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Aims The Angiotensin Receptor-Neprilysin Inhibitor sacubitril-valsartan (ARNI) and dapagliflozin, a sodium-glucose transport protein 2 inhibitor, reduce the risk of heart failure hospitalization (hHF) and cardiovascular (CV) mortality in patients with reduced ejection fraction (HFrEF). Their comparative value for money is undetermined. Therefore, our aim was to compare the cost per outcome implications of utilizing dapagliflozin vs. ARNI for preventing heart failure (HF) events of non-diabetic patients with HFrEF. Methods and results We calculated the cost needed to treat (CNT) to prevent one HF event. The cost needed to treat was estimated by multiplying the annualized number needed to treat (NNT) to prevent one event by each therapy’s annual cost. Efficacy estimates were extracted from published secondary analyses of non-diabetic patients in DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2020 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the trial’s populations and drug costs in various countries. The annualized NNT to prevent one HF event for dapagliflozin was 31 (95% CI 21–71) vs. 33 (95% CI 24–62) for ARNI. The CNT of dapagliflozin in the US is $141 112 (95% CI $95 592–$323 192) compared to $158 169 (95% CI $115 032–$297 166) for sacubitril-valsartan. The CNT results were sensitive to drug costs in various countries. Conclusion Dapagliflozin and ARNI provide comparable value for money for preventing HF events in non-diabetic patients with HFrEF. In healthcare settings where dapagliflozin’s price is significantly lower than ARNI, it provides superior value for money.

Background: The RS assay is widely used in ER+ HER2-negative BC to guide treatment decisions. In TAILORx, RS distribution was similar in blacks vs whites and in Hispanics vs non-Hispanics. Also, TAILORx analyses revealed similar results across ethnic groups with endocrine therapy being consistently noninferior to chemotherapy (CT) plus endocrine therapy in RS 11-25 pts. We investigated RS distribution among Jewish vs Arab/Druze pts who underwent RS testing through Clalit Health Services (CHS), the largest HMO in Israel, as well as differences in CT use and clinical outcomes between these 2 ethnic groups. Methods: The RS distribution analysis included all CHS pts (regardless of nodal status) who were tested between 1/2006 and 2/2019. For the clinical outcomes analysis, we employed a dataset used in prior analyses (Stemmer et al, poster# 249, SG-BCC 2019) of node-negative pts who were tested between 1/2006 and 12/2009, and as such, it is a subset of the cohort used for the RS distribution analysis. The study was approved by the IRB of the CHS Community Division and was granted a waiver for obtaining pt consent. Results: The RS distribution analysis involved 9054 pts who were tested in the evaluated timeframe and for whom RS results and ethnicity information were available. These included 8223 (91%) Jews and 831 (9%) Arabs/Druze, approximately reflecting the proportion of BC cases diagnosed in the respective ethnic groups. The 2 groups were similar in their baseline pt/tumor characteristics except for age and tumor size (Table). RS distribution was also similar between the 2 ethnic groups (Table). The subset of node-negative pts for whom treatment and clinical outcomes are known included 1274 (93%) Jewish pts and 91 (7%) Arab/Druze pts. In this subset, the only statistically significant difference in pt/tumor characteristics between the ethnic groups was age (median [interquartile range]) of 60 [53-66] yrs in the Jewish pts vs 55 [48-63] yrs in the Arab/Druze pts; P=.0004), similar to the complete cohort. The RS distribution was similar to that in the larger cohort, with no significant differences between the ethnic groups (P=.75). Also, CT use was consistent with the RS result in both ethnic groups, and was overall somewhat higher among Arab/Druze pts (25% vs 19%), due primarily to higher CT use among Arabs/Druze pts in the largest RS category (11-25), in which significant differences with respect to age were noted (median [interquartile range], 59 [52-66] yrs in Jewish pts vs 52 [46-61] yrs in Arab/Druze pts; P Conclusions: RS distribution and clinical outcomes were similar in Jewish and Arab/Druze BC pts. Arab/Druze pts undergoing RS testing were overall younger than the Jewish pts, which may suggest under-diagnosis and/or under-testing in the older Arab/Druze pt population. Also, CT use seemed higher in the Arab/Druze pt population, possibly reflecting the differences in the age distribution between these ethnic groups. Table: Patient/tumor characteristics by ethnicityJewsArabs/DruzeP valuen = 8223n = 831Female, n (%)8132 (98.9%)825 (99.3%).3Median (interquartile range) age, years62 (53-68)55 (48-64)1 - 2 cm4233 (51.5%)411 (49.5%)>22153 (26.2%)302 (36.3%)Unknown123 (1.5%)6 (0.7%)Tumor grade category, n (%).12Grade 11109 (13.4%)123 (14.8%)Grade 24192 (51.0%)443 (53.3%)Grade 31389 (16.9%)120 (14.4%)Not applicable/Unknown1533 (18.6%)145 (17.4%)Histology, n (%).92IDC6530 (79.4%)665 (80.0%)ILC1113 (13.5%)113 (13.6%)Papillary79 (1.0%)10 (1.2%)Mucinous/colloid144 (1.8%)16 (1.9%)Other/unknown357 (4.3%)27 (3.2%)Recurrence Score category, n (%).170-101612 (19.6%)176 (21.2%)11-255091 (61.9%)522 (62.8%)26-1001520 (18.5%)133 (16.0%) Citation Format: Gil Bar Sela, Yousef Samih, Rinat Yerushalmi, Michelle Leviov, Noa Efrat Ben-Baruch, Iryna Kuchuk, Margarita Tokar, Tamar Peretz, Amir L Sonnenblick, Lior Soussan-Gutman, Avital Bareket-Samish, Georgeta Fried, Shani Paluch-Shimon, Bella Kaufman, Ariel Hammerman, Nicky Liebermann, Salomon M Stemmer. Ethnicity, recurrence score (RS) distribution, and clinical outcomes in ER+ HER2-negative breast cancer (BC) patients (pts) in Israel [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-16.

