remained the cheapest strategy ($4308) but was of marginal effectiveness (difference because of a higher proportion of patients treated unnecessarily, in 3-mo survival with the reference strategy, 0.47%). |
| Righini 2007 | Switzerland; emergency department | Decision analytic model (decision tree);cost utility analysis | Payer | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 2006 | 1721 consecutive patients with suspected pulmonary embolism; consecutive patients (unselected patients, prevalence unknown) | Four strategies were compared: (1) clinical probability ± d-dimer ± compression ultrasound ± helical CT; (2) clinical probability ± d-dimer ± helical CT; (3) clinical probability ± compression ultrasound ± helical CT; and (4) helical CT alone | All strategies were equally safe. Whatever the diagnostic strategy and whatever the age, the effectiveness remained very high, with variations in the 3-mo survival never exceeding 0.5% compared with the most effective strategy. Diagnostic strategies using d-dimer are less expensive. d-dimer measurement was highly cost-saving under the age of 80 y. |
| Van Beek 1996 | Netherlands; a secondary and tertiary referral center (both inpatient and outpatient) | Decision analytic model; cost-effectiveness analysis | Not reported (only direct costs were considered) | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | ECU, currency year not specified | 203 consecutive patients with suspected pulmonary embolism; consecutive patients (unselected patients, prevalence unknown) | The strategies compared include: (1) V/Q scan with ultrasound, if scan shows non-high probability and angiography, if ultrasound is normal; treatment if scan shows high probability, if ultrasound is abnormal, or if angiography shows pulmonary embolism; (2) d-dimer followed by strategy 1 if d-dimer elevated; (3) V/Q scan with d-dimer if scan shows non-high probability, ultrasound if d-dimer elevated and angiography if ultrasound is normal; treatment as strategy 1; (4) V/Q scan with angiography if scan shows non-high probability; treatment if scan shows high probability or if angiogram shows pulmonary embolism; (5) d-dimer followed by strategy 4 if d-dimer elevated; and (6) V/Q scan with d-dimer if scan shows non-high probability and angiography if d-dimer elevated; treatment as strategy 4 | Addition of the d-dimer assay to the diagnostic strategies does not result in any significant change in the mortality rates, whereas morbidity decreases to a slightly lower level. Addition of the d-dimer assay leads to an approximate 10% cost reduction in addition to a 25%-28% reduction in the number of patients requiring pulmonary angiography. |
| Van Erkel 1996 | Netherlands; a secondary and tertiary referral center | Decision analytic model (decision tree);cost-effectiveness analysis | Hospital | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism; 24% | Conventional angiographic strategies:(1) V/Q scanning, ultrasound, and conventional angiography; (2) ultrasound and conventional angiography; (3) V/Q scanning and conventional angiography; and (4) V/Q scanning, US, d-dimer assay, and conventional angiography. Spiral CT angiographic strategies:(5) spinal CT angiography; (6) ultrasound and spiral CT angiography; (7) perfusion scanning and spinal CT angiography; (8) perfusion scanning, US, and spiral CT angiography; (9) ultrasound, perfusion scanning, and spiral CT angiography; (10) V/Q scanning, ultrasound, and spiral CT angiography; (11) ultrasound, d-dimer assay, and spinal CT angiography; and (12) d-dimer assay and spiral CT angiography. Reference strategies:(13) no therapy; (14) therapy in all patients; and (15) ideal. | With the mortality or cost per life saved as the primary outcome parameter, the best strategies all included use of spiral CT angiography. Use of ultrasound before spiral CT angiography reduced the mortality but increased the cost per life saved ($20 562 per life saved vs $19 564 per life saved for spiral CT angiography only). The d-dimer test before spiral CT angiography increased the mortality but improved the marginal cost-effectiveness ($16 493 per life saved vs $19 564 per life saved for spiral CT angiography only). |
| Van Erkel 1998 | Netherlands; a secondary and tertiary referral center | Decision analytic model (decision tree);cost-effectiveness analysis | Hospital | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism;24% | CT strategies:(1) CT; (2) ultrasound and CT; (3) perfusion scan and CT; (4) perfusion scan, ultrasound, and CT; (5) ultrasound, perfusion scan, and CT; and (6) V/Q scan, ultrasound, and CT. PA strategies: (7) ultrasound and pulmonary angiography; and (8) V/Q scan, ultrasound, and pulmonary angiography. d-dimer/CT strategies: (9) d-dimer and CT; (10) d-dimer, ultrasound, and CT; (11) d-dimer, perfusion scan, and CT; (12) d-dimer, perfusion scan, ultrasound, and CT; (13) d-dimer, ultrasound, perfusion scan, and CT; (14) d-dimer, V/Q scan, ultrasound, and CT, d-dimer/pulmonary angiography strategies; (15) d-dimer, ultrasound, and pulmonary angiography; and (16) d-dimer, V/Q scan, ultrasound, and pulmonary angiography. Reference strategies:(17) no therapy; and (18) all therapy. | Strategies using helical CT have lower costs and higher survival than strategies that use pulmonary angiography. With a willing to pay threshold of $500 000 for each additional life saved, the most cost-effective strategy under baseline conditions is ultrasound followed by helical CT. Using this strategy, the average patient survival is 99.39% at an average cost of $1125 per patient, leading to an incremental cost-effectiveness of $116 000 per extra life saved when compared with the best strategy previously recommended (the same algorithm but preceded by the d-dimer test). |
| Van Erkel 1999 | Netherlands; European and United States hospitals | Decision analytic model (decision tree);cost-effectiveness analysis | Not reported (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | ECU in 1997 | Hypothetical patients with suspected pulmonary embolism;24%. | CT strategies:(1) CT; (2) ultrasound, CT; (3) perfusion scan, CT; (4) perfusion scan, Ultrasound, CT; (5) ultrasound, perfusion scan, CT; (6) V/Q scan, ultrasound, CT; (7) d-dimer and CT; (8) d-dimer, ultrasound, CT;( 9) d-dimer, perfusion scan, CT; (10) d-dimer, perfusion scan, ultrasound, CT; (11) d-dimer, ultrasound, perfusion scan, CT; and 12) d-dimer, V/Q scan, ultrasound, CT. PA strategies:(13) ultrasound, pulmonary angiography; (14) V/Q scan, ultrasound, pulmonary angiography; (15) d-dimer, ultrasound, pulmonary angiography; and 16) d-dimer, V/Q scan, ultrasound, pulmonary angiography. Reference strategies:(17) no therapy; and (18) all therapy. | The most cost-effective strategy was ultrasound followed by helical CT. |
