Economic evaluations of diagnostic and screening strategies for deep vein thrombosis
| Study . | Country/setting . | Study design/analytic technique . | Perspective . | Time horizon/discount . | Currency/y . | Population/pretest probability (prevalence) . | Intervention and comparison . | Results . |
|---|---|---|---|---|---|---|---|---|
| d-dimer | ||||||||
| Bogavac-Stanojevic 2013 | Serbia; vascular ambulance at Department of Clinic for Vascular surgery, Clinical Centre of Serbia | Prospective cohort; cost-effectiveness analysis | The clinical laboratory setting perspective | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2011 | 192 (95 male and 97 female) prospectively identified outpatients with clinically suspected acute DVT; unselected, prevalence unknown | Three D-dimer assays were compared: (1) Innovance d-dimer; (2) Vildas d-dimer; (3) Hemosil d-dimer In the first decision analytic model, tests were applied for all patients; in the second decision analytic model, tests were applied only to patients with low and moderate pretest probability. | The diagnostic alternative employing Vidas d-dimer Exclusion II assay was cost-effective compared with the alternative employing Hemosil d-dimer HS assay. Compared with the Innovance d-dimer assay, the ICER (incremental cost per additional DVT positive patient selected for compression ultrasound) was estimated to be €0.187 for Vidas d-dimer assay and vs €0.998 for Hemosil d-dimer assay in patients selected for compression ultrasound, if there was no pretest probability assessment. When pretest probability was considered, the incremental cost per additional DVT positive patient was estimated to be €0.450 for Innovance d-dimer assay and €0.753 for Hemosil d-dimer assay. |
| D’Angelo 1996 | Italy; inpatient and outpatient | Prospective cohort; cost-effectiveness analysis | NR (only direct costs of tests were considered) | 6 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | 103 patients with suspected DVT; consecutive patients (including low, moderate, and high clinical probability) | Ultrasound alone was compared with d-dimer and compression ultrasound | In patients with a first episode of suspected DVT (n = 66), the cost saving per DVT diagnosed for d-dimer and compression ultrasound vs ultrasound alone was estimated to be 55% in 15 patients with low clinical pretest probability, and 38% in 24 patients with moderate clinical pretest probability, and 5% in 27 patients with high clinical probability. In 37 patients with suspected DVT recurrence, the cost saving per DVT diagnosed was estimated to be 77%. |
| Del Rio Sola 1999 | Spain; emergency department | Prospective cohort; cost-effectiveness analysis | NR | 3 mo; No discount (time horizon ≤ 1 y) | NR | 175 symptomatic patients with suspected DVT; consecutive patients (unselected patients, prevalence unknown) | d-dimer test was compared with no d-dimer test | The diagnosis carried out through a combination of clinical suspicion and high d-dimer levels permits a significant saving of economic resources, insofar as a considerable number of patients, 48% are excluded from further tests. |
| Dryjski 2001 | USA; emergency department | Prospective cohort; cost comparison | NR (only direct costs of tests were considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD) in 2000 and 2001 | 114 patients with suspected DVT; Consecutive patients (unselected patients, prevalence unknown) | The strategies compared were: (1) global pretest probability, direct venous duplex imaging for high-risk patients, and d-dimer for low-risk and moderate-risk patients, with selective venous duplex imaging for low- and moderate-risk patients having positive d-dimer results; (2) direct venous duplex imaging for all. | This study proposed a screening strategy: for high-risk patients, use direct venous duplex imaging (no d-dimer); for low-risk or moderate-risk patients, obtain d-dimer, and if it is positive, use venous duplex imaging, and if it is negative, no further action is required. The estimated average cost was $170.50 for this strategy, and $202.00 for the strategy using direct venous duplex imaging for all. |
| Goodacre 2006 | 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 2003/04 | Hypothetical patients suspected to have DVT; consecutive patients (unselected patients, prevalence unknown) | Thirty-one algorithms including Wells score, d-dimer, ultrasound were compared: (1) algorithm 1, a “no testing, no treatment” alternative; (2) algorithms 2, 3, 4, 5, 6, 7, 8, 14, 17, and 18 require all patients to have ultrasound; algorithms 9, 10, 11, 12, 15, 16, 20, 22, 23, 24, 27, and 28 discharge on the basis of a combination of Wells score and d-dimer; (3) algorithms 19, 26, 29, and 30 discharge on the basis of negative plethysmography and d-dimer; (4) algorithm 21 discharges on the basis of a low Wells score alone; (5) algorithms 13 and 25 discharge on the basis of negative d-dimer alone; (6) algorithm 31 discharges on the basis of a combination of Wells score and plethysmography. | Algorithm 20 had the greatest net benefit. Two algorithms (9 and 10) also had a consistently high net benefit regardless of the threshold used. All of these algorithms used d-dimer and Wells score as an initial screening tool, before progressing to ultrasound with repeat. At the thresholds for willingness to pay recommended by the National Institute for Clinical and Healthcare Excellence (£20 000-£30 000 per QALY), the optimal strategy was to discharge patients with a low or intermediate Wells score and negative d-dimer, limiting ultrasound to those with a high score or positive d-dimer. Strategies using radiological testing for all patients were only cost-effective at £40 000 per QALY or more. |
