Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Cost-Effectiveness Study.

BACKGROUND: Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE). OBJECTIVE: To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients with a first unprovoked VTE. DESIGN: Markov modeling study. DATA SOURCES: Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events. TARGET POPULATION: Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment. TIME HORIZON: Lifetime. PERSPECTIVE: Canadian health care public payer. INTERVENTION: Indefinite anticoagulation with direct oral anticoagulants. OUTCOME MEASURES: Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs). RESULTS OF BASE-CASE ANALYSIS: When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person). RESULTS OF SENSITIVITY ANALYSIS: Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation. LIMITATION: The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation. CONCLUSION: Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Protocol for a modelling study to assess the clinical and cost-effectiveness of indefinite anticoagulant therapy for first unprovoked venous thromboembolism.

INTRODUCTION: Deciding whether to stop or extend anticoagulant therapy indefinitely after completing at least 3 months of initial treatment for a first unprovoked venous thromboembolism (VTE) remains a challenge for clinicians, patients and policy makers. Guidelines suggest an indefinite duration of anticoagulant therapy in these patients, yet its benefits, harms and costs have not been formally assessed. The aim of this proposed modelling study is to assess the differences in clinical benefits, harms and costs of stopping versus continuing anticoagulant therapy indefinitely for a first unprovoked VTE. METHODS AND ANALYSIS: We will develop a probabilistic Markov model, adopting a 1-month cycle length and a lifetime horizon, to estimate life-years, quality-adjusted life-years, costs and the incremental cost-effectiveness ratios for a simulated population of patients with a first unprovoked VTE who will receive indefinite duration of anticoagulant therapy versus a population who will not receive extended treatment after completing 3 months of initial anticoagulant therapy. The economic evaluation will adopt a third-party payer perspective relating to a Canadian publicly funded healthcare system. Estimates for the probability of relevant clinical events will be informed by systematic reviews and meta-analyses, while costs and utility values will be obtained from published Canadian sources. Stratified analyses based on sex, age and site of initial VTE will also be performed to identify subgroups of patients with a first unprovoked VTE in whom continuing anticoagulant therapy indefinitely might prove to be clinically beneficial and cost-effective over stopping treatment. We will also conduct sensitivity and scenario analyses to assess robustness of study findings to changes in individual or groups of key parameters. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study. The results will be disseminated through presentations at relevant conferences and in a manuscript that will be submitted to a peer-reviewed journal.

A novel approach to needs assessment in curriculum development: going beyond consensus methods.

BACKGROUND: Needs assessment should be the starting point for curriculum development. In medical education, expert opinion and consensus methods are commonly employed. AIM: This paper showcases a more practice-grounded needs assessment approach. METHODS: A mixed-methods approach, incorporating a national survey, practice audit, and expert consensus, was developed and piloted in thrombosis medicine; Phase 1: National survey of practicing consultants, Phase 2: Practice audit of consult service at a large academic centre and Phase 3: Focus group and modified Delphi techniques vetting Phase 1 and 2 findings. RESULTS: Phase 1 provided information on active curricula, training and practice patterns of consultants, and volume and variety of thrombosis consults. Phase 2's practice audit provided empirical data on the characteristics of thrombosis consults and their associated learning issues. Phase 3 generated consensus on a final curricular topic list and explored issues regarding curriculum delivery and accreditation. CONCLUSIONS: This approach offered a means of validating expert and consensus derived curricular content by incorporating a novel practice audit. By using this approach we were able to identify gaps in training programs and barriers to curriculum development. This approach to curriculum development can be applied to other postgraduate programs.

Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis.

BACKGROUND: To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery. METHODS: Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding. RESULTS: The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement. CONCLUSIONS: Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance.

VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies.

Clinical outcome studies have shown that it is safe to withhold anticoagulant therapy in patients with suspected pulmonary embolism (PE) who have a negative D-dimer result and a low pretest probability (PTP) either using a PTP model or clinical gestalt. It was the objective of the present study to assess the safety of the combination of a negative VIDAS D-dimer result in combination with a non-high PTP using the Wells or Geneva models to exclude PE. A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Seven studies (6 prospective management studies and 1 randomised controlled trial) reporting failure rates at three months were included in the analysis. Non-high PTP was defined as "unlikely" using the Wells' model, or "low/intermediate" PTP using either the Geneva score, the Revised Geneva Score, or clinical gestalt. Two reviewers independently extracted data onto standardised forms. A total of 5,622 patients with low/intermediate or unlikely PTP were assessed using the VIDAS D-dimer. PE was ruled out by a negative D-dimer test in 2,248 (40%, 95% confidence intervals [CI] 38.7 to 41.3%) of them. The three-month thromboembolic risk in patients left untreated on the basis of a low/intermediate or unlikely PTP and a negative D-dimer test was 3/2,166 (0.14%, 95% CI 0.05 to 0.41%). In conclusion, the combination of a negative VIDAS D-dimer result and a non-high PTP effectively and safely excludes PE in an important proportion of outpatients with suspected PE.

The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism.