Background Comorbid heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (DM) is associated with a very high risk of HF events. Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, improve HF outcomes in these patients, but their comparative value for money in this patient population has not yet been determined. Objective We aimed to compare the cost needed to treat (CNT) to avoid an HF event with each drug. Methods CNT was estimated by multiplying the annualized number needed to treat (NNT) to prevent one HF event by the annual cost of each therapy. HF events were defined as the first event of hospitalization for HF or cardiovascular mortality. Drug efficacy data were extracted from published secondary analyses of patients with DM in the DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2021 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed on parameters that may have affected the CNT. Results The annualized NNT was 24 (95% confidence interval [CI] 16-54) for dapagliflozin and 57 (95% CI 31-433) for the ARNI. At an annual cost of $US4523 and 5099, respectively, the CNT was $US108,563 (95% CI 72,375-244,267) for dapagliflozin and $US290,671 (95% CI 158,084-2,208,079) for the ARNI. Conclusions Dapagliflozin seems to offer greater value for money than the ARNI for patients with HFrEF and DM. Our results provide support for contemporary guidelines advocating the use of dapagliflozin in these patients.

ObjectivesWe aimed to examine clinical data and baseline blood test results as potential predictive biomarkers for benefit from nivolumab, in advanced non-small cell lung cancer patients (NSCLC).Materials and MethodsA chart review was performed of 108 advanced NSCLC patients who commenced treatment with nivolumab between 2015-6 at three Israeli cancer centers, and for whom laboratory tests results were available. Data collected included sex, age, ECOG-PS, histology and number of previous lines of treatment. Baseline blood test results collected: absolute lymphocyte and neutrophil count (ANC), white blood cells (WBC), hemoglobin, platelets, albumin and lactate dehydrogenase (LDH). Neutrophil to Lymphocyte Ratio and ‘derived NLR’ (dNLR = (ANC/[WBC-ANC])) were calculated. Disease control at six months (DC6) was defined as any tumor shrinkage or stable disease during the first six months of nivolumab treatment. The association between clinical/laboratory variables and survival was tested with a Cox proportional hazard model. Data cut-off occurred in November 2019.Results35 patients (32.4%) achieved DC6. Median overall survival (OS) of entire study population was 5.4 months. Four year survival rate was 16%. Achievement of DC6 strongly correlated with longer OS (HR 0.12, 95% C.I. 0.07-0.21, pConclusionIn real-life setting, long-term efficacy of nivolumab in advanced line treatment of NSCLC is consistent with clinical trials. Response or stability of disease during first six months of treatment is associated with prolonged survival. We propose a novel score (CLAS) that may be useful for predicting outcome in nivolumab-treated NSCLC patients, but further validation is required.

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, canagliflozin, and dapagliflozin reduce the risk of heart failure (HF) events in patients with diabetes mellitus (DM) at high risk for HF. Differences in HF outcomes between SGLT2i were demonstrated in a recent-published meta-analysis. Nevertheless, comparative cost-effectiveness analyses of SGLT2i provided for this indication have not been published yet. Therefore, we aimed to provide a preceding economic comparison of the costs required for improving HF outcomes by these three SGLT2i. The primary outcome was the cost needed to treat (CNT) to prevent one event of hospitalization for HF or cardiovascular mortality. CNT is calculated by multiplying the annualized number needed to treat to prevent one event by the annual cost of therapy. Clinical outcome data were extracted from pre-specified cohorts of HF-naive patients in the pivotal randomized controlled trials (RCTs). Costs of interventions were estimated as 75% of the US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the RCT's populations. We figured the CNT for the primary prevention of HF events in DM patients to be $542,328 ($409,044-$905,412) for empagliflozin, $2,347,488 ($1,066,208-∞) for canagliflozin and $2,128,374 ($1,204,740-$48,140,518) for dapagliflozin. Sensitivity analysis confirmed the cost benefit of empagliflozin. Our findings suggest that between the available SGLT2i, the cost of primary prevention of HF in patients with DM at high risk for HF is lowest with empagliflozin. These findings may help choose an SGLT2i until head-to-head RCTs, and comprehensive cost-effective analyses for this indication are available.

Introduction: The Glucagon-Like Peptide-1 receptor agonists (GLP-1a) semaglutide, dulaglutide, and liraglutide reduce major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus ( T2DM) and established CVD. The American Diabetes Association currently recommends providing GLP-1a therapy to this patient population independently of glycaemic control. Despite proven clinical benefits, providing GLP-1a to all guideline eligible patients is a significant cost burden on healthcare systems. Therefore, it is imperative to compare the value for money of these agents. Hypothesis: The newly introduced GLP-1a Semaglutide may be cost-saving compared to dulaglutide and liraglutide for preventing MACE in patients with established CVD and T2DM. Methods: We calculated the cost needed to prevent one MACE, by multiplying the annualized number needed to treat to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published RCT data. We performed a sensitivity analysis to mitigate differences between trial populations and other uncertainties. Drug costs were based on published US prices. Results: The cost needed to prevent one MACE with semaglutide is $557,187 ($331,491-$2,194,483) compared to $1,179,360 ($732,888-$2,746,224) with liraglutide and $1,605,904 ($706,044-∞) for dulaglutide. Sensitivity analysis confirmed the advantage of semaglutide. Conclusions: Semaglutide prescribed for secondary prevention of MACE in patients with T2DM and established CVD seems to provide more value for money than dulaglutide and liraglutide for the same purpose.

Introduction: Icosapent ethyl is currently the only drug approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia, who are already on statin therapy. The approved use is both for secondary prevention in patients with established cardiovascular disease (CVD) or primary prevention for patients with diabetes and multiple risk factors. Despite its’ proven clinical benefits, the addition of icosapent ethyl to patient’s current treatment regimens may impose a significant cost burden on healthcare systems. Hypothesis: Prioritizing icosapent ethyl therapy for patients with an established CVD may provide significantly more value for money than when prescribed as primary prevention. Methods: We performed an analysis of the cost required for icosapent ethyl per achieved outcome when prescribed either for primary or for secondary prevention of MACE. The cost needed to treat (CNT) to prevent one MACE in the REDUCE-IT trial was estimated by multiplying the annualized number needed to treat to prevent one event, by the annual cost of therapy. The market price of icosapent ethyl in the US was estimated as 75% of the US national average drug acquisition cost listing. Results: In the REDUCE-IT population, the figured CNT of Icosapent ethyl provided as primary prevention was $874,500 (95% CI: $349,800-∞) vs. $206,965 (95% CI: $160,325-$294,415) for secondary prevention; P Conclusions: The CNT for patients receiving the drug for primary prevention of MACE was four-fold higher than when provided as secondary prevention. Our findings suggest that icosapent ethyl therapy for patients with an established CVD provides significantly more value for money.