| Heijboer 1992 | Netherlands; outpatients with clinically suspected DVT | Cross-sectional study; cost-effectiveness analysis | NR (only direct costs of tests were considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | ECU, currency year not specified | 474 outpatients with a clinically suspected first episode of acute DVT of the leg; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) combination of d-dimer test and impedance plethysmography; (2) combination of d-dimer test and real-them ultrasound; (3) serial impedance plethysmography; (4) serial ultrasound. | For the cost per diagnosis, combination strategy of d-dimer test and impedance plethysmography had comparable cost (ECU 435) with serial impedance plethysmography (ECU 415). Similarly, the combination d-dimer test and real-time ultrasound had similar cost per diagnosis (ECU 695) with serial ultrasound (ECU 729). |
| Hendriksen 2015 | Netherlands; primary care | Decision analytic model (Markov model); cost utility analysis/ cost minimization analysis | NR (only direct costs were considered) | 10 y; 4% for cost and 1.5% for outcomes | € in 2010 | Hypothetical patients suspected to have DVT; 13.57% | The following strategies were compared: (1) triage POC test; (2) cardiac POC test; (3) Mycocard POC test; (4) simplify POC test; (5) laboratory strategy (hospital-based laboratory testing); (6) hospital strategy, referral to hospital for further testing for all patients. | The laboratory strategy led to 6.986 QALYs at the cost of €8354 per patient. This study found all point of care d-dimer strategies led to similar health outcomes as the laboratory strategy, but the point of care d-dimer tests were cost-saving (Simplify d-dimer: €-155.37; Nycocard d-dimer: €-56.43; Cardiac d-dimer: €-83.20; Triage d-dimer: €-16.87; and hospital strategy: €113.59). |
| Michiels 1999 | Netherlands; outpatient | Decision analytic model; cost comparison | NR (indirect cost considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | fl., currency year not specified | Hypothetical patients suspected to have DVT; consecutive patients (unselected patients, prevalence unknown) | Consensus strategy of serial compression ultrasound was compared with d-dimer test. | The total diagnosis cost per 15 million inhabitants in the Netherlands was estimated to be fl. 13.4 million for the consensus strategy of serial compression ultrasound, and fl. 8.7 million for the d-dimer before compression ultrasound. This led to cost-saving of fl. 4.7 million annually when only direct costs were considered, and fl. 15 to 20 million when indirect costs were also considered. |
| Norlin 2010 | Sweden; emergency department | Decision analytic model; cost-effectiveness analysis | Societal perspective (in a Swedish setting) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2008 | 357 suspected cases of DVT at emergency departments; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) compression ultrasound and/or contrast venography for all patients; (2) Wells score with d-dimer (to rule out low probability patients); (3) d-dimer with Wells score (to rule out low probability patients). | The total cost per patient was estimated to be €581 for the traditional strategy of compression ultrasound and/or contrast venography was €406 for the pretest probability and d-dimer strategy, and €421 for the strategy with reversed order combination (d-dimer then pretest probability). |
| Novielli 2013 | UK; setting not specified | Decision analytic model (decision tree and Markov model); cost-effectiveness analysis | Unclear | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | £, currency year not specified | Hypothetical patients suspected to have DVT; unselected, prevalence unknown | Three strategies were compared: (1) combination strategies of Wells score and d-dimer; (2) no test, treat all; (3) no test, treat none. | Assuming the diagnostic performance of the 2 tests to be independent, the strategy “Wells score moderate/high risk treated for DVT and Wells score low risk tested further with d-dimer” was identified as the most cost-effective at the £20 000 willingness-to-pay threshold (probability cost-effective 0.8). When performance dependence is modeled, the most cost-effective strategies were “d-dimer alone” and “Wells score low/moderate risk discharged and Wells score high risk further tested with d-dimer” (probability cost-effective 0.4). |
| Perone 2001 | Switzerland; inpatient and outpatient | Decision analytic model (decision tree); cost utility analysis | NR (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 1996 | Hypothetical patients suspected to have DVT; 24% | The following strategies were compared: (1) no treatment; (2) serial ultrasound; (3) serial ultrasound with d-dimer; (4) risk-based serial ultrasound; (5) d-dimer with risk-based single ultrasound. | Compared with no treatment, the 4 strategies led to similar effectiveness, saving 4.6 to 4.8 lives per 1000 patients. But the costs of 4 strategies differed. The most expensive strategy was serial ultrasound strategy ($1482 per patient), then serial ultrasound with d-dimer ($1425 per patient), followed by risk-based serial ultrasound ($1402), and d-dimer with risk-based single ultrasound ($1200). The ICER, indicated by incremental cost per additional QALY, was estimated to be $10 716, $10 281, $10 090, and $8897 per QALY for serial ultrasound, serial ultrasound with d-dimer, risk-based serial ultrasound, and d-dimer with risk-based single ultrasound. |