| V/Q scan or CTPA | ||||||||
| Batalles 2009 | Argentina; inpatient | Decision analytic model (decision tree);cost-effectiveness analysis | Third-party payer perspective | A short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2008 | Hypothetical patient who was hospitalized for another diagnosis other than PTE presented with an episode of sudden dyspnea;28.4%. | The strategies compared included: (1) V/Q lung scan; (2) spiral CT; (3) angiography by MDCT; (4) MRI; and (5) conventional arteriography. | The most cost-effective diagnostic test was angiography by MDCT. Compared with V/Q scan, the cost per additional diagnosis of pulmonary embolism was €127.2 for spiral CT. Angiography by MDCT cost €2168.4 for each additional PE diagnosis compared with spiral CT. MRI and conventional arteriography were dominated by angiography by MDCT. |
| Doyle 2004 | USA; not specified | Decision analytic model (decision tree);cost-effectiveness analysis | Third-party payer perspective | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | 100 hypothetical pregnant women or women in the puerperium with clinical suspicion for PE;5%. | Diagnostic test for PE in pregnancy included: (1) compression ultrasound followed by anticoagulation (if there is a positive result) or secondary tests, V/Q scans or spiral CT (if there is a negative result); (2) V/Q scans as a primary test followed by anticoagulation; and (3) computed tomography followed by anticoagulation (if there is a positive result). | The use of spiral CT as the primary modality for the diagnosis of a suspected PE was the most cost-effective strategy at $17 208 per life saved vs the compression ultrasound strategy ($24 004 per life saved) and the V/Q scan strategy ($35 906 per life saved). If V/Q scanning or compression ultrasound scanning is used as the primary diagnostic modality, spiral CT is the most cost-effective secondary test; more cost-effective than V/Q scans or pulmonary angiography. |
| Henschke 1997 | USA; not specified | Not specified (likely decision analytic model);cost-benefit analysis | Patient | 6 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients suspected with pulmonary embolism; unselected. | The strategies compared included: (1) V/Q scan; (2) pulmonary arteriography; (3) MR angiography; and (4) CT angiography. | When the test charges are used, when the mortality is $1 and the morbidity is $10K, the best test is V/Q scan for prevalence rates below 10%. As mortality costs increase above $1, V/Q scan becomes the best algorithm for all prevalence values. When the mortality cost is $100K, V/Q is just slightly better than CT angiography or MR angiography. V/Q scan remains the best algorithm as the mortality costs increases. |
| Hull 1996 | Canada; Midwest urban hospital affiliated with a university medical school | Decision analysis; cost-effectiveness analysis | Third-party payer perspective | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD), Can$ in 1992 | 662 patients with suspected acute pulmonary embolism; consecutive patients (unselected patients, prevalence unknown). | The strategies compared included: (1) V/Q lung scans and pulmonary angiography; (2) V/Q lung scans, single noninvasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography; and (3) V/Q lung scans, serial noninvasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography. | For strategy 1, the charges in the United States for each patient who requires treatment would be $14 421, and the charges incurred per patient correctly withheld from treatment would be $5978. For strategy 2, the charges in the United States for each patient who requires treatment would be $14 047, and the charges incurred per patient correctly withheld from treatment would be $5865 if the noninvasive leg test was impedance plethysmography; and $14 407 and $6016 respectively, if the noninvasive leg test was Doppler ultrasound with B-mode imaging. For strategy 3, the charges in the United States for each patient who requires treatment would be $12 639, and the charges incurred per patient correctly withheld from treatment would be $4333 if the noninvasive leg test was impedance plethysmography; and $13 842 and $4745 respectively, if the noninvasive leg test was Doppler ultrasound with B-mode imaging. |
| Hull 2001 | Canada; Midwest urban hospital affiliated with a university medical school | Decision analysis; cost-effectiveness analysis | Third-party payer perspective | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | Can$ in 1999 | 662 patients with suspected acute pulmonary embolism; consecutive patients (unselected patients, prevalence unknown). | The strategies compared included: (1) V/Q lung scans and pulmonary angiography; (2) V/Q lung scans, single noninvasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography; and (3) V/Q lung scans, serial non-invasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography. | For strategy 1, the charges for each patient who requires treatment would be $10 761, and the charges incurred per patient correctly withheld from treatment would be $4461. For strategy 2, the charges for each patient who requires treatment would be $10 364, and the charges incurred per patient correctly withheld from treatment would be $4328. For strategy 3, the charges for each patient who requires treatment would be $8915, and the charges incurred per patient correctly withheld from treatment would be $3056. |
| Larcos 2000 | Australia; setting not specified | Decision analytic model (decision tree);cost-effectiveness analysis | Not reported (only direct costs were considered) | Lifetime horizon; life-years gained discounted: 3% | A$ in 1996/1997 | Hypothetical patients with suspected acute pulmonary embolism;34%. | The strategies compared included: (1) V/Q scan + ultrasound, pulmonary angiography; (2) CT scan alone; and (3) CT scan + ultrasound, pulmonary angiography. | The V/Q scan strategy was more effective (20.1 lives saved for every 1000 persons screened) and more costly (additional cost of A$315 per patient) compared with CT. The cost per life saved was A$940. If CT replaced V/Q scan in the screening, more lives could be saved (2.6 additional lives saved for every 1000 persons screened). Replacing V/Q scan with CT was also more costly (additional cost of A$979 per patient) compared with CT. The cost per life saved was A$23 905. |
