Cost-avoidance associated with implementation of an overnight emergency medicine pharmacist at a Level I Trauma, Comprehensive Stroke Center.

AIM: To investigate the cost-avoidance associated with implementation of an overnight emergency medicine pharmacist (EMP) through documented clinical interventions. DESIGN: Retrospective evaluation of prospectively tracked interventions in a single Level I Trauma, Comprehensive Stroke Center, from November 25, 2020 through March 12, 2021 during expanded emergency medicine service hours (2300-0700). INTERVENTIONS: One of 45 clinical patient-care recommendations associated with cost-avoidance were available to be selected and documented by the EMP; more than one intervention was allowed per patient, though one clinical intervention could not be counted as multiple items. Documented services were associated with monetary cost avoidance based upon available literature assessing pharmacy clinical interventions. Differences in time from imaging to systemic thrombolytics and percentage of patients meeting door-to-alteplase benchmarks were compared with and without the availability of EMPs. RESULTS: Overnight EMPs documented 820 interventions during 107 overnight shifts with a cost avoidance of $612,974. The most common interventions were bedside monitoring (n = 127; $50,694), drug information consultation (97; $11,269), and antimicrobial therapy initiation and streamlining (95; $60,101). When categorizing interventions, 378 (46%; $292,484) were input as hands-on care, 216 (26%; $94,899) as individualization of patient care, 135 (17%; $25,897) as administrative and supportive tasks, 84 (10%; $121,746) as adverse drug event prevention, and 7 (1%; $77,964) as resource utilization. All patients (n = 6) with an acute ischemic stroke during the evaluation period received systemic thrombolytics ≤45 min in the presence of EMPs compared with 50% receiving thrombolytics ≤45 min without EMPs. CONCLUSIONS: Expanded overnight coverage by EMPs provided clinical bedside pharmacotherapy expertise to critically ill patients otherwise not available prior to study implementation. Clinical interventions were associated with substantial cost-avoidance.

Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.

Economic Evaluation of Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. METHODS: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0-2) and the extra cost per quality-adjusted life year gained. RESULTS: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, -$16 839 [95% CI, -$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%-22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04-0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. CONCLUSIONS: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695; Unique identifier: NL695. URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Genetic-guided pharmacotherapy for venous thromboembolism: a systematic and critical review of economic evaluations.

Despite the known contributions of genes, genetic-guided pharmacotherapy has not been routinely implemented for venous thromboembolism (VTE). To examine evidence on cost-effectiveness of genetic-guided pharmacotherapy for VTE, we searched six databases, websites of four HTA agencies and citations, with independent double-reviewers in screening, data extraction, and quality rating. The ten eligible studies, all model-based, examined heterogeneous interventions and comparators. Findings varied widely; testing was cost-saving in two base-cases, cost-effective in four, not cost-effective in three, dominated in one. Of 22 model variables that changed decisions about cost-effectiveness, effectiveness/relative effectiveness of the intervention was the most frequent, albeit of poor quality. Studies consistently lacked details on the provision of interventions and comparators as well as on model development and validation. Besides improving the reporting of interventions, comparators, and methodological details, future economic evaluations should examine strategies recommended in guidelines and testing key model variables for decision uncertainty, to advise clinical implementations.

Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke.

BACKGROUND AND PURPOSE: Tenecteplase improved functional outcomes and reduced the requirement for endovascular thrombectomy in ischemic stroke patients with large vessel occlusion in the EXTEND-IA TNK randomized trial. We assessed the cost-effectiveness of tenecteplase versus alteplase in this trial. METHODS: Post hoc within-trial economic analysis included costs of index emergency department and inpatient stroke hospitalization, rehabilitation/subacute care, and rehospitalization due to stroke within 90 days. Sources for cost included key study site complemented by published literature and government websites. Quality-adjusted life-years were estimated using utility scores derived from the modified Rankin Scale score at 90 days. Long-term modeled cost-effectiveness analysis used a Markov model with 7 health states corresponding to 7 modified Rankin Scale scores. Probabilistic sensitivity analyses were performed. RESULTS: Within the 202 patients in the randomized controlled trial, total cost was nonsignificantly lower in the tenecteplase-treated patients (40 997 Australian dollars [AUD]) compared with alteplase-treated patients (46 188 AUD) for the first 90 days(P=0.125). Tenecteplase was the dominant treatment strategy in the short term, with similar cost (5412 AUD [95% CI, -13 348 to 2523]; P=0.181) and higher benefits (0.099 quality-adjusted life-years [95% CI, 0.001-0.1967]; P=0.048), with a 97.4% probability of being cost-effective. In the long-term, tenecteplase was associated with less additional lifetime cost (96 357 versus 106 304 AUD) and greater benefits (quality-adjusted life-years, 7.77 versus 6.48), and had a 100% probability of being cost-effective. Both deterministic sensitivity analysis and probabilistic sensitivity analyses yielded similar results. CONCLUSIONS: Both within-trial and long-term economic analyses showed that tenecteplase was highly likely to be cost-effective for patients with acute stroke before thrombectomy. Recommending the use of tenecteplase over alteplase could lead to a cost saving to the healthcare system both in the short and long term. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388061.