| Reardon 2019 | Canada; emergency department | Retrospective cohort; cost comparison | NR (only direct costs were considered) | 30 d; no discount (time horizon ≤ 1 y) | Can$, currency year not specified | 972 patients presenting to emergency department with suspected DVT; consecutive patients (unselected patients, prevalence unknown) | Three strategies were compared: (1) conventional cutoff value 500 ng/mL; (2) age-adjusted cutoff (age*10); (3) absolute cutoff value 1000 ng/mL. | The conventional cutoff of <500 ng/mL demonstrated a sensitivity of 100% (95% confidence interval [CI], 94.3-100) and a specificity of 35.6% (95% CI, 32.5-38.8). Both age-adjusted cutoff strategy and absolute cutoff value of 1000 ng/mL had maintained the high sensitivity while improved specificity (age-adjusted cutoff: 49.9% [95% CI, 46.7-53.3]; absolute cutoff value 1000 ng/mL, 66.3% [95% CI, 63.2-69.4]). Both the 1000 ng/mL cutoff and the age-adjusted cutoffs were cost-saving compared with the conventional approach (cost saving per patient for age-adjusted cutoff: Can$79; Absolute cutoff value 1000 ng/mL: Can$172). |
| Ultrasound | ||||||||
| Bendayan 1991 | France; hospitalized and ambulatory patients | Prospective cohort; cost-effectiveness analysis | NR (only direct costs were considered) | 6 mo; no discount (time horizon ≤ 1 y) | FF; year not specified | 511 consecutive patients suspected of DVT of the lower limbs; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) clinical; (2) echography followed by plethysmography; (3) echography followed by plethysmography and venography; (4) contrast venography. | The total costs were 8276110 FF, 2127362 FF, 2286793 FF, and 2893404 FF, and 2893404 FF for clinical strategy, echography followed by plethysmography strategy, echography followed by plethysmography and venography strategy, and contrast venography. Health outcomes were not compared. |
| Hillner 1992 | USA; ambulatory patients | Decision analytic model (decision tree and Markov model); cost-effectiveness analysis | Unclear | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 1990 | Hypothetical patients suspected to have lower extremity DVT; 10% for calf DVT and 30% for thigh DVT | In total, 24 strategies were compared: treat none or treat all, venography first, 1 noninvasive test, 2 noninvasive tests, or 3 noninvasive tests. | This analysis revealed that the optimal approach was to perform real-time ultrasound followed by anticoagulation therapy if DVT is found. This approach was both effective and cost saving compared with no testing or treatment. Serial follow-up studies of patients whose initial study suggested no DVT saved additional lives, but at a cost of $390 000 per each additional life saved for patients with one follow-up study and $3.5 million per each additional life saved for patients with a second follow-up study. |
| Hull 1995 | Canada; regional thromboembolism program | Prospective cohort; cost minimization analysis | NR (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), Can$ in 1992 | 516 patients referred to a regional thromboembolism program with a first episode of clinically suspected DVT; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) serial Doppler ultrasound; (2) serial impedance plethysmography; (3) combined Doppler ultrasound and serial impedance plethysmography. | Outpatient diagnosis using noninvasive testing was the most cost effective. Serial Doppler ultrasound is more costly (Can $618 265, US$1 326 180) than serial impedance plethysmography (Can$527 165, US$1 052 880), and combined Doppler ultrasound and serial impedance plethysmography (Can$551 065, US$1 124 580). |
| Kim 2000 | USA; inpatient | Decision analytic model (Markov model); cost utility analysis | Medicare charges | Lifetime horizon; 3% for both cost and effectiveness | $ (USD) in 1996 | Hypothetical 65-y-old male patients suspected to have DVT; 31.8% | Six initial strategies were considered: (1) unilateral examination of the common femoral and popliteal veins; (2) unilateral examination of the common femoral, popliteal, and femoral veins; (3) bilateral examination of the common femoral and popliteal veins; (4) bilateral examination of the common femoral, popliteal, and femoral veins; (5) complete unilateral examination of symptomatic leg (including calf veins); (6) complete bilateral examination of both legs Five follow-up strategies of popliteal vein within 5 d: 1) no initial treatment and no follow-up testing; 2) unilateral examination of the popliteal vein; 3) unilateral examination of the common femoral and popliteal veins; 4) unilateral examination of the common femoral, popliteal, and femoral veins; 5) bilateral limited examination of the common femoral and popliteal veins | For 65-y-old men with unilateral symptoms of DVT, the most effective strategy was bilateral examination of the common femoral and popliteal veins, anticoagulation therapy in patients with proximal DVT, and follow-up bilateral examination of the common femoral and popliteal veins in patients without an initial diagnosis of DVT. This strategy had an incremental cost-effectiveness ratio of $39 000 per quality-adjusted life year gained compared with strategy of unilateral common femoral, popliteal examination and no follow-up. |
| Samuel 2019 | USA; major academic tertiary care medical center | Quasi-experimental study; cost-effectiveness analysis | NR (only direct costs were considered) | 14 d; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | 157 adults underwent cranial or spinal surgical interventions; high-risk patients who present with brain injury and require surgical interventions | Routine ultrasound screening was compared with standard screening. | For diagnostic performance, detecting 1 DVT required 6 vs 27 ultrasound screening studies in the standard screening and the routine screening group, respectively. Total cost incurred per DVT diagnosis was lower for the standard screening approach ($13 664) versus the routine screening approach ($56 525). |