| Muangman 2012 | Thailand; setting not specified | Prospective cohort; cost-effectiveness analysis | Not reported (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | ฿ currency year not specified | 100 cases with moderate to high probability for pulmonary embolism according to Wells criteria; moderate to high probability of pulmonary embolism. | Combined CTPA and indirect CTV was compared with strategy with sequential CTPA followed by direct CTV for negative PE cases. | The study found that 70 909 baht more per case for the combined CTPA and indirect CTV was needed for early detection of DVT (combined CTPA and indirect CTV: ฿3 744 000; sequential CTPA followed by direct CTV for negative PE cases: ฿2 964 000). |
| Oudkerk 1993 | Netherlands; inpatient | Decision analytic model; cost-effectiveness analysis | Unclear | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with clinically suspected pulmonary embolism;30%. | The strategies compared included: (1) no treatment; (2) no diagnostic test; treatment of all patients; (3) perfusion scan and treatment if scan is abnormal; (4) perfusion scan, followed with angiography if scan is abnormal, treatment if pulmonary embolism is shown; (5) V/Q scan, treatment only If scan shows high probability; (6) V/Q scan, followed with angiography if scan shows non-high probability, treatment if scan shows high probability or if angiography shows pulmonary embolism; (7) angiography in all patients, treatment if pulmonary embolism is shown; (8) ultrasound in all patients, followed with angiography if ultrasound is normal, treatment if ultrasound is abnormal or if angiography shows pulmonary embolism; (9) V/Q scan, followed with ultrasound if scan shows non high probability, treatment if scan shows high probability or if ultrasound is abnormal; and (10) V/Q scan, followed with ultrasound if scan shows non high probability and angiography if ultrasound is normal, treatment if scan shows high probability, if ultrasound is abnormal, or if angiography shows pulmonary embolism. | The analysis identified 3 categories of strategies. The first category included treatment of all patients (or of those with an abnormal perfusion scan). These strategies had the lowest mortality and morbidity rates but the highest costs because of inappropriate treatment of 55% to 70% of patients. The second category included pulmonary angiography strategies with or without prior V/Q lung scintigraphy and ultrasound of the legs had comparable low mortality and morbidity rates, lower rate of inappropriate treatment (fewer than 5% of patients). But it saved cost by about 40% compared with the first category. The third category used V/Q scintigraphy with or without ultrasound, and this category led to unacceptably high mortality rates. |
| Paterson 2001 | Canada; inpatient and outpatient | Decision analytic model (decision tree);cost-effectiveness analysis | Third-party payer perspective | 3 mo; no discount (time horizon ≤ 1 y) | Can$ in 1996 | Simulated cohort of 1000 patients with suspected acute pulmonary embolism, with a prevalence of 28.4% | The following strategies were compared: (1) spiral CT followed by ultrasound; (2) spiral CT followed by ultrasound and then angiography; (3) V/Q scan followed by ultrasound then angiography; (4) V/Q scan followed by ultrasound and then spiral CT; (5) spiral CT followed by angiography; (6) spiral CT alone; and (7) V/Q scan followed by spiral CT. | Four of the strategies yielded poorer survival at higher cost (strategies 2, 5, 6, and 7). The 3 remaining strategies were as follows: strategy 3, V/Q ± leg ultrasound ± pulmonary angiography (the “traditional” algorithm), with an expected survival of 953.7 per 1000 patients and a cost of $1416 per patient; strategy 4, V/Q scan followed by leg ultrasound and then spiral CT, with an expected survival of 953.4 per 1000 patients and a cost of $1391 per patient; strategy 1, spiral CT followed by leg ultrasound, with an expected survival of 958.2 per 1000 patients and a cost of $1751 per patient. Strategy 3 was then excluded by extended dominance. The cost per additional life saved was $70 833 for strategy 1 (spiral CT followed by leg ultrasound) relative to strategy 4 (V/Q scan followed by leg ultrasound then spiral CT). |
| Toney 2017 | USA; emergency department | Decision analytic model; cost-effectiveness analysis | Payer | 30 d; no discount (time horizon ≤ 1 y) | $ (USD) in 2016 | Hypothetical cohort of 1000 patients with suspected acute pulmonary embolism presenting to an emergency department;22.7%. | The strategies compared included: (1) single-photon emission CT; (2) single-photon emission CT with CT; (3) nuclear medicine; and (4) CT pulmonary angiography. | Total costs for 1000 patients were $3 638 078, $3 203 039, $5 768 844, and $3 824 694 for single-photon emission CT, single-photon emission CT with CT, nuclear medicine, and CT pulmonary angiography, respectively. Switching to single-photon emission CT with CT strategy yielding per-patient-per-month cost savings of $51.80 (vs CT pulmonary angiography), $213.80 (vs nuclear medicine), and $36.30 (vs single-photon emission CT). Total lives lost per 1000 patients was 28.90, 28.82, 31.21, and 34.34 for single-photon emission CT, single-photon emission CT with CT, nuclear medicine, and CT pulmonary angiography, respectively. |
| Ultrasound | ||||||||
| Beecham 1993 | USA; setting not specified | Retrospective medical data review; cost comparison | Not reported (only direct costs were considered) | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD) in 1993 | 223 consecutive patients suspected of pulmonary embolism; consecutive patients (unselected patients, prevalence unknown). | Pulmonary arteriography was compared with compression sonography plus pulmonary arteriography. | If all 145 patients whose lung scans were nondiagnostic had sonography and only those with normal sonograms had pulmonary arteriography, the professional and hospital charges would be $359 552. If all 145 had pulmonary arteriography without sonography, the charges would be $395 031. This study demonstrated that if V/Q lung scans indicated a low or an indeterminate probability of pulmonary embolism, only those patients with normal sonographic findings would need further study. |
| Ward 2011 | USA; emergency department | Decision analytic model (decision tree and Markov model);cost utility analysis | Societal | 6 mo;3% for effectiveness | $ (USD) in 2009 | Hypothetical 59 y old, hemodynamically stable female who presents with new-onset symptoms of pulmonary embolism;37.5%. | Selected CT (if ultrasound negative) was compared with universal CT strategy. | A selective CT strategy using compression US is cost-effective for patients with a high pretest probability of pulmonary embolism. The cost of universal CT strategy was $9051.94, whereas the cost was $7594.24 for a selective CT strategy. The selective CT strategy led to 0.0213 QALY gain compared with a universal CT strategy. |
| Other | ||||||||