Introduction: Semaglutide, a subcutaneous Glucagon-Like Peptide-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over a subcutaneous injection. The value for money of the oral version for the prevention of MACE is not clear. Hypothesis: Oral semaglutide provides less value for money than subcutaneous semaglutide for the prevention of MACE, but more value for money for the prevention of the single endpoint of cardiovascular mortality (CVM). Methods: We calculated the cost needed to prevent (CNT) one MACE, by multiplying the one-year number needed to treat to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published RCT data. The CNT to prevent one event of the single endpoint of CVM was analyzed as a secondary outcome. We performed a sensitivity analysis to mitigate primary differences between the RCTs. Drug costs were calculated as 75% of the US National Average Drug Acquisition Cost listing in June 2020. Results: The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 is $641,823 ($402,021-$3,533,533) compared to $855,040 (95% CI: $420,840-∞) with oral semaglutide in PIONEER 6. The lower cost of subcutaneous semaglutide was confirmed in a sensitivity analysis simulating the effects of the drugs in both RCTs. The CNT to prevent one CVM with semaglutide is $16,342,560 ($2,020,704.00-∞) compared to $1,315,720 (95% CI: $921,004-$8,392,414) with oral semaglutide. Conclusions: Subcutaneous semaglutide prescribed for the prevention of MACE in patients with T2DM is moderately cost-saving compared to oral semaglutide for the same purpose. However, for the prevention of CVM, the oral version provides significantly better economic value.

Introduction: The AHA 2020 strategic goal of reducing CV mortality by 20% was partially achieved (15% reduction 2011-2019). Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 inhibitor and oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, both significantly reduce the incidence of cardiovascular mortality (CVM) in patients with type 2 diabetes (DM) and established CVD. However, the addition of either drug to current diabetes treatment regimens may impose a significant burden on healthcare systems. Hypothesis: Empagliflozin provides more value for money than oral semaglutide for the prevention of CVM in patients with DM. Methods: We calculated the cost needed to treat (CNT) to prevent one case of CVM using either drug, by multiplying the annualized number needed to treat (NNT) to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published randomized controlled trials (RCT) data. We performed a sensitivity analysis to mitigate the primary differences between the RCTs and other uncertainties. Drug costs were calculated as 75% of the US National Average Drug Acquisition Cost listing in June 2020. Results: The annualized NNT of empagliflozin in EMPA-REG-OUTCOME was 141 (95% CI: 104-230) versus 140 (95% CI: 98-893) for oral semaglutide in PIONEER 6, while the corresponding annual costs are $4,572 versus $6,680. Therefore, the CNT of empagliflozin was $644,652 ($475,488-$1,051,560) compared to $935,200 (95% CI: $654,640-$5,965,240) with oral semaglutide. The lower CNT of empagliflozin was confirmed in a sensitivity analysis. Conclusions: The annualized NNT of empagliflozin and oral semaglutide prescribed for the prevention of CVM in patients with T2DM and established CVD is similar. Therefore, the lower cost of empagliflozin results in a lower CNT and better value for money.

Background Icosapent ethyl (IPE) is approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia. However, due to budget constraints, access to IPE will inevitably be limited to a fraction of eligible patients. To help maximize value for money spent, we estimated the number of preventable MACE when providing IPE for primary versus secondary prevention. Methods The number of preventable MACE was estimated by dividing the available budget by the cost needed to treat (CNT) to prevent one MACE. CNT was calculated as the product of the number needed to treat (NNT) to prevent 1 MACE by therapy cost. NNT values were determined according to the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) results. The budget limit was set as the United States’ threshold suggested by the Institute for Clinical and Economic Review. Sensitivity analysis was performed regarding the cost of IPE in the United States. Results The NNT to prevent 1 MACE over 4.9 years in the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial primary prevention cohort was 59 (95% confidence interval [CI]: 24-∞) versus 14 (11-21) for secondary prevention. At an annual IPE cost of $2915, the CNT to prevent 1 MACE was $842,726 (95% CI: $342,804-∞) and $199,969 ($157,118-$299,953) accordingly. A total of $819 million worth of IPE can avoid 4762 MACE (95% CI: 0-11,707) versus 20,069 (13,379-25,541), when provided as primary versus secondary prevention therapy; P Conclusions Prioritizing IPE therapy for patients with an established cardiovascular disease may provide significantly more value for money than primary prevention.

BACKGROUND We evaluated the impact of flash continuous glucose monitoring (FCGM) on glycemic control and healthcare burden in a large real-world cohort of patients with type 1 diabetes (T1D) initiating FCGM technology. METHODS In this retrospective cohort study, we included adults (age ≥18 years) with T1D from a large Health Maintenance Organization in Israel, who initiated FCGM during 2018. Primary outcomes included change in HbA1c ≥3 months following FCGM commencement and change in rate of internal-medicine hospitalization. Additional outcomes included changes in glucose test strip purchases, diabetes related outpatient health care visits and hospitalization for diabetic ketoacidosis (DKA) and/or severe hypoglycemia. RESULTS The study included 3490 patients, followed for a median of 14 (inter-quartile range 11-15) months after FCGM commencement. Among 2682 patients with an HbA1c measured both at baseline and ≥3 months after FCGM initiation, average HbA1c declined from 8.1% ± 1.46% to 7.9% ± 1.31% (P

Background In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. Methods We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Results Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. Conclusion The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers.