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery.

OBJECTIVE: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data. METHODS: Medication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated. RESULTS: Using aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention. CONCLUSIONS: Apixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention.

Cost-effectiveness microsimulation of catheter-directed thrombolysis in submassive pulmonary embolism using a right ventricular function model.

Approximately 30-50% of hemodynamically stable patients presenting with acute pulmonary embolism (PE) have evidence of right ventricular (RV) dysfunction. These patients are classified as submassive PE and the role of reperfusion therapy remains unclear. We sought to identify the circumstances under which catheter-directed thrombolysis (CDT) would represent high-value care for submassive PE. We used a computer-based, individual-level, state-transition model with one million simulated patients to perform a cost-effectiveness analysis comparing the treatment of submassive PE with CDT followed by anticoagulation to treatment with anticoagulation alone. Because RV function impacts prognosis and is commonly used in PE outcomes research, our model used RV dysfunction to differentiate health states. One-way, two-way, and probabilistic sensitivity analyses were used to quantify model uncertainty. Our base case analysis generated an incremental cost-effectiveness ratio (ICER) of $119,326 per quality adjusted life year. Sensitivity analyses resulted in ICERs consistent with high-value care when CDT conferred a reduction in the absolute probability of RV dysfunction of 3.5% or more. CDT yielded low-value ICERs if the absolute reduction was less than 1.56%. Our model suggests that catheter-directed thrombolytics represents high-value care compared to anticoagulation alone when CDT offers an absolute improvement in RV dysfunction of 3.5% or more, but there is substantial uncertainly around these results. We estimated the monetary value of clarifying the costs and consequences surrounding RV dysfunction after submassive PE to be approximately $268 million annually, suggesting further research in this area could be highly valuable.

Financial Burden of Stroke Reflected in a Pilot Center for the Implementation of Thrombolysis.

Stroke represents a serious illness and is extremely relevant from the public health point of view, implying important social and economic burdens. Introducing new procedures or therapies that reduce the costs both in the acute phase of the disease and in the long term becomes a priority for health systems worldwide. The present study quantifies and compares the direct costs for ischemic stroke in patients with thrombolysis treatment versus conservative treatment over a 24-month period from the initial diagnosis, in one of the 7 national pilot centres for the implementation of thrombolytic treatment. The significant reduction (p < 0.001) of the hospitalization period, especially of the days in the intensive care unit (ICU) for stroke, resulted in a significant reduction (p < 0.001) of the total average costs in the patients with thrombolysis, both at the first hospitalization and for the subsequent hospitalizations, during the period followed in the study. It was also found that the percentage of patients who were re-hospitalized within the first 24-months after stroke was significantly lower (p < 0.001) among thrombolyzed patients. The present study demonstrates that the quick intervention in cases of stroke is an efficient policy regarding costs, of Romanian Public Health System, Romania being the country with the highest rates of new strokes and deaths due to stroke in Europe.

Cost-effectiveness of intrapleural use of tissue plasminogen activator and DNase in pleural infection: evidence from the MIST2 randomised controlled trial.