| Goodacre 2018 | UK; UK National Health Service | Decision analytic model (decision tree);cost utility analysis | UK National Health Service and personal social service perspectives | Lifetime horizon;3.5% for both costs and benefits | £ in 2015/16 | Hypothetical pregnant or postpartum (up to 6 wk after birth) women who presented with a suspected pulmonary embolism at a UK hospital;6.5%. | The strategies compared included: (1) scanning all pregnant women with suspected pulmonary embolism (current recommended care); (2) applying the 3 expert-derived clinical consensus decision rules (primary, sensitive and specific); (3) applying a permissive interpretation of Wells’ decision rule (Wells’ permissive); (4) applying a strict interpretation of Wells’ decision rule (Wells’ strict); (5) applying the pulmonary embolism rule-out criteria decision rule; (6) applying the simplified Geneva decision rule; (7) scanning no women, but treating all; and (8) no scanning no treatment. | No scan, treat none, Wells’ score (strict), Delphi specificity score, Geneva score, Wells’ score (permissive), Delphi primary score, PERC score, no scan, treat all, Delphi sensitivity score all dominated by scan all. |
| Study . | Country/setting . | Study design/analytic technique . | Perspective . | Time horizon/discount . | Currency/y . | Population/pretest probability (prevalence) . | Intervention and comparison . | Results . |
|---|---|---|---|---|---|---|---|---|
| d-dimer | ||||||||
| Blondon 2020 | Multiple countries; inpatient and outpatient | Decision analytic model (decision tree);cost utility analysis | Health care system | Lifetime horizon;3% for both cost and effectiveness | $ (USD) in 2018 | Hypothetical cohort of patients with suspected PE with a non-high pretest probability; non-high pretest probability | Age-adjusted d-dimer strategy compared with standard d-dimer strategy | When Geneva risk score was used, compared with the standard cutoff, the age-adjusted d-dimer test cutoff was associated with a loss of 0.0001 quality-adjusted life-years (16.076 QALYs vs 16.076 QALYs) and an average cost reduction of $33.4 ($1562 for age-adjusted d-dimer test vs $1596 for standard d-dimer test). When Wells risk score was used, the cost-effectiveness results were similar to Geneva risk score. The age-adjusted d-dimer test cutoff results in a clinically nonsignificant decrease in QALY but important costs reductions. |
| Duriseti 2006 | USA; an urban emergency department | Decision analytic model; cost utility analysis | Unclear | 25 y (lifetime for a 55-y-old patient);3% for both cost and effectiveness | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism; all patients, unselected, prevalence unknown | The d-dimer test was combined with 10 imaging strategies: (1) no imaging; (2) compression ultrasound alone; (3) compression ultrasound followed by V/Q if negative, and treatment if V/Q > low; (4) compression ultrasound followed by V/Q if negative, and treatment if V/Q > normal; (5) compression ultrasound treatment if V/Q > intermediate; (6) V/Q and treatment if V/Q > low; 7)V/Q and treatment if V/Q > normal; (8) V/Q and treatment if V/Q > intermediate; (9) CT angiogram and treatment if CT angiogram positive; and (10) compression ultrasound followed by CTP (CT angiogram with pulmonary portion) with treatment if either test is positive | In the base case, for all patient pretest categories, the most cost-effective diagnostic strategy is to use an initial enzyme-linked immunosorbent assay d-dimer test, followed by compression ultrasound of the lower extremities if the d-dimer is above a specified cutoff. |
| Duriseti 2010 | USA; emergency department | Decision analytic model; cost utility analysis | Not reported (indirect cost considered) | 25 y (lifetime for a 55-y-old patient);3% for both cost and effectiveness | $ (USD), currency year not specified | Hypothetical patients presenting with undifferentiated symptoms suggestive of pulmonary embolism; all patients, unselected, prevalence unknown | The d-dimer test was combined with 10 imaging strategies: (1) no imaging; (2) compression ultrasound alone; (3) compression ultrasound followed by V/Q if negative, and treatment if V/Q > low; (4) compression ultrasound followed by V/Q if negative, and treatment if V/Q > normal; (5) compression ultrasound treatment if V/Q > intermediate; (6) V/Q and treatment if V/Q > low; (7)V/Q and treatment if V/Q > normal; (8) V/Q and treatment if V/Q > intermediate; (9) CT angiogram and treatment if CT angiogram positive; and (10) compression ultrasound followed by CTP (CT angiogram with pulmonary portion) with treatment if either test is positive | For all patient pretest categories, the best strategy is to use a d-dimer test, followed by compression ultrasound if the d-dimer is above a specified cutoff. A cutoff higher than the current widely used cutoff was preferred or dominant for all pretest categories except high Wells patients with clinically suspected deep venous thrombosis. |
| Elias 2004 | France; hospitalized patients | Decision analytic model; cost-effectiveness analysis | Health care payer’s perspective | 3 mo; no discount (time horizon ≤ 1 y) | € in 2011 | Hypothetical patients with suspected pulmonary embolism; prevalence from literature, not reported | The following strategies were compared: (1) V/Q, angiography; (2) d-dimer, limited bilateral ultrasound, V/Q scan-clinical probability, angiography; (3) d-dimer- clinical probability, V/Q scan, limited bilateral ultrasound, serial limited bilateral ultrasound, angiography; (4) limited bilateral ultrasound, helical CT, clinical probability, V/Q scan, pulmonary angiography; (5) helical CT, limited bilateral ultrasound; (6) d-dimer assays, limited bilateral ultrasound, helical CT; (7) d-dimer, extended bilateral ultrasound, helical CT; (8) limited bilateral ultrasound, helical CT; and (9) extended bilateral ultrasound, helical CT | Strategies including D-dimer and/or ultrasound followed by helical CT were less costly than those using V/Q scan and angiography. Three strategies were dominant, including strategies 6, 8, and 9. Strategy 6, “d-dimer assays, limited bilateral ultrasound, followed by helical CT” was most cost-saving but the least effective of the 3 dominant strategies. Strategy 9, “extended bilateral ultrasound, helical CT” improves survival at an acceptable extra cost per life saved compared with strategy 6. |
| Humphreys 2004 | USA; setting not specified | Decision analytic model (decision tree);cost minimization analysis | Medicare charges | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD) in 2003 | Hypothetical patients with suspected acute pulmonary embolism; unselected, prevalence unknown | The strategy with Wells score and d-dimer was compared with the standard approach using American Thoracic Society guideline with V/Q scan | Costs of testing using an algorithm based on Wells score and d-dimer ($216.52) was less than with a standard approach (American Thoracic Society guideline with V/Q scan, cost $538.62) for evaluating suspected acute pulmonary embolism. |