Direct oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation but may result in serious bleeding complications. Off-label dose-reduced use of DOACs to mitigate bleeding is common in routine clinical practice although data about its consequences on patient outcomes are limited. Therefore, our objective was to evaluate the effectiveness and safety of off-label dose-reduced vs per-label standard-dose DOAC treatment.The study cohort included newly diagnosed patients with nonvalvular atrial fibrillation that had initiated DOAC therapy between 2011 and 2017 in Clalit Health Services (Tel Aviv, Israel). Effectiveness was defined as the composite outcome of all-cause mortality, stroke, or myocardial infarction. The safety outcome was defined as bleeding events requiring hospitalization. Patients were followed until March 30, 2018 or until occurrence of an outcome event. Hazard ratios (HR) were adjusted for 21 variables, including comorbidities, concomitant medications, and socioeconomic factors, using multivariate regression.A total of 8425 patients met the study criteria; 5140 (61%) patients were treated with DOACs at per-label dosing and 3285 (39%) patients were treated with off-label dose-reduced DOAC. Off-label dose-reduced treatment was associated with a higher rate of the composite effectiveness outcome: adjusted HR 1.57 (95% confidence interval, 1.34-1.83; P.001) and a higher rate of bleeding: adjusted HR 1.63 (95% confidence interval, 1.14-2.34; P = .008).Almost 4 of 10 patients were treated with off-label dose-reduced DOAC, which was associated with reduced effectiveness without a safety benefit. Compliance with per-label dosage may significantly improve outcomes of this population.

e12587 Background: In the phase 3 TAILORx study, the first invasive disease-free survival event (in all arms) was often opposite BC or other second primary cancer. Our goal was to investigate differences in the 21-gene RS results between the primary BC and a second primary BC, as well as the association with clinicopathological characteristics. Methods: This analysis of the prospectively-designed CHS registry included all CHS pts with estrogen receptor (ER)+ HER2-negative BC who underwent RS testing between 1/2006 and 6/2019 and for whom ≥2 RS results were identified which were > 1 year apart. Results: Of the 10,244 RS assays ordered in this time frame, 371 involved pts for whom the assay was performed at least twice. Our analysis focused on the 42 pts for whom the assays were performed > 1 year apart. All pts were females; 76% were initially diagnosed with node-negative BC; median (interquartile range [IQR]) age at first diagnosis was 56 (43-64) yrs. Tumor characteristics for the first and subsequent primary BC are presented (Table). The median time (IQR) between the first and latest RS assay was 4.5 (2.9-6.4) yrs. In 28 pts (67%), the latest primary BC was ipsilateral and in 14 (33%) it was contralateral. The median (IQR) difference between the first and latest RS value was 7 (1-12). The second/third primary BC had higher RS than the first BC in the majority (76%) of pts. Higher RS in the latest primary BC (compared to the first primary BC) was more common when the latest primary BC was ipsilateral than when it was contralateral (86% vs 57%, P= 0.04). Conclusions: In ER+ HER2-negative BC pts, second/third primary BC is generally associated with higher RS result (compared to the first primary BC), particularly if the later primary BC is ipsilateral. [Table: see text]

Evolocumab and ezetimibe, were both proven to significantly reduce the incidence of major adverse cardiovascular events (MACE), in type 2 diabetes patients with atherosclerotic cardiovascular disease and low-density lipoprotein (LDL) cholesterol >70 mg/dl despite statin therapy. Providing evolocumab for all such patients may be a significant burden on healthcare systems. Therefore, we analyzed the treatment cost of ezetimibe versus evolocumab to prevent 1 MACE. We extracted the number needed to treat (NNT) with evolocumab or with ezetimibe for avoiding MACE from the published FOURIER and IMPROVE-IT trials respectively. Drug costs were based on 2018 US prices. Sensitivity and scenario analyses were performed to overcome variances in terms of population risk, efficacy of therapies, and costs. In FOURIER, the 1-year NNT for avoiding MACE with evolocumab was 104 (95% confidence intervals [CI] 66 to 235). In IMPROVE-IT, the 1-year NNT with ezetimibe was 124 (95% CI 73 to 288). The annual cost of evolocumab and ezetimibe is $6,540 and $88, respectively. Therefore, the cost to prevent 1 MACE in the FOURIER and IMPROVE-IT trials would have been $678,981 (95% CI $429,810 to $1,537,910,149) and $10,870 (95% CI $6,384 to $25,322), respectively. Ezetimibe was consistently a cost-saving strategy compared with evolocumab, in all analyses performed, except for the case where evolocumab price is significantly reduced and the branded ezetimibe is used. In conclusion, treatment with ezetimibe seems to be a major cost-saving strategy for preventing MACE in this patient population.

Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 and Liraglutide, a glucagon-like peptide 1 analogue, were both proved to significantly reduce the incidence of cardiovascular (CV) death in patients with type 2 diabetes and established CV disease. However, addition of either drug to current diabetes treatment regimens may impose a significant burden on healthcare systems. We performed a cost-minimization analysis of Empagliflozin versus Liraglutide for preventing CV death. Rates of prevention of CV death were extracted from the published data of the EMPA-REG OUTCOME and LEADER trials. Drug costs were extracted from the US National Average Drug Acquisition Costs of 2017. In the EMPA-REG OUTCOME trial 5,833 patient-years of treatment with Empagliflozin resulted in the prevention of 51 CV deaths. In LEADER, 16,338 patient-years of Liraglutide resulted in the prevention of 59 CV deaths. The price in 2017 of annual Empagliflozin and Liraglutide therapy was $4,980 and $9,300, respectively. Therefore, the cost of Empagliflozin or Liraglutide needed to prevent 1 CV death would be $569,526 (95% confidence interval $415,713 to $921,798) and $2,575,312 (95% confidence interval $1,607,526 to $7,807,986), respectively. In conclusion, use of Empagliflozin for preventing CV death in type 2 diabetes patients with an established CV disease seems to be a major cost-saving strategy compared with Liraglutide. These results should be considered in the context of other individual drug and patient factors.

Background The European Society for Medical Oncology published in 2015 its Magnitude of Clinical Benefit Scale (ESMO-MCBS) for cancer medicines. Our objective was to evaluate the association between Israel's national reimbursement decisions regarding novel cancer drugs, prior to the availability of ESMO-MCBS, and the later published ESMO-MCBS scores. Research design and methods ESMO-MCBS scores were obtained retrospectively for the cancer drugs that were candidates for reimbursement in Israel in 2013-2015 and were categorized to 'highest benefit' (ESMO-MCBS 4-5 or A) 'medium benefit' (3 or B) and 'lowest benefit' (0-2 or C). The reimbursement decisions were accessed and compared with the categorized ESMO scores. Results ESMO-MCBS score was available for 19/22 drugs approved for reimbursement and 15/16 non-approved drugs. 58% of the approved drugs gained a 'highest benefit' score and 37% were 'medium benefit'. 87% of the non-approved drugs had 'lowest benefit' scores. Median score for approved drugs was 4 vs. 1 for the non-approved (p Conclusions The Israeli decisions regarding reimbursement of novel cancer drugs, demonstrated concordance with ESMO-MCBS scores. Incorporation of ESMO-MCBS data in reimbursement deliberations could assist in framing the appropriate use of the limited resources to deliver effective and affordable cancer care.