The MIST2 (Second Multicentre Intrapleural Sepsis Trial) trial showed that combined intrapleural use of tissue plasminogen activator (t-PA) and recombinant human DNase was effective when compared with single agents or placebo. However, the treatment costs are significant and overall cost-effectiveness of combined therapy remains unclear.An economic evaluation of the MIST2 trial was performed to assess the cost-effectiveness of combined therapy. Costs included were those related to study medications, initial hospital stay and subsequent hospitalisations. Outcomes were measured in terms of life-years gained. All costs were reported in euro and in 2016 prices.Mean annual costs were lowest in the t-PA-DNase group (EUR 10 605 for t-PA, EUR 17 856 for DNase, EUR 13 483 for placebo and EUR 7248 for t-PA-DNase; p=0.209). Mean 1-year life expectancy was 0.988 for t-PA, 0.923 for DNase, and 0.969 for both placebo and t-PA-DNase (p=0.296). Both DNase and placebo were less effective, in terms of life-years gained, and more costly than t-PA. When placebo was compared with t-PA-DNase, the incremental cost per life-year gained of placebo was EUR 1.6 billion, with a probability of 0.85 of t-PA-DNase being cost-effective.This study demonstrates that combined t-PA-DNase is likely to be highly cost-effective. In light of this evidence, a definitive trial designed to facilitate a thorough economic evaluation is warranted to provide further evidence on the cost-effectiveness of this promising combined intervention.

Retrospective comparison of ultrasound facilitated catheter-directed thrombolysis and systemically administered half-dose thrombolysis in treatment of pulmonary embolism.

This study retrospectively compared the outcomes of patients who received ultrasound facilitated catheter-directed thrombolysis (UFCDT) versus systemically administered 'half-dose' thrombolysis (HDT) in 97 patients with PE. The outcomes assessed included changes in baseline pulmonary artery systolic pressure (PASP), right ventricle/left ventricle ratio (RV/LV), cost and duration of hospitalization, death, bleeding, and recurrent venous thromboembolism in the short and intermediate term follow-up. Analyses were performed using a covariance adjustment propensity score approach to address baseline differences between groups in variables associated with PASP and RV/LV, covarying baseline scores. The baseline mean ± SE PASP dropped from 49.3 ± 1.1 to 32.5 ± 0.3 mmHg at 36 hours in the HDT group, and from 50.6 ± 1.2 to 35.1 ± 0.4 mmHg in the UFCDT group; group × time interaction p-value = 0.007. Corresponding drops in the RV/LV were from a baseline of 1.26 ± 0.05 to 1.07 ± 0.01 in the HDT group and from 1.30 ± 0.05 to 1.14 ± 0.01 in the UFCDT group at 36 hours; group × time interaction p-value = 0.269. Statistically significant decreases were noted in PASP and RV/LV for both the HDT and UFCDT at 36 hours and follow-up. PASP through follow-up was significantly lower in the HDT than the UFCDT group. Likewise, RV/LV was lower in the HDT group. The duration and cost of hospitalization were lower in the HDT group (6.2 ± 1.4 days vs 1.9 ± 0.3 days, p < 0.001; US$12,000 ± $3000 vs $74,000 ± $6000, p < 0.001). We conclude that both UFCDT and HDT lead to rapid reduction of PASP and RV/LV, whereas HDT leads to a lower duration and cost of hospitalization.

Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters.

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.

Cost-Utility Analysis of Apixaban versus Warfarin in Atrial Fibrillation Patients with Chronic Kidney Disease.

BACKGROUND: Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function. OBJECTIVES: To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function. METHODS: A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings. CONCLUSIONS: Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment.

Impact of cost on use of non-vitamin K antagonists in atrial fibrillation patients in Ontario, Canada.

Canadian guidelines recommend non vitamin K antagonists (NOACs) in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF), but NOACs are more expensive than VKAs. Canada has a universal healthcare system that covers the cost of NOACs for select patient groups. Ability to pay for NOACs may influence their use. We reviewed medical charts of Hamilton General Hospital outpatients under the age of 65 with a new diagnosis of AF who were referred for initiation of OAC therapy. We contacted these patients by phone and asked them to complete a questionnaire regarding their OAC choice, economic factors that may have influenced this choice (income, insurance) and the financial burden of OAC therapy. We included 110 patients, mean age 56 years, and 26.4% females. NOAC users had a higher median neighborhood income than VKA users (p = 0.0144, n = 110). 73 patients responded to the questionnaire. NOAC users reported higher annual household income (p = 0.0038, n = 73). Patients with private insurance were more likely to use NOACs than those without insurance (p = 0.0496, n = 73). The cost of NOACs and ability to pay is a determinant of their use Ontario patients under the age of 65. This two tiered provision of care appears to contradict the values of Canada's universal healthcare system.