| Lee 2011 | USA; setting not specified | Decision analytic model (decision tree); Cost effectiveness analysis | Third-party payer perspective (the US government as the third-party payer) | 3 mo; No discount (time horizon ≤ 1 y) | $ (USD) in 2006 | Patients With a high, intermediate, or low clinical probability of pulmonary embolism; 28.4% overall (10%, 37%, 69% for low, intermediate, and high clinical probability groups) | The following strategies were compared: (1) V/Q scan then pulmonary angiography; (2) CT; (3) ultrasound then CT; (4) CT then ultrasound; (5) d-dimer then CT; (6) d-dimer then ultrasound then CT; (7) d-dimer then CT then ultrasound; (8) V/Q scan then CT d-dimer then V/Q scan then pulmonary angiography. | The strategy of D-dimer followed by CT was cost-effective and had the lowest cost per life saved for all patients suspected with pulmonary embolism (high, intermediate, low clinical probabilities). The conventional strategy including ventilation and perfusion lung scanning followed by pulmonary angiography or CT was not cost-effective. |
| Michel 1996 | Netherlands; large teaching hospitals in Amsterdam | Decision analytic model (decision tree);cost-effectiveness analysis | Not reported (only direct costs were considered) | 6 mo;5% for effectiveness when calculating QALYs | Fl. in October 1995 | 487 patients with clinically suspected pulmonary embolism; consecutive patients (unselected patients, prevalence unknown) | The Dutch consensus with V/Q scan was compared with alternative strategies consisted of d-dimer, clinical decision rule, and angiography. | The strategy with highest survival and leading to considerable savings subsequently included a V/Q scan, a clinical decision rule, a d-dimer test, a pulmonary angiography, and leg ultrasound. Patients with a high probability V/Q scan, an abnormal angiography, or leg ultrasound test are treated, whereas treatment is withheld in patients with a normal V/Q scan, a normal clinical decision rule, a negative d-dimer test, a normal angiography, or a normal leg ultrasound test. |
| Perrier 1997 | Switzerland; emergency department | Decision analytic model (decision tree);cost-effectiveness analysis | Health care system | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism;35% (intermediate risk) | The following strategies were compared: (1) no treatment; (2) lung scan then angiography (reference strategy for judging effectiveness); (3) lung scan followed by ultrasound then angiography; (4) lung scan followed by d-dimer and ultrasound then angiography; (5) d-dimer, followed by ultrasound then lung scan in case of a negative ultrasound, and angiography; (6) lung scan, no treatment of low probability, angiography for intermediate probability, treatment of high probability; (7) identical to strategy 5, except patients initially undergo a negative D-dimer or ultrasound do not undergo lung scan; and (8) d-dimer followed by ultrasound then scan, treatment except those with a normal or near-normal scan | The D-dimer test and ultrasound are cost-effective in the diagnosis of pulmonary embolism, whether performed after or before lung scan, thus avoiding costly referrals to lung scanning and/or angiography. For patients with a low clinical probability, a low-probability lung scan, and a normal ultrasound, treatment may be withheld without referring to angiography. |
| Perrier 2003 | Switzerland; tertiary care center in Geneva | Decision analytic model (decision tree);cost utility analysis | Third-party payer perspective | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 1996 | Hypothetical patients with suspected pulmonary embolism;10%, 37%, 69% for low, intermediate, and high clinical probability groups, respectively | The following strategies were compared: (1) V/Q scan ± angiography; (2) CT; (3) ultrasound ± CT; (4) d-dimer ± ultrasound ± CT; (5) d-dimer ± ultrasound ± CT ± angiography; (6) d-dimer ± ultrasound ± V/Q scan; (7) d-dimer ± ultrasound ± V/Q scan ± angiography; and (8) d-dimer ± ultrasound ± V/Q scan ± CT | For low clinical probability of pulmonary embolism patients, all strategies were reasonably effective, considering that the 3-mo survival remained within a range of 0.5% mortality compared with the reference strategy (V/Q scan ± angiography, $1728). The cheapest strategy was d-dimer ± ultrasound ± V/Q scan ($845), followed by d-dimer ± ultrasound ± CT ($1230). When clinical probability of pulmonary embolism was intermediate, the most cost-effective strategy was d-dimer ± ultrasound ± V/Q scan ± CT, in which a nondiagnostic V/Q scan is followed by helical CT ($2674). That strategy allowed us to forego pulmonary angiography in all patients. d-dimer ± ultrasound ± V/Q scan ± angiography was also cost saving compared with the reference strategy ($2832 vs $3164, respectively) and required an angiogram in 29% of patients. In patients with a high clinical probability of pulmonary embolism, d-dimer ± ultrasound ± V/Q scan ± CT remained the cheapest strategy ($4308) but was of marginal effectiveness (difference because of a higher proportion of patients treated unnecessarily, in 3-mo survival with the reference strategy, 0.47%). |
| Righini 2007 | Switzerland; emergency department | Decision analytic model (decision tree);cost utility analysis | Payer | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 2006 | 1721 consecutive patients with suspected pulmonary embolism; consecutive patients (unselected patients, prevalence unknown) | Four strategies were compared: (1) clinical probability ± d-dimer ± compression ultrasound ± helical CT; (2) clinical probability ± d-dimer ± helical CT; (3) clinical probability ± compression ultrasound ± helical CT; and (4) helical CT alone | All strategies were equally safe. Whatever the diagnostic strategy and whatever the age, the effectiveness remained very high, with variations in the 3-mo survival never exceeding 0.5% compared with the most effective strategy. Diagnostic strategies using d-dimer are less expensive. d-dimer measurement was highly cost-saving under the age of 80 y. |