Background: The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown in the PARADIGM-HF trial to be superior to enalapril in reducing the risks of cardiovascular (CV) deaths and hospitalizations in heart failure (HF) patients. Although several studies suggested that sacubitril/valsartan is a cost-effective therapy, budget constraints may limit its use. Our objective was to characterize HF sub-populations in which cost per CV death/hospitalization prevented are excessively high in order to assist in treatment prioritization decisions. Methods: Outcome data were retrieved from the published PARADIGM-HF trial reports. Costs were calculated based on current United States prices of sacubitril/valsartan. Results: In the PARADIGM-HF trial, treatment of 4,187 patients with sacubitril/valsartan resulted in prevention of 203 CV deaths or HF hospitalizations (135 CV deaths) during a total of 9,396 patient-years. The estimated additional cost of sacubitril/valsartan during the trial’s follow-up period would have reached $42,089,220. Therefore, the cost of preventing one HF hospitalization or CV death would have been $207,336 and the cost of preventing one CV death would have been $311,772. This figure is significantly higher in sub-groups that presented a lower risk-reduction, as in patients with an ejection fraction >35% ($674,831) and in patients without prior use of HF medical therapy ($2,024,494). Conclusions: In healthcare settings under budget constraints, payers can maximize clinical outcomes in HF patients, by prioritizing sacubitril/valsartan therapy to sub-populations that have demonstrated higher benefit in the PARADIGM-HF trial. Advocating the reduction of sacubitril/valsartan prices could enable wider populations to benefit from this promising therapy.

After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear.To evaluate 'real-life' outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice.Using the computerized administrative database of Clalit Health Services' (CHS), Israel's largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS' patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates.Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77).In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from 'real-life' practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.

6591 Background: Observational studies have shown an increased risk of BC with use of HRT. However, data on the prognosis of BC that develop in HRT users are inconsistent. The association between HRT use and results of the 21-gene Recurrence Score (RS) assay (Oncotype DX, Genomic Health Inc.) has not been investigated. We aimed to analyze this association, and examine the actual rate of distant recurrence or death in this population. Methods: Clalit Health Services (CHS) is the largest health maintenance organization (HMO) in Israel. We identified all CHS newly diagnosed ER+, N- breast-cancer patients, aged 45-60 that performed a RS assay between 01/2006-12/2012 and that were treated for at least three months with HRT during the eight years before BC diagnosis. A 1:4 matched-cohort analysis was performed, with matching made according to age and year of BC diagnosis. Clinical and demographic data were extracted from the CHS centralized registry for all patients. RS assay scores was grouped according to the TAILORX categorization and distribution was compared using Chi-square test. Kaplan-Meier analysis with log-rank test was performed in order to compare time to a combined outcome of distant-recurrence and mortality. Results: A cohort of 259 HRT-treated patients was identified and matched with 1001 controls, not treated with HRT. The proportions of low-risk patients (RS 0-25) and high-risk patients (RS 26-100) were 76.8% and 23.2%, respectively, within HRT-treated patients, and 80.4% and 19.6% within controls. Chi square test was not found significant (χ2= 1.634, p = 0.201). The mean follow-up time was 148.4 months for the cases and 146.9 months for controls, with log-rank test not showing a significant difference between groups. Conclusions: These data did not show significant association between HRT use and higher RS assay scores, and also did not find an association between HRT use and actual distant recurrence or death. Although the proportion of patients with high risk RS appeared to be slightly higher within HRT treated patients, this difference had not reached significance and further studies are required.

6608 Background: Advanced NSCLC is associated with an increased risk for VTE, with a reported rate of 8-15%. Clinical observations suggest a higher rate of VTE in patients with ALK-rearranged NSCLC. Clalit Health Services (CHS) is both a healthcare payer and provider, covering over 50% of the population in Israel, with individual patient data recorded in a centralized electronic database. We aimed to determine the incidence of VTE in patients with ALK-LC using a population-based cohort. Methods: We identified all patients diagnosed with NSCLC between 01/2012-12/2017 within CHS. Clinical and demographic data (including VTE risk factors, i.e. components of the Khorana score) were extracted from the CHS registry for all patients. Patients with ALK-LC were identified according to crizotinib prescriptions (dispensed after an approved CHS' pre-authorization for an ALK-LC diagnosis). VTE was identified by ICD diagnosis codes 415.xx, 444.xx, 451.xx and 453.xx. VTE risk factors (Khorana score) were also extracted. Association between ALK-LC and VTE were analyzed using logistic regression, estimating univariate and multivariate Odds Ratios (OR). Results: Overall, 4327 patients with a diagnosis of NSCLC were identified. 149 (3%) had at least one prescription for crizotinib for advanced ALK-LC. The rate of VTE in these patients was 25% (38 of 149 patients), while in the non-ALK-LC the rate was 14% (596/4178), OR = 2.05, p = 0.0004. The association was significant also in a multivariate analysis adjusting for, age, smoking status, BMI, platelet count, hemoglobin and Charlson co-morbidity score (OR 1.66, p = 0.018). Conclusions: This pooled analysis of individual patient data confirms prior data from smaller retrospective studies, suggesting ALK-LC is associated with a high risk of VTE. Randomized trials with prophylactic anti-coagulation are unlikely to be performed in this rare subtype, thus increased awareness and consideration of VTE prophylaxis in high risk patients is warranted.