| Wilson 2005 | USA; inpatient stroke rehabilitation unit | Decision analytic model (decision tree); cost utility analysis | Societal | 4 y (life expectancy of those with ischemic stroke); no discount | $ (USD) in 2004 | Hypothetical patients with ischemic stroke at the time of admission to rehabilitation at risk of DVT; 12% | Two strategies were compared: (1) screening all patients with acute ischemic stroke for DVT by Doppler ultrasound; (2) clinical surveillance for signs of DVT and treatment after confirmation by Doppler ultrasound. | The expected health outcomes were 1.875 QALYs for ultrasound screening strategy and 1.872 QALYs for no screening strategy. The expected cost per patient was $330 for ultrasound screening strategy, compared with $162 for no screening. The ICER was estimated to be $67 200 per QALY gained. |
| Other | ||||||||
| Fuentes 2016 | Spain; hospital emergency room | Cross-sectional study; cost-effectiveness analysis | NR (only direct costs were considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2013 | 138 patients with symptoms of a first episode of DVT; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) current approach; (2) Oudega clinical probability algorithm; (3) Wells clinical probability algorithm. | Compared with current approach, the cost saving per patient was estimated to be €86.19 for Oudega clinical probability algorithm, and €97.40 for Wells clinical probability algorithm. |
| Hedderich 2019 | USA; emergency department | Decision analytic model (decision tree); cost utility analysis | US health care perspective | Lifetime horizon; 3% for both cost and effectiveness | $ (USD) in 2017 | Hypothetical patients admitted to the emergency department for possible CVT; low (1.6%) and high (50%) | The following strategies were compared: (1) NCCT; (2) NCCT plus CTV; (3) routine MRI; (4) routine MRI plus MRV. | Two strategies, NCCT and NCCT plus CTV were dominant over routine MRI and routine MRI plus MRV. NCCT plus CTV led to more QALYs (23.385 QALYs) compared with NCCT (23.374 QALYs), but also are more costly ($5210 for NCCT plus CTV versus $5057 for NCCT). Probabilistic sensitivity analysis found that CTV was the strategy with the highest percentage of cost-effective iterations if willingness-to-pay (WTP) thresholds were higher than $13 750/QALY. |
| Van Dam 2021 | Netherlands and Norway; emergency department | Decision analytic model; cost-effectiveness analysis | NR (only direct costs were considered) | 1 y; no discount (time horizon ≤ 1 y) | € in 2019 | Adult patients with suspected recurrent ipsilateral proximal DVT of the lower extremity on or off anticoagulant treatment; 43% (for recurrent DVT) | 13 diagnostic scenarios: (1) MRDTI only; (2) ultrasound (normal/abnormal) only; (3) ultrasound (positive/negative/inconclusive) only; (4) only ultrasound (normal/abnormal) in case of a likely clinical decision rule and/or abnormal D-dimer; (5) only ultrasound (positive/negative/inconclusive) in case of a likely clinical decision rule and/or abnormal D-dimer; (6) only MRDTI in case of an abnormal ultrasound; (7) only MRDTI in case of an inconclusive ultrasound; (8) only MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer; (9) only MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer and an abnormal ultrasound; (10) MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer and an inconclusive ultrasound; (11) Clinical decision rule and d-dimer; (12) treat all; (13) treat none | Total 1-y health care costs (€) per person and total mortality per 10 000 patients (1) MRDTI only: €1,271 and 18 deaths per 10 000 patients; (2) ultrasound (normal/abnormal) only: €1529 and 14 deaths per 10 000 patients; (3) ultrasound (positive/negative/inconclusive) only: €1378 and 15 deaths per 10 000 patients; (4) only ultrasound (normal/abnormal) in case of a likely clinical decision rule and/or abnormal D-dimer: €1365 and 16 deaths per 10 000 patients; (5) only ultrasound (positive/negative/inconclusive) in case of a likely clinical decision rule and/or abnormal D-dimer: €1278 and 17 deaths per 10 000 patients; (6) only MRDTI in case of an abnormal ultrasound: €1296 and 18 deaths per 10 000 patients; (7) only MRDTI in case of an inconclusive ultrasound: €1263 and 16 deaths per 10 000 patients; (8) only MRDTI in case of a likely clinical decision rule and/or abnormal D-Dimer: €1230 and 19 deaths per 10 000 patients; (9) only MRDTI in case of a likely clinical decision rule and/or abnormal D-Dimer and an abnormal ultrasound: €1260 and 19 deaths per 10 000 patients; (10) MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer and an inconclusive ultrasound: €1219 and 17 deaths per 10 000 patients; (11) clinical decision rule and d-Dimer: €1654 and 14 deaths per 10 000 patients; (11) treat all: €2004 and 10 deaths per 10 000 patients; (13) treat none: 1239 and 104 deaths per 10 000 patients. Strategies with MRDTI for suspected recurrent ipsilateral DVT decreased 1-y health care costs compared with strategies without MRDTI, with similar impact on mortality. |
| CTPA for both PE and DVT | ||||||||
| Henschke 1994 | USA; not specified | Not specified (likely decision analytic model); cost-effectiveness analysis | NR (only direct cost of tests was considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients suspected with pulmonary embolism and DVT; unselected, prevalence unknown | Five strategies were compared: (1) angiogram; (2) radionuclide venography; (3) contrast venography; (4) sonography with Doppler; (5) radionuclide V/Q scan. | Effective cost, the money spent per unit of diagnostic information, was defined as the ratio of the expected direct test cost to its diagnostic performance. The effective cost was lowest for Doppler sonography, estimated to be between $378 and $486, followed by radionuclide leg venography ($843). The effective cost was estimated to be between $1557 and $2001 for contrast venography and $2061 for angiography, whereas the effective cost for radionuclide with V/Q scan depends on the prevalence of pulmonary embolism and morbidity and mortality cost. |
| Study . | Country/setting . | Study design/analytic technique . | Perspective . | Time horizon/discount . | Currency/y . | Population/pretest probability (prevalence) . | Intervention and comparison . | Results . |