| Van Beek 1996 | Netherlands; a secondary and tertiary referral center (both inpatient and outpatient) | Decision analytic model; cost-effectiveness analysis | Not reported (only direct costs were considered) | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | ECU, currency year not specified | 203 consecutive patients with suspected pulmonary embolism; consecutive patients (unselected patients, prevalence unknown) | The strategies compared include: (1) V/Q scan with ultrasound, if scan shows non-high probability and angiography, if ultrasound is normal; treatment if scan shows high probability, if ultrasound is abnormal, or if angiography shows pulmonary embolism; (2) d-dimer followed by strategy 1 if d-dimer elevated; (3) V/Q scan with d-dimer if scan shows non-high probability, ultrasound if d-dimer elevated and angiography if ultrasound is normal; treatment as strategy 1; (4) V/Q scan with angiography if scan shows non-high probability; treatment if scan shows high probability or if angiogram shows pulmonary embolism; (5) d-dimer followed by strategy 4 if d-dimer elevated; and (6) V/Q scan with d-dimer if scan shows non-high probability and angiography if d-dimer elevated; treatment as strategy 4 | Addition of the d-dimer assay to the diagnostic strategies does not result in any significant change in the mortality rates, whereas morbidity decreases to a slightly lower level. Addition of the d-dimer assay leads to an approximate 10% cost reduction in addition to a 25%-28% reduction in the number of patients requiring pulmonary angiography. |
| Van Erkel 1996 | Netherlands; a secondary and tertiary referral center | Decision analytic model (decision tree);cost-effectiveness analysis | Hospital | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism; 24% | Conventional angiographic strategies:(1) V/Q scanning, ultrasound, and conventional angiography; (2) ultrasound and conventional angiography; (3) V/Q scanning and conventional angiography; and (4) V/Q scanning, US, d-dimer assay, and conventional angiography. Spiral CT angiographic strategies:(5) spinal CT angiography; (6) ultrasound and spiral CT angiography; (7) perfusion scanning and spinal CT angiography; (8) perfusion scanning, US, and spiral CT angiography; (9) ultrasound, perfusion scanning, and spiral CT angiography; (10) V/Q scanning, ultrasound, and spiral CT angiography; (11) ultrasound, d-dimer assay, and spinal CT angiography; and (12) d-dimer assay and spiral CT angiography. Reference strategies:(13) no therapy; (14) therapy in all patients; and (15) ideal. | With the mortality or cost per life saved as the primary outcome parameter, the best strategies all included use of spiral CT angiography. Use of ultrasound before spiral CT angiography reduced the mortality but increased the cost per life saved ($20 562 per life saved vs $19 564 per life saved for spiral CT angiography only). The d-dimer test before spiral CT angiography increased the mortality but improved the marginal cost-effectiveness ($16 493 per life saved vs $19 564 per life saved for spiral CT angiography only). |
| Van Erkel 1998 | Netherlands; a secondary and tertiary referral center | Decision analytic model (decision tree);cost-effectiveness analysis | Hospital | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with suspected pulmonary embolism;24% | CT strategies:(1) CT; (2) ultrasound and CT; (3) perfusion scan and CT; (4) perfusion scan, ultrasound, and CT; (5) ultrasound, perfusion scan, and CT; and (6) V/Q scan, ultrasound, and CT. PA strategies: (7) ultrasound and pulmonary angiography; and (8) V/Q scan, ultrasound, and pulmonary angiography. d-dimer/CT strategies: (9) d-dimer and CT; (10) d-dimer, ultrasound, and CT; (11) d-dimer, perfusion scan, and CT; (12) d-dimer, perfusion scan, ultrasound, and CT; (13) d-dimer, ultrasound, perfusion scan, and CT; (14) d-dimer, V/Q scan, ultrasound, and CT, d-dimer/pulmonary angiography strategies; (15) d-dimer, ultrasound, and pulmonary angiography; and (16) d-dimer, V/Q scan, ultrasound, and pulmonary angiography. Reference strategies:(17) no therapy; and (18) all therapy. | Strategies using helical CT have lower costs and higher survival than strategies that use pulmonary angiography. With a willing to pay threshold of $500 000 for each additional life saved, the most cost-effective strategy under baseline conditions is ultrasound followed by helical CT. Using this strategy, the average patient survival is 99.39% at an average cost of $1125 per patient, leading to an incremental cost-effectiveness of $116 000 per extra life saved when compared with the best strategy previously recommended (the same algorithm but preceded by the d-dimer test). |
| Van Erkel 1999 | Netherlands; European and United States hospitals | Decision analytic model (decision tree);cost-effectiveness analysis | Not reported (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | ECU in 1997 | Hypothetical patients with suspected pulmonary embolism;24%. | CT strategies:(1) CT; (2) ultrasound, CT; (3) perfusion scan, CT; (4) perfusion scan, Ultrasound, CT; (5) ultrasound, perfusion scan, CT; (6) V/Q scan, ultrasound, CT; (7) d-dimer and CT; (8) d-dimer, ultrasound, CT;( 9) d-dimer, perfusion scan, CT; (10) d-dimer, perfusion scan, ultrasound, CT; (11) d-dimer, ultrasound, perfusion scan, CT; and 12) d-dimer, V/Q scan, ultrasound, CT. PA strategies:(13) ultrasound, pulmonary angiography; (14) V/Q scan, ultrasound, pulmonary angiography; (15) d-dimer, ultrasound, pulmonary angiography; and 16) d-dimer, V/Q scan, ultrasound, pulmonary angiography. Reference strategies:(17) no therapy; and (18) all therapy. | The most cost-effective strategy was ultrasound followed by helical CT. |
| V/Q scan or CTPA | ||||||||
| Batalles 2009 | Argentina; inpatient | Decision analytic model (decision tree);cost-effectiveness analysis | Third-party payer perspective | A short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2008 | Hypothetical patient who was hospitalized for another diagnosis other than PTE presented with an episode of sudden dyspnea;28.4%. | The strategies compared included: (1) V/Q lung scan; (2) spiral CT; (3) angiography by MDCT; (4) MRI; and (5) conventional arteriography. | The most cost-effective diagnostic test was angiography by MDCT. Compared with V/Q scan, the cost per additional diagnosis of pulmonary embolism was €127.2 for spiral CT. Angiography by MDCT cost €2168.4 for each additional PE diagnosis compared with spiral CT. MRI and conventional arteriography were dominated by angiography by MDCT. |
| Doyle 2004 | USA; not specified | Decision analytic model (decision tree);cost-effectiveness analysis | Third-party payer perspective | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | 100 hypothetical pregnant women or women in the puerperium with clinical suspicion for PE;5%. | Diagnostic test for PE in pregnancy included: (1) compression ultrasound followed by anticoagulation (if there is a positive result) or secondary tests, V/Q scans or spiral CT (if there is a negative result); (2) V/Q scans as a primary test followed by anticoagulation; and (3) computed tomography followed by anticoagulation (if there is a positive result). | The use of spiral CT as the primary modality for the diagnosis of a suspected PE was the most cost-effective strategy at $17 208 per life saved vs the compression ultrasound strategy ($24 004 per life saved) and the V/Q scan strategy ($35 906 per life saved). If V/Q scanning or compression ultrasound scanning is used as the primary diagnostic modality, spiral CT is the most cost-effective secondary test; more cost-effective than V/Q scans or pulmonary angiography. |