Objectives Nivolumab has recently received regulatory approval as a 2nd-line treatment of non-small cell lung cancer (NSCLC). The data regarding its effectiveness and safety in real life setting is lacking. Materials and methods 260 consecutive patients with advanced NSCLC treated with nivolumab at five Israeli cancer centers between January 2015 and March 2016 were evaluated for overall survival (OS) and toxicity. OS was analyzed by the Cox proportional-hazards regression model. Overall response rate (ORR) and progression-free survival (PFS) were assessed in 49 patients using RECIST, v.1.1. Results Median age was 67y (41–99); males 68%; smokers 76%; ECOG PS ≥2 46%; non-squamous/squamous/other/NR 70%/23%/6%/1%; brain metastases 21%; liver metastases 21%; treatment line: 1st/2nd/3rd+-line/NR 6%/64%/26%/4%. With median survival follow-up of 18.5 months (range, 12.0–26.9), 155 (60%) patients died; median OS comprised 5.9 months (95% CI 4.7–7.4). In univariate and multivariate analysis, the only variable which significantly correlated with OS was ECOG PS. Median OS of patients with ECOG PS 0/1 and ECOG PS ≥2 comprised 9.5 months (95% CI, 6.7-NR) and 3.5 months (95% CI, 2.6–4.5), respectively. For 49 patients evaluable for response (median follow-up of 8.4 months (range, 2–16.8), ORR was 35%, median PFS was 2.8 months (95% CI, 1.8–7.7), incidence of pseudo-progression was 9%. The nivolumab safety profile was in accordance with the literature data, except for febrile neutropenia and pericarditis (observed in 1 case each). Conclusion In real life setting, the effectiveness of nivolumab is reasonable yet less prominent than it has been demonstrated in clinical trials. ECOG PS ≥2 is associated with poor prognosis.

Background/Objectives Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can significantly lower low-density lipoprotein (LDL) cholesterol levels. Early evidence suggests that use of PCSK9i also reduces the incidence of major adverse cardiovascular events (MACE). Our objective was to determine preliminary economic implications of PCSK9i use to avoid MACE, based on the current data from major phase III clinical trials. Methods Outcome data of the 4529 patients treated with PCSK9i in the OSLER and ODYSSEY LONG TERM trials were collected from the published reports. Cost of preventing MACE was evaluated based on the existing outcome data and current US prices of PCSK9i. The pooled results were compared to the cost of curing Hepatitis C Virus (HCV) patients with novel HCV drugs. Results PCSK9i treatment in the OSLER and ODYSSEY LONG TERM trials resulted in prevention of 35 MACE in a total of 4903 patient-years: 8 cardiovascular deaths, 22 myocardial infarctions, 0 strokes and 5 unstable anginas. The cost of PCSK9i drugs consumed during the trial's current follow-up period, could have reached $70,172,141. Therefore, the cost of preventing any MACE would be $2,004,918 and the cost of preventing one death would be $8,777,518. These figures are one hundred fold higher than the cost of curing one HCV patient (~$84,000). Conclusions According to the current published data, using PCSK9i to prevent MACE seems to be a very expensive strategy. If upcoming outcome trials will demonstrate similar results, it seems that at current prices, using these drugs would not be affordable for most healthcare systems.

Backgound Randomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates. Methods We performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3 year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment. Results 18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6–4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7–4.7) in dabigatran patients, and 4.1 (95% CI, 3.0–5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56–0.90) for warfarin, 0.4 (95% CI, 0.18–0.87) for dabigatran, and 0.27 (95%CI, 0.10–0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62–2.20) for warfarin, 2.98 (95% CI, 2.4–3.5) for dabigatran and 2.39 (95%CI, 1.6–3.5) for rivaroxaban. Conclusions We demonstrate similar bleeding rates with both dabigatran 150 mg and 110 mg and rivaroxaban compared to warfarin.

The abundant use of antibiotics (Abs) in the community plays a major role in inducing Ab resistance, but the literature concerning patterns in outpatient Ab use is limited. This study aims to lay the foundations for future policy and interventional programs to address the rise in Ab resistance by looking at long-term trends in Ab usage in Israel. Defined daily doses per 1,000 inhabitants per day (DID) of total Ab use, consumption in different age groups, and of different Ab preparations were calculated for the years 2000, 2005, and 2010 in the eight districts of Israel. Data were collected from the pharmacy registries of “Clalit Health Services”, the largest Health Maintenance Organization (HMO) in Israel, covering 4 million patients, representing 53 % of the population. Trends in use over time were analyzed. The overall Ab usage in Israel has remained constant in the last decade. Three significant trends were identified in this study: an increase in the consumption of expensive, broad-spectrum Abs, paralleled by a reduction in narrow-spectrum Abs; an increase in Ab consumption among the elderly, counteracted by reduced usage among children; large regional variations in the overall and specific use of Ab agents. Our main findings of increased broad-spectrum Ab consumption, primarily among the adult population in Israel, and a wide variability in Ab use between the regions in Israel, can focus our future studies on searching for the factors behind these trends to aid in constructing interventional methods for decreasing outpatient Ab overuse.

ObjectivesRisk-sharing is being considered by many health care systems to address the financial risk associated with the adoption of new technologies. We explored major stakeholders' views toward the potential implementation of a financial risk-sharing mechanism regarding budget-impact estimates for adding new technologies to the Israeli National List of Health Services. According to our proposed scheme, health plans will be partially compensated by technology sponsors if the actual use of a technology is substantially higher than what was projected and health plans will refund the government for budgets that were not fully utilized.MethodsBy using a semi-structured protocol, we interviewed major stakeholders involved in the process of updating the National List of Health Services (N = 31). We inquired into participants' views toward our proposed risk-sharing mechanism, whether the proposed scheme would achieve its purpose, its feasibility of implementation, and their opinion on the other stakeholders' incentives.ResultsParticipants' considerations were classified into four main areas: financial, administrative/managerial, impact on patients' health, and influence on public image. Most participants agreed that the conceptual risk-sharing scheme will improve the accuracy of early budget estimates and were in favor of the proposed scheme, although Ministry of Finance officials tended to object to it.ConclusionsThe successful implementation of risk-sharing schemes depends mainly on their perception as a win-win situation by all stakeholders. The perception exposed by our participants that risk-sharing can be a tool for improving the accuracy of early budget-impact estimates and the challenges pointed by them are relevant to other health care systems also and should be considered when implementing similar schemes.