|---|---|---|---|---|---|---|---|---|
| d-dimer | ||||||||
| Bogavac-Stanojevic 2013 | Serbia; vascular ambulance at Department of Clinic for Vascular surgery, Clinical Centre of Serbia | Prospective cohort; cost-effectiveness analysis | The clinical laboratory setting perspective | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2011 | 192 (95 male and 97 female) prospectively identified outpatients with clinically suspected acute DVT; unselected, prevalence unknown | Three D-dimer assays were compared: (1) Innovance d-dimer; (2) Vildas d-dimer; (3) Hemosil d-dimer In the first decision analytic model, tests were applied for all patients; in the second decision analytic model, tests were applied only to patients with low and moderate pretest probability. | The diagnostic alternative employing Vidas d-dimer Exclusion II assay was cost-effective compared with the alternative employing Hemosil d-dimer HS assay. Compared with the Innovance d-dimer assay, the ICER (incremental cost per additional DVT positive patient selected for compression ultrasound) was estimated to be €0.187 for Vidas d-dimer assay and vs €0.998 for Hemosil d-dimer assay in patients selected for compression ultrasound, if there was no pretest probability assessment. When pretest probability was considered, the incremental cost per additional DVT positive patient was estimated to be €0.450 for Innovance d-dimer assay and €0.753 for Hemosil d-dimer assay. |
| D’Angelo 1996 | Italy; inpatient and outpatient | Prospective cohort; cost-effectiveness analysis | NR (only direct costs of tests were considered) | 6 mo; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | 103 patients with suspected DVT; consecutive patients (including low, moderate, and high clinical probability) | Ultrasound alone was compared with d-dimer and compression ultrasound | In patients with a first episode of suspected DVT (n = 66), the cost saving per DVT diagnosed for d-dimer and compression ultrasound vs ultrasound alone was estimated to be 55% in 15 patients with low clinical pretest probability, and 38% in 24 patients with moderate clinical pretest probability, and 5% in 27 patients with high clinical probability. In 37 patients with suspected DVT recurrence, the cost saving per DVT diagnosed was estimated to be 77%. |
| Del Rio Sola 1999 | Spain; emergency department | Prospective cohort; cost-effectiveness analysis | NR | 3 mo; No discount (time horizon ≤ 1 y) | NR | 175 symptomatic patients with suspected DVT; consecutive patients (unselected patients, prevalence unknown) | d-dimer test was compared with no d-dimer test | The diagnosis carried out through a combination of clinical suspicion and high d-dimer levels permits a significant saving of economic resources, insofar as a considerable number of patients, 48% are excluded from further tests. |
| Dryjski 2001 | USA; emergency department | Prospective cohort; cost comparison | NR (only direct costs of tests were considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD) in 2000 and 2001 | 114 patients with suspected DVT; Consecutive patients (unselected patients, prevalence unknown) | The strategies compared were: (1) global pretest probability, direct venous duplex imaging for high-risk patients, and d-dimer for low-risk and moderate-risk patients, with selective venous duplex imaging for low- and moderate-risk patients having positive d-dimer results; (2) direct venous duplex imaging for all. | This study proposed a screening strategy: for high-risk patients, use direct venous duplex imaging (no d-dimer); for low-risk or moderate-risk patients, obtain d-dimer, and if it is positive, use venous duplex imaging, and if it is negative, no further action is required. The estimated average cost was $170.50 for this strategy, and $202.00 for the strategy using direct venous duplex imaging for all. |
| Goodacre 2006 | 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 2003/04 | Hypothetical patients suspected to have DVT; consecutive patients (unselected patients, prevalence unknown) | Thirty-one algorithms including Wells score, d-dimer, ultrasound were compared: (1) algorithm 1, a “no testing, no treatment” alternative; (2) algorithms 2, 3, 4, 5, 6, 7, 8, 14, 17, and 18 require all patients to have ultrasound; algorithms 9, 10, 11, 12, 15, 16, 20, 22, 23, 24, 27, and 28 discharge on the basis of a combination of Wells score and d-dimer; (3) algorithms 19, 26, 29, and 30 discharge on the basis of negative plethysmography and d-dimer; (4) algorithm 21 discharges on the basis of a low Wells score alone; (5) algorithms 13 and 25 discharge on the basis of negative d-dimer alone; (6) algorithm 31 discharges on the basis of a combination of Wells score and plethysmography. | Algorithm 20 had the greatest net benefit. Two algorithms (9 and 10) also had a consistently high net benefit regardless of the threshold used. All of these algorithms used d-dimer and Wells score as an initial screening tool, before progressing to ultrasound with repeat. At the thresholds for willingness to pay recommended by the National Institute for Clinical and Healthcare Excellence (£20 000-£30 000 per QALY), the optimal strategy was to discharge patients with a low or intermediate Wells score and negative d-dimer, limiting ultrasound to those with a high score or positive d-dimer. Strategies using radiological testing for all patients were only cost-effective at £40 000 per QALY or more. |