| Henschke 1997 | USA; not specified | Not specified (likely decision analytic model);cost-benefit analysis | Patient | 6 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients suspected with pulmonary embolism; unselected. | The strategies compared included: (1) V/Q scan; (2) pulmonary arteriography; (3) MR angiography; and (4) CT angiography. | When the test charges are used, when the mortality is $1 and the morbidity is $10K, the best test is V/Q scan for prevalence rates below 10%. As mortality costs increase above $1, V/Q scan becomes the best algorithm for all prevalence values. When the mortality cost is $100K, V/Q is just slightly better than CT angiography or MR angiography. V/Q scan remains the best algorithm as the mortality costs increases. |
| Hull 1996 | Canada; Midwest urban hospital affiliated with a university medical school | Decision analysis; cost-effectiveness analysis | Third-party payer perspective | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD), Can$ in 1992 | 662 patients with suspected acute pulmonary embolism; consecutive patients (unselected patients, prevalence unknown). | The strategies compared included: (1) V/Q lung scans and pulmonary angiography; (2) V/Q lung scans, single noninvasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography; and (3) V/Q lung scans, serial noninvasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography. | For strategy 1, the charges in the United States for each patient who requires treatment would be $14 421, and the charges incurred per patient correctly withheld from treatment would be $5978. For strategy 2, the charges in the United States for each patient who requires treatment would be $14 047, and the charges incurred per patient correctly withheld from treatment would be $5865 if the noninvasive leg test was impedance plethysmography; and $14 407 and $6016 respectively, if the noninvasive leg test was Doppler ultrasound with B-mode imaging. For strategy 3, the charges in the United States for each patient who requires treatment would be $12 639, and the charges incurred per patient correctly withheld from treatment would be $4333 if the noninvasive leg test was impedance plethysmography; and $13 842 and $4745 respectively, if the noninvasive leg test was Doppler ultrasound with B-mode imaging. |
| Hull 2001 | Canada; Midwest urban hospital affiliated with a university medical school | Decision analysis; cost-effectiveness analysis | Third-party payer perspective | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | Can$ in 1999 | 662 patients with suspected acute pulmonary embolism; consecutive patients (unselected patients, prevalence unknown). | The strategies compared included: (1) V/Q lung scans and pulmonary angiography; (2) V/Q lung scans, single noninvasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography; and (3) V/Q lung scans, serial non-invasive leg test (impedance plethysmography or Doppler ultrasound with B-mode imaging), and pulmonary angiography. | For strategy 1, the charges for each patient who requires treatment would be $10 761, and the charges incurred per patient correctly withheld from treatment would be $4461. For strategy 2, the charges for each patient who requires treatment would be $10 364, and the charges incurred per patient correctly withheld from treatment would be $4328. For strategy 3, the charges for each patient who requires treatment would be $8915, and the charges incurred per patient correctly withheld from treatment would be $3056. |
| Larcos 2000 | Australia; setting not specified | Decision analytic model (decision tree);cost-effectiveness analysis | Not reported (only direct costs were considered) | Lifetime horizon; life-years gained discounted: 3% | A$ in 1996/1997 | Hypothetical patients with suspected acute pulmonary embolism;34%. | The strategies compared included: (1) V/Q scan + ultrasound, pulmonary angiography; (2) CT scan alone; and (3) CT scan + ultrasound, pulmonary angiography. | The V/Q scan strategy was more effective (20.1 lives saved for every 1000 persons screened) and more costly (additional cost of A$315 per patient) compared with CT. The cost per life saved was A$940. If CT replaced V/Q scan in the screening, more lives could be saved (2.6 additional lives saved for every 1000 persons screened). Replacing V/Q scan with CT was also more costly (additional cost of A$979 per patient) compared with CT. The cost per life saved was A$23 905. |
| Muangman 2012 | Thailand; setting not specified | Prospective cohort; cost-effectiveness analysis | Not reported (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | ฿ currency year not specified | 100 cases with moderate to high probability for pulmonary embolism according to Wells criteria; moderate to high probability of pulmonary embolism. | Combined CTPA and indirect CTV was compared with strategy with sequential CTPA followed by direct CTV for negative PE cases. | The study found that 70 909 baht more per case for the combined CTPA and indirect CTV was needed for early detection of DVT (combined CTPA and indirect CTV: ฿3 744 000; sequential CTPA followed by direct CTV for negative PE cases: ฿2 964 000). |
| Oudkerk 1993 | Netherlands; inpatient | Decision analytic model; cost-effectiveness analysis | Unclear | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients with clinically suspected pulmonary embolism;30%. | The strategies compared included: (1) no treatment; (2) no diagnostic test; treatment of all patients; (3) perfusion scan and treatment if scan is abnormal; (4) perfusion scan, followed with angiography if scan is abnormal, treatment if pulmonary embolism is shown; (5) V/Q scan, treatment only If scan shows high probability; (6) V/Q scan, followed with angiography if scan shows non-high probability, treatment if scan shows high probability or if angiography shows pulmonary embolism; (7) angiography in all patients, treatment if pulmonary embolism is shown; (8) ultrasound in all patients, followed with angiography if ultrasound is normal, treatment if ultrasound is abnormal or if angiography shows pulmonary embolism; (9) V/Q scan, followed with ultrasound if scan shows non high probability, treatment if scan shows high probability or if ultrasound is abnormal; and (10) V/Q scan, followed with ultrasound if scan shows non high probability and angiography if ultrasound is normal, treatment if scan shows high probability, if ultrasound is abnormal, or if angiography shows pulmonary embolism. | The analysis identified 3 categories of strategies. The first category included treatment of all patients (or of those with an abnormal perfusion scan). These strategies had the lowest mortality and morbidity rates but the highest costs because of inappropriate treatment of 55% to 70% of patients. The second category included pulmonary angiography strategies with or without prior V/Q lung scintigraphy and ultrasound of the legs had comparable low mortality and morbidity rates, lower rate of inappropriate treatment (fewer than 5% of patients). But it saved cost by about 40% compared with the first category. The third category used V/Q scintigraphy with or without ultrasound, and this category led to unacceptably high mortality rates. |