Catheter-Directed Thrombolysis Versus Pharmacomechanical Thrombectomy for Upper Extremity Deep Venous Thrombosis: A Cost-Effectiveness Analysis.

BACKGROUND: Upper extremity deep vein thrombosis represents (UEDVT) 2-3% of all deep vein thrombosis. Catheter directed thrombolysis (CDT) was replaced largely by pharmacomechanical thrombolysis (PMT) in our institution. In this study we compared the immediate and 1-year results as well as the total hospital costs between CDT and PMT in the treatment of UEDVT. METHODS: From 2006 to 2013, 55 patients with UEDVT were treated with either CDT or PMT at Helsinki University Hospital. Of them, 43 underwent thoracoscopic rib resection later to relieve phlebography-confirmed vein compression. This patient cohort was prospectively followed up with repeated phlebographies. CDT was performed to 24 patients, and 19 had PMT with a Trellis™ device. Clinical evaluation and vein patency assessment were performed with either phlebography or ultrasound 1 year after the thrombolysis. Primary outcomes were immediate technical success, 1-year vein patency, and costs of the initial treatment. RESULTS: The immediate overall technical success rate, defined as recanalization of the occluded vein and removal of the fresh thrombus, was 91.7% in the CDT group and 100% in the PMT group (n.s.). The median thrombolytic time was significantly longer in CDT patients than that in PMT patients (21.1 vs. 0.33 hr, P < 0.00001). There were no procedure-related complications. The 1-year primary assisted patency rate was similar in both the groups (91.7% and 94.7%). There were no recurrences of clinical DVT. The hospital costs for the acute period were significantly lower in the PMT group than those in the CDT group (medians: 11,476 € and 5,975 € in the CDT and PMT groups, respectively [P < 0.00001]). CONCLUSIONS: The clinical results of the treatment of UEDVT with CDT or PMT were similar. However, PMT required shorter hospital stay and less intensive surveillance, leading to lower total costs.

Cost of Alteplase Has More Than Doubled Over the Past Decade.

BACKGROUND AND PURPOSE: Intravenous alteplase (tissue-type plasminogen activator) has been shown to be cost-effective because of savings in long-term disability. In October of 2005, an increased DRG payment to hospitals for alteplase-treated stroke patients was introduced. We sought to describe the trends in the cost of alteplase over time, in comparison to trends in hospital reimbursement in the United States. METHODS: Using publicly available information on the Centers for Medicare and Medicaid Services (CMS) website (www.cms.gov), we obtained CMS quarterly payment amounts between January 1, 2005, and October 1, 2014, for alteplase, listed as alteplase recombinant, per mg. CMS payment amounts are the manufacturer's average sales price+6% until April 2014, when it was lowered to +4.3%. Estimates for DRG base payments were calculated within the Medicare Provider and Analysis Review (MEDPAR) for fiscal years 2006 (DRG 559) and 2013 (MS DRGs 61, 62, and 63) as (DRG relative weights)×(standardized operating and capital amount). The consumer price index was also queried for all prescription drugs, urban areas, during the same study period as reference. RESULTS: The CMS payment amount for alteplase per milligram was $30.50 in January 2005 and $64.30 in October 2014. Trends in the CMS payment amounts for alteplase increased by 111% between 2005 and 2014. The consumer price index for all prescription drugs increased by 30.2% in the same time frame. The base payment for alteplase-treated stroke admissions was $11 173 in 2006 and $12 064 in 2013, an 8% increase. CONCLUSIONS: We found a striking increase in the cost of alteplase over the last decade, with a 100 mg vial now with a CMS payment of ≈$6400, a >100% increase over 10 years. During the same time frame, the DRG base payment to hospitals increased by only 8%, and alteplase cost increased from 27% of the payment in 2006 to 53% in 2013. Researchers and stroke physicians should be aware of these changes in drug costs and their impact on cost-effectiveness analyses.