| Heijboer 1992 | Netherlands; outpatients with clinically suspected DVT | Cross-sectional study; cost-effectiveness analysis | NR (only direct costs of tests were considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | ECU, currency year not specified | 474 outpatients with a clinically suspected first episode of acute DVT of the leg; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) combination of d-dimer test and impedance plethysmography; (2) combination of d-dimer test and real-them ultrasound; (3) serial impedance plethysmography; (4) serial ultrasound. | For the cost per diagnosis, combination strategy of d-dimer test and impedance plethysmography had comparable cost (ECU 435) with serial impedance plethysmography (ECU 415). Similarly, the combination d-dimer test and real-time ultrasound had similar cost per diagnosis (ECU 695) with serial ultrasound (ECU 729). |
| Hendriksen 2015 | Netherlands; primary care | Decision analytic model (Markov model); cost utility analysis/ cost minimization analysis | NR (only direct costs were considered) | 10 y; 4% for cost and 1.5% for outcomes | € in 2010 | Hypothetical patients suspected to have DVT; 13.57% | The following strategies were compared: (1) triage POC test; (2) cardiac POC test; (3) Mycocard POC test; (4) simplify POC test; (5) laboratory strategy (hospital-based laboratory testing); (6) hospital strategy, referral to hospital for further testing for all patients. | The laboratory strategy led to 6.986 QALYs at the cost of €8354 per patient. This study found all point of care d-dimer strategies led to similar health outcomes as the laboratory strategy, but the point of care d-dimer tests were cost-saving (Simplify d-dimer: €-155.37; Nycocard d-dimer: €-56.43; Cardiac d-dimer: €-83.20; Triage d-dimer: €-16.87; and hospital strategy: €113.59). |
| Michiels 1999 | Netherlands; outpatient | Decision analytic model; cost comparison | NR (indirect cost considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | fl., currency year not specified | Hypothetical patients suspected to have DVT; consecutive patients (unselected patients, prevalence unknown) | Consensus strategy of serial compression ultrasound was compared with d-dimer test. | The total diagnosis cost per 15 million inhabitants in the Netherlands was estimated to be fl. 13.4 million for the consensus strategy of serial compression ultrasound, and fl. 8.7 million for the d-dimer before compression ultrasound. This led to cost-saving of fl. 4.7 million annually when only direct costs were considered, and fl. 15 to 20 million when indirect costs were also considered. |
| Norlin 2010 | Sweden; emergency department | Decision analytic model; cost-effectiveness analysis | Societal perspective (in a Swedish setting) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2008 | 357 suspected cases of DVT at emergency departments; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) compression ultrasound and/or contrast venography for all patients; (2) Wells score with d-dimer (to rule out low probability patients); (3) d-dimer with Wells score (to rule out low probability patients). | The total cost per patient was estimated to be €581 for the traditional strategy of compression ultrasound and/or contrast venography was €406 for the pretest probability and d-dimer strategy, and €421 for the strategy with reversed order combination (d-dimer then pretest probability). |
| Novielli 2013 | UK; setting not specified | Decision analytic model (decision tree and Markov model); cost-effectiveness analysis | Unclear | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | £, currency year not specified | Hypothetical patients suspected to have DVT; unselected, prevalence unknown | Three strategies were compared: (1) combination strategies of Wells score and d-dimer; (2) no test, treat all; (3) no test, treat none. | Assuming the diagnostic performance of the 2 tests to be independent, the strategy “Wells score moderate/high risk treated for DVT and Wells score low risk tested further with d-dimer” was identified as the most cost-effective at the £20 000 willingness-to-pay threshold (probability cost-effective 0.8). When performance dependence is modeled, the most cost-effective strategies were “d-dimer alone” and “Wells score low/moderate risk discharged and Wells score high risk further tested with d-dimer” (probability cost-effective 0.4). |
| Perone 2001 | Switzerland; inpatient and outpatient | Decision analytic model (decision tree); cost utility analysis | NR (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 1996 | Hypothetical patients suspected to have DVT; 24% | The following strategies were compared: (1) no treatment; (2) serial ultrasound; (3) serial ultrasound with d-dimer; (4) risk-based serial ultrasound; (5) d-dimer with risk-based single ultrasound. | Compared with no treatment, the 4 strategies led to similar effectiveness, saving 4.6 to 4.8 lives per 1000 patients. But the costs of 4 strategies differed. The most expensive strategy was serial ultrasound strategy ($1482 per patient), then serial ultrasound with d-dimer ($1425 per patient), followed by risk-based serial ultrasound ($1402), and d-dimer with risk-based single ultrasound ($1200). The ICER, indicated by incremental cost per additional QALY, was estimated to be $10 716, $10 281, $10 090, and $8897 per QALY for serial ultrasound, serial ultrasound with d-dimer, risk-based serial ultrasound, and d-dimer with risk-based single ultrasound. |
| Reardon 2019 | Canada; emergency department | Retrospective cohort; cost comparison | NR (only direct costs were considered) | 30 d; no discount (time horizon ≤ 1 y) | Can$, currency year not specified | 972 patients presenting to emergency department with suspected DVT; consecutive patients (unselected patients, prevalence unknown) | Three strategies were compared: (1) conventional cutoff value 500 ng/mL; (2) age-adjusted cutoff (age*10); (3) absolute cutoff value 1000 ng/mL. | The conventional cutoff of <500 ng/mL demonstrated a sensitivity of 100% (95% confidence interval [CI], 94.3-100) and a specificity of 35.6% (95% CI, 32.5-38.8). Both age-adjusted cutoff strategy and absolute cutoff value of 1000 ng/mL had maintained the high sensitivity while improved specificity (age-adjusted cutoff: 49.9% [95% CI, 46.7-53.3]; absolute cutoff value 1000 ng/mL, 66.3% [95% CI, 63.2-69.4]). Both the 1000 ng/mL cutoff and the age-adjusted cutoffs were cost-saving compared with the conventional approach (cost saving per patient for age-adjusted cutoff: Can$79; Absolute cutoff value 1000 ng/mL: Can$172). |