Objective Onco type DX, a 21-gene assay, was clinically validated as a predictor of 10-year recurrence-free survival and treatment response in patients with early-stage estrogen-receptor-positive, lymph-node negative breast cancer (ER+ LN- ESBC). This study determined "real-life" alteration in treatment decision and economic implications of Onco type DX use in women with ER+ LN- ESBC. Methods Clalit Health Services (CHS, Tel Aviv, Israel), determined the proportion of women in low, intermediate and high-risk groups in the first 368 Onco type DX assays performed, the change of adjuvant therapy recommendation following the recurrence (RS) results from Onco type DX use, and associated chemotherapy costs. The risk of recurrence-free survival was derived from prespecified statistical protocols of NCI-sponsored trials conducted by NSABP (B-14 and B-20). Utilities were literature based. A 3% discount rate was employed. Results Onco type DX altered recommendations of 40% of patients, 84% of whom were changed from hormone + chemotherapy to hormonal therapy alone. Among high-risk women, 8% switched actual treatment from hormonal therapy to hormone + chemotherapy. By reducing the chemotherapy disutility, quality-adjusted life-years (QALY) increased 0.170 years. Use of Onco type DX costs $10,770 per QALY gained. Sensitivity analyses revealed that risk reduction in the low-risk population, the cost of adverse events, and the relative risk reduction of recurrence were the most influential variables. Conclusion Onco type DX resulted in net QALY gain and increased overall costs, with an incremental cost-effectiveness ratio of $10,770. For CHS, Onco type DX represents an effective and affordable approach to favorably affect the lives of women with ESBC.

Importance The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. Objective To describe the risk for HZ in patients with psoriasis and its relation to treatment. Design, Setting, and Participants A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95 941 patients with psoriasis in the analysis, with 522 616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. Main Outcomes and Measures Incidence of HZ associated with systemic therapies. Results In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). Conclusions and Relevance Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Background The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice. Methods All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services’ (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model. Results 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5–16.5) vs. 31.0 for TBP (95% CI: 20.6–41.4), P

e12512 Background: Tumors with HER2 overexpression usually respond to HER2-targeted therapies. Since the CLEOPATRA and EMILIA trials, a taxane plus trastuzumab and pertuzumab (TTP) are the first-line standard for the management of HER2 + metastatic breast cancer (MBC) and trastuzumab emtansine (TDM-1) is the second-line standard. Intrinsic subtypes existing within HER2+ tumors may impact the degree of a patient’s response to anti HER2 therapy; however HER2 subtyping for predicting response is still experimental and not in routine clinical use. In this retrospective population-based study, we aimed to assess whether duration of treatment (DOT) of second-line TDM1 is associated with the DOT of first-line TTP, and might serve as a hint for a HER2 subtype. Methods: Clalit Health Services (CHS) manages health care of 52% of the Israeli population. We identified 113 HER2+ CHS MBC patients, treated with TTP as first-line treatment that initiated TDM1 as second-line, until Dec. 31, 2016. Patient's (pts) demography, HER2 and HR status were recorded. A Cox proportional hazard model, stratified by HR status, adjusted for age and prior adjuvant trastuzumab, was used to explore the association between second-line and first-line DOT in HR positive and negative pts. Results: Pts baseline characteristics and DOT in first- and second-line treatment are presented in the table. A statistically significant association between DOT of both treatment lines was found in HR positive pts with a trend also in HR negative pts. Conclusions: The observed association between first- and second-line DOT, unrelated to hormonal status, may result from a primary characteristic of the intrinsic tumor subtype, that impacts acquired resistance. Longer observations in larger patient cohorts are required to confirm this observation. [Table: see text]

INTRODUCTION Recent large randomized controlled trials have shown that direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation (AF) and are associated with similar or lower rates of bleeding. The results for bleeding seen in Phase 3 trials might not be applicable to real world practice. Population-based studies suggest that the bleeding risk for DOACs and VKA is similar however neither the risk of bleeding associated with different doses of DOACs nor that associated with apixaban in routine clinical practice is well established. We performed a large population-based study to determine the incidence of bleeding in patients with AF beginning treatment with different doses of dabigatran, rivaroxaban, apixaban or a VKA. METHODS From the computerized database of the 4.5 million member Israeli Clalit Health Services health care provider, consecutive patients initiating a VKA or DOAC for AF between January 1, 2011 and December 31, 2014 were studied. Bleeding patients who required hospitalization were identified and key clinical and laboratory data were recorded. Incidence of bleeding was calculated during the first 20 months of treatment which was the minimum duration of treatment for all of the drugs. Adjusted hazard ratios for overall bleeding, intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding and all-cause mortality within 30 days were recorded and case fatality rates were calculated as the proportions of bleeding patients who died within 30 days. RESULTS 26184 patients initiated anticoagulants for AF: 14258 received VKA, 214 -received dabigatran 75 mg, 3563 received dabigatran 110 mg , 1410 received dabigatran 150 mg, 2570 received rivaroxaban 15 mg, 2140 received rivaroxaban 20 mg, 1227 received apixaban 2.5 mg and 802 received apixaban 5 mg. Key patient demographics and the overall and site-specific bleeding rates are shown in table 1. Hazard ratios for any bleeding, ICH and GI bleeding adjusted for age, renal failure, CHADS2 score, aspirin use and Charlson comorbidity score favored dabigatran 150 mg versus VKA (P CONCLUSIONS The results of our population-based non-randomized study of unselected AF patients demonstrate a decreased bleeding rate for dabigatran 150mg and an increased bleeding rate for apixaban 2.5 mg compared to VKA. There was a consistent tendency for increased bleeding in patients receiving lower versus higher doses of the NOACs which probably reflects physician tendency to select lower doses of DOACs for patients at greater risk for bleeding. Disclosures Ellis: Boehringer Ingelheim: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau. Eikelboom:Pfizer: Honoraria, Research Funding; Eli Lilly: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Bristol Myer Squibb: Honoraria, Research Funding; Sanofi-Aventis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Background Previous studies suggest that cancer-related interventions are valued by policy makers more favorably than interventions for other medical conditions, but the views of practicing physicians have not yet been assessed in Israel. Attitudes and judgments of practicing physicians may assist decision-makers in their deliberations on coverage of new technologies. We conducted a national survey in Israel among oncologists and family physicians to explore their views on access to care, coverage decisions and treatment recommendations for cancer and congestive heart failure (CHF) patients. Methods We administered a web-based survey to 300 family physicians and 156 oncologists. The questionnaire included 24 statements and physicians were asked to indicate their level of agreement with each statement on a 5-point Likert scale, ranging from “strongly agree” to “strongly disagree”. Where relevant, physicians were asked to express their views on interventions for cancer and CHF respectively. Results Response rates were 39% for family physicians and 36% for oncologists. Participants expressed similar views on cancer and CHF care and no significant differences were found between the two medical specialties. More than 85% of physicians believe that inclusion of a treatment in the National List of Health Services (NLHS) strongly affects their patients’ access to care. Approximately 80% suggest that more use of comparative-effectiveness and cost-effectiveness analysis is needed in coverage decisions. The vast majority of respondents (75%) suggest that assessment of value-for-money should be made by an independent (academic) institution or the national committee responsible for recommending coverage decisions, Seventy percent believe that treatments not included in the NLHS should be included in supplementary health insurance programs and only a small minority of respondents (

e18258Background: The Israeli Health Insurance Law stipulates a National List of Health Services (NLHS) which all residents are entitled to. Every year, the government allocates an additional budge...