Defibrotide in Severe Sinusoidal Obstruction Syndrome: Medicine and Economic Issues.

In Europe, Defitelio (defibrotide) has a Market Authorization in curative treatment of severe sinusoidal obstruction syndrome (SOS) but not in prophylaxis (2013). In France, defibrotide has had a compassionate-use program since 2009. Today, the high cost of defibrotide remains a major hurdle for hospital budgets. Medicine and economic issues were evaluated for the 39 hospitals of the French Public Assistance-Hospitals of Paris (AP-HP). We analyzed literature reviews, consumption, and expenditures through AP-HP data in 2014 and patient profiles with defibrotide in the corresponding diagnostic-related groups (DRGs) and consulted a board of hematologists. Finally, 18 publications were selected. Between 2011 and 2014 consumption increased to €5.2M. In 2014, 80 patients receiving defibrotide were mainly ascribed to the DRG "hematopoietic stem cell transplantation" levels 3 or 4. The tariffs attributed to drugs (€3544 to 4084) cover a small part of treatment costs (€97,524 for an adult). French experts thus recommended a harmonization of indications in prophylaxis (off-label use), improvement of pretransplant care, and optimization of the number of vials used. The economic impact led experts to change their practices. They recommended the restriction of defibrotide use to SOS curative treatment and to high-risk situations in prophylaxis.

Would a Large tPA Trial for Those 4.5 to 6.0 Hours from Stroke Onset Be Good Value for Information?

OBJECTIVES: To quantify the potential value of new research in patients treated with thrombolytic treatment (tissue-type plasminogen activator [tPA]) in the 4.5- to 6.0-hour time window after stroke onset and to determine the optimal size of a future trial using value of information analysis. METHODS: Expected value of partial perfect and sample information (EVPPI and EVSI) analyses were conducted using a probabilistic Markov model. Data for modified Rankin Scale (mRS) distributions in patients 4.5 to 6.0 hours since stroke onset for tPA (n = 576) and placebo (n = 543) were obtained from pooled randomized controlled trials. EVSI was quantified with net monetary benefit (assuming willingness to pay for health as $100,000/QALY). We calculated discounted population-level EVSI by multiplying per-person EVSI by the annual number of eligible patients with stroke in the United States and assuming a 10-year time frame of treatment use. Study costs were based on administrative costs and the costs of tPA. RESULTS: The base-case lifetime cost-effectiveness analysis showed that tPA was dominated by placebo in this patient group. EVPPI for mRS distributions was $1003 per person. On the basis of EVSI, the optimal sample size of a new trial collecting data on tPA efficacy in these patients would be 5600 across study arms with expected population-level societal returns (EVSI minus study costs) of $68.7 million. CONCLUSIONS: Expanding research attention to the 4.5- to 6.0-hour time window for tPA treatment of patients with acute ischemic stroke is justified because the expected returns are substantial. Even a relatively large trial in which more information on treatment efficacy on the basis of mRS scores is collected would represent good value for information.

Financial burden of survivors of medically-managed myocardial infarction and its association with selected social determinants and quality of life in a lower middle income country.

BACKGROUND: Burden from ischemic heart disease is rising in Sri Lanka due to the demographic and epidemiological transitions. Documented literature is scarce on quality of life, financial burden and its determinants in relation to myocardial infarction (MI). This study was done to describe the financial burden among the survivors of MI managed only with drugs (i.e. those who did not undergo Percutaneous Coronary Intervention or Coronary Artery Bypass Graft) and its association with selected social determinants (SDHs) and quality of life (QOL). METHODS: A cross sectional study was done among MI survivors in 13 hospitals in the premier province of Sri Lanka. Out of 336 participants recruited at hospital stay, 270 responded through a self-administered questionnaire at 1 month post discharge. Questionnaire included sections on financial burden, selected SDHs and on QOL measured by the EQ-5D-3 L QOL tool. Presence of financial burden was determined using an operational definition. Associations were tested with Mann-Whitney-U test, Chi square test and Spearman-correlation-coefficient at 5% significant level. RESULTS: Around 40% (n = 116) had to seek financial support for out-of-pocket expenditure. Nearly 5% (n = 6) of previously employed participants had lost their job. Of the employed respondents (n = 139, 51.5%), 29% (n = 85) had limited physical activity and 40% (n = 115) had limitations of employment time. Of the respondents, 15.4% had to apply for a loan, 7.8% had to sell a property, 19.1% had an income loss and 33.8% had to restrict usual expenses. Financial burden was not significantly associated with gender (p = 0.146), ethnicity (p = 0.068), highest education (p = 0.184) and area of residence (p = 0.369). Influence of income (p = 0.001), social support (p = 0.002) and the health infrastructure (p < 0.001) were significantly associated with the occurrence of a financial burden. In the group with a financial burden, the index score (p = 0.002) and VAS score (p < 0.001) of EQ-5D-3 L were significantly lower. CONCLUSIONS: Financial burden is common among survivors of medically-managed occurring irrespective of the gender, ethnicity, education and the area. It is influenced significantly by the income, level of social support and the level of health infrastructure. The financial burden is influencing the post-discharge-1-month QOL.