| Ultrasound | ||||||||
| Bendayan 1991 | France; hospitalized and ambulatory patients | Prospective cohort; cost-effectiveness analysis | NR (only direct costs were considered) | 6 mo; no discount (time horizon ≤ 1 y) | FF; year not specified | 511 consecutive patients suspected of DVT of the lower limbs; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) clinical; (2) echography followed by plethysmography; (3) echography followed by plethysmography and venography; (4) contrast venography. | The total costs were 8276110 FF, 2127362 FF, 2286793 FF, and 2893404 FF, and 2893404 FF for clinical strategy, echography followed by plethysmography strategy, echography followed by plethysmography and venography strategy, and contrast venography. Health outcomes were not compared. |
| Hillner 1992 | USA; ambulatory patients | Decision analytic model (decision tree and Markov model); cost-effectiveness analysis | Unclear | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD) in 1990 | Hypothetical patients suspected to have lower extremity DVT; 10% for calf DVT and 30% for thigh DVT | In total, 24 strategies were compared: treat none or treat all, venography first, 1 noninvasive test, 2 noninvasive tests, or 3 noninvasive tests. | This analysis revealed that the optimal approach was to perform real-time ultrasound followed by anticoagulation therapy if DVT is found. This approach was both effective and cost saving compared with no testing or treatment. Serial follow-up studies of patients whose initial study suggested no DVT saved additional lives, but at a cost of $390 000 per each additional life saved for patients with one follow-up study and $3.5 million per each additional life saved for patients with a second follow-up study. |
| Hull 1995 | Canada; regional thromboembolism program | Prospective cohort; cost minimization analysis | NR (only direct costs were considered) | 3 mo; no discount (time horizon ≤ 1 y) | $ (USD), Can$ in 1992 | 516 patients referred to a regional thromboembolism program with a first episode of clinically suspected DVT; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) serial Doppler ultrasound; (2) serial impedance plethysmography; (3) combined Doppler ultrasound and serial impedance plethysmography. | Outpatient diagnosis using noninvasive testing was the most cost effective. Serial Doppler ultrasound is more costly (Can $618 265, US$1 326 180) than serial impedance plethysmography (Can$527 165, US$1 052 880), and combined Doppler ultrasound and serial impedance plethysmography (Can$551 065, US$1 124 580). |
| Kim 2000 | USA; inpatient | Decision analytic model (Markov model); cost utility analysis | Medicare charges | Lifetime horizon; 3% for both cost and effectiveness | $ (USD) in 1996 | Hypothetical 65-y-old male patients suspected to have DVT; 31.8% | Six initial strategies were considered: (1) unilateral examination of the common femoral and popliteal veins; (2) unilateral examination of the common femoral, popliteal, and femoral veins; (3) bilateral examination of the common femoral and popliteal veins; (4) bilateral examination of the common femoral, popliteal, and femoral veins; (5) complete unilateral examination of symptomatic leg (including calf veins); (6) complete bilateral examination of both legs Five follow-up strategies of popliteal vein within 5 d: 1) no initial treatment and no follow-up testing; 2) unilateral examination of the popliteal vein; 3) unilateral examination of the common femoral and popliteal veins; 4) unilateral examination of the common femoral, popliteal, and femoral veins; 5) bilateral limited examination of the common femoral and popliteal veins | For 65-y-old men with unilateral symptoms of DVT, the most effective strategy was bilateral examination of the common femoral and popliteal veins, anticoagulation therapy in patients with proximal DVT, and follow-up bilateral examination of the common femoral and popliteal veins in patients without an initial diagnosis of DVT. This strategy had an incremental cost-effectiveness ratio of $39 000 per quality-adjusted life year gained compared with strategy of unilateral common femoral, popliteal examination and no follow-up. |
| Samuel 2019 | USA; major academic tertiary care medical center | Quasi-experimental study; cost-effectiveness analysis | NR (only direct costs were considered) | 14 d; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | 157 adults underwent cranial or spinal surgical interventions; high-risk patients who present with brain injury and require surgical interventions | Routine ultrasound screening was compared with standard screening. | For diagnostic performance, detecting 1 DVT required 6 vs 27 ultrasound screening studies in the standard screening and the routine screening group, respectively. Total cost incurred per DVT diagnosis was lower for the standard screening approach ($13 664) versus the routine screening approach ($56 525). |
| Wilson 2005 | USA; inpatient stroke rehabilitation unit | Decision analytic model (decision tree); cost utility analysis | Societal | 4 y (life expectancy of those with ischemic stroke); no discount | $ (USD) in 2004 | Hypothetical patients with ischemic stroke at the time of admission to rehabilitation at risk of DVT; 12% | Two strategies were compared: (1) screening all patients with acute ischemic stroke for DVT by Doppler ultrasound; (2) clinical surveillance for signs of DVT and treatment after confirmation by Doppler ultrasound. | The expected health outcomes were 1.875 QALYs for ultrasound screening strategy and 1.872 QALYs for no screening strategy. The expected cost per patient was $330 for ultrasound screening strategy, compared with $162 for no screening. The ICER was estimated to be $67 200 per QALY gained. |