| Paterson 2001 | Canada; inpatient and outpatient | Decision analytic model (decision tree);cost-effectiveness analysis | Third-party payer perspective | 3 mo; no discount (time horizon ≤ 1 y) | Can$ in 1996 | Simulated cohort of 1000 patients with suspected acute pulmonary embolism, with a prevalence of 28.4% | The following strategies were compared: (1) spiral CT followed by ultrasound; (2) spiral CT followed by ultrasound and then angiography; (3) V/Q scan followed by ultrasound then angiography; (4) V/Q scan followed by ultrasound and then spiral CT; (5) spiral CT followed by angiography; (6) spiral CT alone; and (7) V/Q scan followed by spiral CT. | Four of the strategies yielded poorer survival at higher cost (strategies 2, 5, 6, and 7). The 3 remaining strategies were as follows: strategy 3, V/Q ± leg ultrasound ± pulmonary angiography (the “traditional” algorithm), with an expected survival of 953.7 per 1000 patients and a cost of $1416 per patient; strategy 4, V/Q scan followed by leg ultrasound and then spiral CT, with an expected survival of 953.4 per 1000 patients and a cost of $1391 per patient; strategy 1, spiral CT followed by leg ultrasound, with an expected survival of 958.2 per 1000 patients and a cost of $1751 per patient. Strategy 3 was then excluded by extended dominance. The cost per additional life saved was $70 833 for strategy 1 (spiral CT followed by leg ultrasound) relative to strategy 4 (V/Q scan followed by leg ultrasound then spiral CT). |
| Toney 2017 | USA; emergency department | Decision analytic model; cost-effectiveness analysis | Payer | 30 d; no discount (time horizon ≤ 1 y) | $ (USD) in 2016 | Hypothetical cohort of 1000 patients with suspected acute pulmonary embolism presenting to an emergency department;22.7%. | The strategies compared included: (1) single-photon emission CT; (2) single-photon emission CT with CT; (3) nuclear medicine; and (4) CT pulmonary angiography. | Total costs for 1000 patients were $3 638 078, $3 203 039, $5 768 844, and $3 824 694 for single-photon emission CT, single-photon emission CT with CT, nuclear medicine, and CT pulmonary angiography, respectively. Switching to single-photon emission CT with CT strategy yielding per-patient-per-month cost savings of $51.80 (vs CT pulmonary angiography), $213.80 (vs nuclear medicine), and $36.30 (vs single-photon emission CT). Total lives lost per 1000 patients was 28.90, 28.82, 31.21, and 34.34 for single-photon emission CT, single-photon emission CT with CT, nuclear medicine, and CT pulmonary angiography, respectively. |
| Ultrasound | ||||||||
| Beecham 1993 | USA; setting not specified | Retrospective medical data review; cost comparison | Not reported (only direct costs were considered) | Not reported, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD) in 1993 | 223 consecutive patients suspected of pulmonary embolism; consecutive patients (unselected patients, prevalence unknown). | Pulmonary arteriography was compared with compression sonography plus pulmonary arteriography. | If all 145 patients whose lung scans were nondiagnostic had sonography and only those with normal sonograms had pulmonary arteriography, the professional and hospital charges would be $359 552. If all 145 had pulmonary arteriography without sonography, the charges would be $395 031. This study demonstrated that if V/Q lung scans indicated a low or an indeterminate probability of pulmonary embolism, only those patients with normal sonographic findings would need further study. |
| Ward 2011 | USA; emergency department | Decision analytic model (decision tree and Markov model);cost utility analysis | Societal | 6 mo;3% for effectiveness | $ (USD) in 2009 | Hypothetical 59 y old, hemodynamically stable female who presents with new-onset symptoms of pulmonary embolism;37.5%. | Selected CT (if ultrasound negative) was compared with universal CT strategy. | A selective CT strategy using compression US is cost-effective for patients with a high pretest probability of pulmonary embolism. The cost of universal CT strategy was $9051.94, whereas the cost was $7594.24 for a selective CT strategy. The selective CT strategy led to 0.0213 QALY gain compared with a universal CT strategy. |
| Other | ||||||||
| Goodacre 2018 | UK; UK National Health Service | Decision analytic model (decision tree);cost utility analysis | UK National Health Service and personal social service perspectives | Lifetime horizon;3.5% for both costs and benefits | £ in 2015/16 | Hypothetical pregnant or postpartum (up to 6 wk after birth) women who presented with a suspected pulmonary embolism at a UK hospital;6.5%. | The strategies compared included: (1) scanning all pregnant women with suspected pulmonary embolism (current recommended care); (2) applying the 3 expert-derived clinical consensus decision rules (primary, sensitive and specific); (3) applying a permissive interpretation of Wells’ decision rule (Wells’ permissive); (4) applying a strict interpretation of Wells’ decision rule (Wells’ strict); (5) applying the pulmonary embolism rule-out criteria decision rule; (6) applying the simplified Geneva decision rule; (7) scanning no women, but treating all; and (8) no scanning no treatment. | No scan, treat none, Wells’ score (strict), Delphi specificity score, Geneva score, Wells’ score (permissive), Delphi primary score, PERC score, no scan, treat all, Delphi sensitivity score all dominated by scan all. |
Abbreviations: CTV, computed tomography venography; ICER, incremental cost-effectiveness ratio; MRI, magnetic resonance imaging; MDCT, multidetector computed tomography; PERC, pulmonary embolism rule-out criteria; QALY, quality-adjusted life-years.
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