Cost-Effectiveness of a National Opportunistic Screening Program for Atrial Fibrillation in Ireland.

OBJECTIVES: To evaluate the cost-effectiveness of a national atrial fibrillation screening program in Ireland involving annual opportunistic pulse palpation of all those older than 65 years during general practitioner consultations, with an electrocardiogram being performed if an irregular pulse is detected. METHODS: A probabilistic Markov model was used to simulate costs and clinical outcomes in a hypothetical cohort of men and women with and without screening over the course of 25 years, using a societal perspective. RESULTS: Screening was associated with an incremental cost-effectiveness ratio of €23,004/quality-adjusted life-year compared with routine care. Nevertheless, if the relative risk of stroke and systematic embolism in screen-detected patients is more than 12% lower than that in patients with atrial fibrillation identified through routine practice, then screening would not be considered cost-effective at a willingness-to-pay threshold of €45,000/quality-adjusted life-year. An analysis comparing alternative combinations of start age and screening interval found that less frequent screening with a later start age may be more cost-effective than an annual screening from age 65 years. CONCLUSIONS: Annual opportunistic screening of men and women aged 65 years and older in primary care in Ireland is likely to be cost-effective using conventional willingness-to-pay thresholds, assuming that those detected through screening have a comparable stroke risk profile as those detected through routine practice. Raising the start age of screening or increasing the screening interval may improve the cost-effectiveness of a prospective screening program.

Physician and Patient Preferences for Nonvalvular Atrial Fibrillation Therapies.

OBJECTIVES: The objective of this study was to compare patient and physician preferences for different antithrombotic therapies used to treat nonvalvular atrial fibrillation (NVAF). METHODS: Patients diagnosed with NVAF and physicians treating such patients completed 12 discrete choice questions comparing NVAF therapies that varied across five attributes: stroke risk, major bleeding risk, convenience (no regular blood testing/dietary restrictions), dosing frequency, and patients' out-of-pocket cost. We used a logistic regression to estimate the willingness-to-pay (WTP) value for each attribute. RESULTS: The 200 physicians surveyed were willing to trade off $38 (95% confidence interval [CI] $22 to $54] in monthly out-of-pocket cost for a 1% (absolute) decrease in stroke risk, $14 (95% CI $8 to $21) for a 1% decrease in major bleeding risk, and $34 (95% CI $9 to $60) for more convenience. The WTP value among 201 patients surveyed was $30 (95% CI $18 to $42) for reduced stroke risk, $16 (95% CI $9 to $24) for reduced bleeding risk, and -$52 (95% CI -$96 to -6) for convenience. The WTP value for convenience among patients using warfarin was $9 (95% CI $1 to $18) for more convenience, whereas patients not currently on warfarin had a WTP value of -$90 (95% CI -$290 to -$79). Both physicians' and patients' WTP value for once-daily dosing was not significantly different from zero. On the basis of survey results, 85.0% of the physicians preferred novel oral anticoagulants (NOACs) to warfarin. NOACs (73.0%) were preferred among patients using warfarin, but warfarin (78.2%) was preferred among patients not currently using warfarin. Among NOACs, both patients and physicians preferred apixaban. CONCLUSIONS: Both physicians and patients currently using warfarin preferred NOACs to warfarin. Patients not currently using warfarin preferred warfarin over NOACs because of an apparent preference for regular blood testing/dietary restrictions.