| Other | ||||||||
| Fuentes 2016 | Spain; hospital emergency room | Cross-sectional study; cost-effectiveness analysis | NR (only direct costs were considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | € in 2013 | 138 patients with symptoms of a first episode of DVT; consecutive patients (unselected patients, prevalence unknown) | The following strategies were compared: (1) current approach; (2) Oudega clinical probability algorithm; (3) Wells clinical probability algorithm. | Compared with current approach, the cost saving per patient was estimated to be €86.19 for Oudega clinical probability algorithm, and €97.40 for Wells clinical probability algorithm. |
| Hedderich 2019 | USA; emergency department | Decision analytic model (decision tree); cost utility analysis | US health care perspective | Lifetime horizon; 3% for both cost and effectiveness | $ (USD) in 2017 | Hypothetical patients admitted to the emergency department for possible CVT; low (1.6%) and high (50%) | The following strategies were compared: (1) NCCT; (2) NCCT plus CTV; (3) routine MRI; (4) routine MRI plus MRV. | Two strategies, NCCT and NCCT plus CTV were dominant over routine MRI and routine MRI plus MRV. NCCT plus CTV led to more QALYs (23.385 QALYs) compared with NCCT (23.374 QALYs), but also are more costly ($5210 for NCCT plus CTV versus $5057 for NCCT). Probabilistic sensitivity analysis found that CTV was the strategy with the highest percentage of cost-effective iterations if willingness-to-pay (WTP) thresholds were higher than $13 750/QALY. |
| Van Dam 2021 | Netherlands and Norway; emergency department | Decision analytic model; cost-effectiveness analysis | NR (only direct costs were considered) | 1 y; no discount (time horizon ≤ 1 y) | € in 2019 | Adult patients with suspected recurrent ipsilateral proximal DVT of the lower extremity on or off anticoagulant treatment; 43% (for recurrent DVT) | 13 diagnostic scenarios: (1) MRDTI only; (2) ultrasound (normal/abnormal) only; (3) ultrasound (positive/negative/inconclusive) only; (4) only ultrasound (normal/abnormal) in case of a likely clinical decision rule and/or abnormal D-dimer; (5) only ultrasound (positive/negative/inconclusive) in case of a likely clinical decision rule and/or abnormal D-dimer; (6) only MRDTI in case of an abnormal ultrasound; (7) only MRDTI in case of an inconclusive ultrasound; (8) only MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer; (9) only MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer and an abnormal ultrasound; (10) MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer and an inconclusive ultrasound; (11) Clinical decision rule and d-dimer; (12) treat all; (13) treat none | Total 1-y health care costs (€) per person and total mortality per 10 000 patients (1) MRDTI only: €1,271 and 18 deaths per 10 000 patients; (2) ultrasound (normal/abnormal) only: €1529 and 14 deaths per 10 000 patients; (3) ultrasound (positive/negative/inconclusive) only: €1378 and 15 deaths per 10 000 patients; (4) only ultrasound (normal/abnormal) in case of a likely clinical decision rule and/or abnormal D-dimer: €1365 and 16 deaths per 10 000 patients; (5) only ultrasound (positive/negative/inconclusive) in case of a likely clinical decision rule and/or abnormal D-dimer: €1278 and 17 deaths per 10 000 patients; (6) only MRDTI in case of an abnormal ultrasound: €1296 and 18 deaths per 10 000 patients; (7) only MRDTI in case of an inconclusive ultrasound: €1263 and 16 deaths per 10 000 patients; (8) only MRDTI in case of a likely clinical decision rule and/or abnormal D-Dimer: €1230 and 19 deaths per 10 000 patients; (9) only MRDTI in case of a likely clinical decision rule and/or abnormal D-Dimer and an abnormal ultrasound: €1260 and 19 deaths per 10 000 patients; (10) MRDTI in case of a likely clinical decision rule and/or abnormal D-dimer and an inconclusive ultrasound: €1219 and 17 deaths per 10 000 patients; (11) clinical decision rule and d-Dimer: €1654 and 14 deaths per 10 000 patients; (11) treat all: €2004 and 10 deaths per 10 000 patients; (13) treat none: 1239 and 104 deaths per 10 000 patients. Strategies with MRDTI for suspected recurrent ipsilateral DVT decreased 1-y health care costs compared with strategies without MRDTI, with similar impact on mortality. |
| CTPA for both PE and DVT | ||||||||
| Henschke 1994 | USA; not specified | Not specified (likely decision analytic model); cost-effectiveness analysis | NR (only direct cost of tests was considered) | NR, likely a short temporal horizon; no discount (time horizon ≤ 1 y) | $ (USD), currency year not specified | Hypothetical patients suspected with pulmonary embolism and DVT; unselected, prevalence unknown | Five strategies were compared: (1) angiogram; (2) radionuclide venography; (3) contrast venography; (4) sonography with Doppler; (5) radionuclide V/Q scan. | Effective cost, the money spent per unit of diagnostic information, was defined as the ratio of the expected direct test cost to its diagnostic performance. The effective cost was lowest for Doppler sonography, estimated to be between $378 and $486, followed by radionuclide leg venography ($843). The effective cost was estimated to be between $1557 and $2001 for contrast venography and $2061 for angiography, whereas the effective cost for radionuclide with V/Q scan depends on the prevalence of pulmonary embolism and morbidity and mortality cost. |
Abbreviations: MRV, magnetic resonance venography; NCCT, noncontrast computed tomography; NR, not reported; POC, point-of-care.
Currencies: Can$, Canadian dollar; €, Euros; ECU, European currency unit; FF, France franc; fl., Dutch guilders; £, UK Sterling; $, USD