6518Background: In the United States, the addition of bev to 1st-line chemotherapy in mCRC provides an additional 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,240/QALY (Goldstein et al. Journal of Clinical Oncology, 2015). However, this estimate of value is not transferrable between countries due to variable international pricing strategies. Our objective was to establish the cost-effectiveness of bev in mCRC in 5 different countries: the US, the UK, Canada (CAN), Australia (AUS), and Israel (ISR). Methods: We performed the analysis on the basis of a previously published Markov model (Goldstein et al. JCO, 2015). Input data for efficacy, adverse events and quality of life were considered to be standard for all countries. We used country specific prices for all healthcare services, medications, and administration costs. For the UK, all costs were obtained from UK Department of Health, National Health Service and British National Formulary. For CAN, all ...

539 Background: Based on a single phase 3 study, the mTOR inhibitor tem was approved as 1st line therapy for prmRCC. However, in daily practice, prmRCC pts are often treated with the VEGFR and PDGFR inhibitor su. We aimed to compare the clinical effectiveness of su vs tem in prmRCC pts. Methods: We performed an international multicenter retrospective study of pts with prmRCC (HENG criteria), who were treated in 8 centers across 2 different countries. 31 pts were treated with 1st line tem. Each tem treated pt was individually matched with a 1st line su treated pt, by clinicopathologic factors. The effect of tx type (tem vs su) on clinical benefit, progression free survival (PFS) and overall survival (OS), was tested using a chi-square test and partial likelihood test from cox model. Furthermore, univariate and multivariate analyses of association between clinicopathologic factors and tx type (tem vs su), and outcome were performed using the entire pt cohort (n=62). Results: The groups were matched by age (median 65), gender (male 68%), prior nephrectomy (58%), renal cell carcinoma histology (clear cell 81%), smoking status (active in 35%), use of angiotensin system inhibitors (42%), and pre-tx neutrophil to lymphocyte ratio >3 (58%). In tem vs su treated pts, clinical benefit (partial response + stable disease) was 61% (n=19) (partial response 6%, n=2) vs 71% (n=22) (partial response 29%, n=9) (p=0.62). Median PFS was 5 vs 8 mos (p=0.08), and median OS 9 vs 17 mos (p=0.03). In multivariate analyses of the entire pt cohort (n=62), su tx was independently associated with OS (HR 0.6, p=0.001). Conclusions: In prmRCC patient, the VEGFR inhibitor su may be associated with an improved outcome vs the mTOR inhibitor tem.

As part of the process of updating the National List of Health Services in Israel, health plans (the ‘payers’) and manufacturers each provide estimates on the expected number of patients that will utilize a new drug. Currently, payers face major financial consequences when actual utilization is higher than the allocated budget. We suggest a risk-sharing model between the two stakeholders; if the actual number of patients exceeds the manufacturer’s prediction, the manufacturer will reimburse the payers by a rebate rate of α from the deficit. In case of under-utilization, payers will refund the government at a rate of γ from the surplus budget. Our study objective was to identify the optimal early estimations of both ‘players’ prior to and after implementation of the risk-sharing scheme. Using a game-theoretic approach, in which both players’ statements are considered simultaneously, we examined the impact of risk-sharing within a given range of rebate proportions, on players’ early budget estimations. When increasing manufacturer’s rebate α to be over 50 %, then manufacturers will announce a larger number, and health plans will announce a lower number of patients than they would without risk sharing, thus substantially decreasing the gap between their estimates. Increasing γ changes players’ estimates only slightly. In reaction to applying a substantial risk-sharing rebate α on the manufacturer, both players are expected to adjust their budget estimates toward an optimal equilibrium. Increasing α is a better vehicle for reaching the desired equilibrium rather than increasing γ, as the manufacturer’s rebate α substantially influences both players, whereas γ has little effect on the players behavior.

Background Previous studies have reported an association between antipsychotic medications and diabetes. Objective To explore the association between antipsychotic medications and diabetes in patients of different ages. Methods A retrospective analysis of a large health maintenance organization's drug claim database (3.7 million members) was performed. All patients treated with antipsychotic drugs during 1998–2004 were identified. Patients with diabetes were defined by a record of antidiabetic drug uso during 2004. The prevalence of diabetes in different age groups treated with antipsychotics was compared with the prevalence of diabetes among enrollees in the same age groups not treated with antipsychotics. Results: Among 82,754 patients treated with antipsychotics, the association between diabetes and consumption of antipsychotics was strongest in the younger age groups and decreased with increasing age: for patients aged 0–24 years, OR 8.9 (95% CI 7.0 to 11.3); 25–44 years, OR 4.2 (95% CI 3,8 to 4.5); 45–54 years, OR 1.9 (95% CI 1.8 to 2.1); 55–64 years, OR 1.3 (95% CI 1.2 to 1.4); and 65 years or older, OR 0.93 (95% CI 0.9 to 1.0). However, the risk associated with atypical antipsychotics was lower than the risk associated with typical antipsychotics, with ORs ranging from 0.7 in patients 0–24 years old to 0.3 in those 65 years or older. Conclusions: Antipsychotic drug use was associated with diabetes mellitus. This association was stronger in younger patients. In older adults, the difference was much smaller and, in some cases, there was no association. A lowor risk was associated with atypical agents, as compared with typical antipsychotics. Clinicians should bo aware that young adults treated with antipsychotics are at increased risk for diabetes.