INTRODUCTION: Pretest probability assessment and objective testing are combined to appropriately manage patients with suspected pulmonary embolism (PE). However, the interobserver reliability of pretest probability assessment has not been investigated. We sought to determine (for patients with suspected PE) the interobserver reliability of pretest probability assessment (by overall impression (gestalt) versus an explicit clinical model). MATERIALS AND METHODS: A prospective cohort study was conducted at an urban university hospital. For patients referred for ventilation and perfusion (V/Q) scanning for suspected PE, structured assessments (11 history and 4 physical examination parameters) were performed by a referring physician and a designated thrombosis physician. The referring and thrombosis physicians also assigned a pretest probability for PE (low, moderate, or high) by gestalt. An explicit seven-point clinical model for suspected PE was later applied to each structured assessment to determine the pretest probability. Assessments were performed independently and prior to diagnostic test results. Interobserver reliability (two rater unweighted Kappa (kappa) statistic) was determined for each parameter on the structured assessment and the pretest probability assessments (gestalt vs. explicit clinical model). RESULTS: One hundred and ten patients with suspected PE received duplicate assessments. Historical features demonstrated substantial to almost perfect interobserver reliability (kappa=0.60-0.95). For the physical findings, only heart rate had substantial interobserver reliability (kappa=0.60). Pretest probability assessment was not reliable when using physician's gestalt (kappa=0.33), but produced substantial interobserver reliability using the explicit clinical model (kappa=0.62). CONCLUSIONS: Given the inadequate interobserver reliability of pretest probability assessment by overall impression (or gestalt), physicians should use explicit clinical models in the diagnostic management of patients with suspected pulmonary embolism.

Shifting from inpatient to outpatient treatment of deep vein thrombosis in a tertiary care center: a cost-minimization analysis.

STUDY OBJECTIVE: To compare the cost of contemporary outpatient and historical inpatient management of proximal lower limb deep vein thrombosis (DVT) in adults. DESIGN: Prospective, observational study with historical inpatient cases as controls. SETTING: Ambulatory thrombosis clinic of a tertiary care teaching center in Canada. PATIENTS: Forty-nine inpatients with DVT from a previous study in 1996 at the same institution who would have been eligible for outpatient therapy if this option had been available, and 51 consecutive patients referred to the ambulatory thrombosis clinic for treatment of DVT between March 2000 and January 2001. INTERVENTION: The 49 inpatients received unfractionated heparin, and the 51 outpatients received low-molecular-weight heparin (LMWH). MEASUREMENTS AND MAIN RESULTS: A cost-minimization analysis restricted to the hospital perspective was conducted. This design was justified based on the clinical equivalence of the two treatment strategies. All direct hospital costs for treating the 51 consecutive outpatients with LMWH were measured. These data were compared with the cost of treating the inpatients with unfractionated heparin. The analysis horizon was limited to 7 days, based on the duration of hospitalization and length of heparin therapy for DVT before conversion to oral warfarin. The mean cost (in Canadian dollars) per outpatient case was 248 Canadian dollars (95% confidence interval 216-280 Canadian dollars) and was significantly different from the mean cost/inpatient case of 2826 Canadian dollars (adjusted for the difference in fiscal years) (p<0.0005). A breakdown of the outpatient cost showed that nursing time contributed to 51% of the cost, monitoring laboratory tests 5%, drugs 2%, and other costs (diagnostic laboratory tests and medical imaging) 42%. CONCLUSION: Converting from inpatient to outpatient treatment of proximal DVT was associated with a significant cost savings for our institution. Accordingly, it is financially advantageous for hospitals to offer this service as it reduces direct costs and does not appear to compromise patient care.

The outpatient treatment of deep vein thrombosis delivers cost savings to patients and their families, compared to inpatient therapy.

BACKGROUND: The outpatient treatment of deep vein thrombosis (DVT) with low-molecular-weight heparin (LMWH) has been shown to be cost-effective from the perspective of a third party payer. The aim of this study is to determine if some or all of these cost savings to third party payers are shifted to patients and their families. METHODS: A prospective cohort study with micro-costing of patient/family costs was conducted at the thrombosis units of The Ottawa Hospital. Costs were determined by administering a questionnaire at the end of the patients' heparin therapy. Over a period of 4 months, consecutive patients presenting at the thrombosis units were approached at the initiation of their heparin therapy; 44 patients consented to participate and completed questionnaires were obtained for 41. RESULTS: The mean patient/family costs associated with outpatient therapy were significantly less than those associated with inpatient therapy (219.42 dollars versus 402.93 dollars, p=0.003); a savings of 190.91 dollars per patient. Even when lost income to patients/families was ignored, mean patient/family costs remained significantly less for outpatient therapy (72.00 dollars versus 134.29 dollars, p=0.004); a savings of 62.30 dollars per patient. Furthermore, patients preferred outpatient to inpatient therapy by almost 3:1 (30 versus 11, respectively). INTERPRETATION: The outpatient treatment of DVT does not result in any net shifting of costs to patients and their families, and further, brings about cost savings. Given the cost savings associated with and the preference of patients for outpatient care, this study further supports the shift of DVT therapy from the inpatient unit to the outpatient clinic.